2095 lines (2094 with data), 514.6 kB

Treatment with systemic immunostimulatory agents (including, but not limited to, interferon-alpha or interleukin-2 [aldesleukin]) within 6 weeks prior to cycle 1, day 1.
Patient with advanced or metastatic solid tumor and has disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to treatment that meets the following requirements for the part of the study they will participate in:
Must have failed treatment with one regimen containing a fluoropyrimidine, oxaliplatin with or without bevacizumab for metastatic disease. All patients must have received a minimum of 6 weeks of the first-line regimen that included bevacizumab (if applicable), oxaliplatin and a fluoropyrimidine in the same cycle. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy.
Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of napabucasin or while undergoing treatment with FOLFIRI and for 180 days after the last dose of FOLFIRI.
Prior treatment with napabucasin.
The patient must be willing to undergo a biopsy prior to treatment
Prior treatment with TRC105
Current treatment or participation on another therapeutic clinical trial
Patients undergoing primary systemic treatment (hormones or chemotherapy) as initial treatment with neoadjuvant reducing tumor size
Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
PRIOR TREATMENT
Patients must have adequate hematologic, liver and renal function =< 28 days prior to randomization\r\n* NOTE: It is preferred that laboratory values for eligibility be assessed after the last dose of prior treatment, especially in cases where most-recent treatment prior to study entry is chemotherapy
Patients may not be receiving Coumadin while on treatment; other anticoagulants are allowed
No currently active other malignancies which require systemic treatment
Any prior chemotherapy or androgen receptor (AR)-directed therapy for CRPC, (e.g. docetaxel, cabazitaxel, mitoxantrone, abiraterone acetate, ketoconazole, or enzalutamide); previous treatment with radium-223 or sipuleucel-T is allowed
Patients with prior treatment with PLD
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
No more than 3 prior systemic treatment regimens for advanced PNET
Treatment with systemic immunostimulatory medications (including, but not limited to interferon [IFN]-alpha or interleukin [IL]-2 within 42 days prior to randomization
Patient has not had prior treatment with blinatumomab
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
Patients with recurrent carcinoma of the vulva regardless of previous treatment
Previous steroid treatment and/or radiation treatment is not allowed unless it is for the emergent management of a mediastinal mass; emergent steroid treatment and/or radiation treatment should stop once protocol therapy is initiated
No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue)
No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process; only one cycle is allowed
Prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) is allowed, provided the following is met: minimum of 6 weeks prior to cycle 1, day 1
Previous treatment with brentuximab vedotin will be allowed if it was done 6 months prior to enrollment and was not refractory to or had progressive disease (PD) on brentuximab vedotin (BV)
Prior treatment with brentuximab in the last 6 months or had refractory or progressive disease to prior BV treatment
At least three weeks since last prior anticancer treatment and adequate recovery from prior treatment toxicity
Prior treatment with PM01183, topotecan or anthracyclines.
Current treatment on another therapeutic clinical trial
Prior treatment with alisertib
Initiation of bisphosphonate/denosumab therapy during protocol treatment; patients on stable doses of bisphosphonates or denosumab which have been started no less than 4 weeks prior to treatment start may continue on this medication; NOTE: initiation of bisphosphonate/denosumab therapy will be allowed for the treatment of osteoporosis or prevention of skeletal-related events (SRE) during protocol treatment
Prior treatment with PM01183 or trabectedin
Uncontrolled ascites requiring weekly large-volume paracentesis for 2 consecutive weeks prior to initiation of study treatment
For Cohort E only: prior treatment with fulvestrant is prohibited
Clinical indication for treatment with azacitidine for MDS or AML.
-  Treatment with an immunomodulatory agent within 4 weeks prior to first administration of BI 836858.
prior treatment failure with at least two cycles of hypomethylating agent.
Prior treatment with an anti-CD123-directed agent
Prior treatment with immunotherapy
Patients must not have received prior treatment with inotuzumab ozogamicin; previous treatment with other anti-CD22 antibodies must have been completed at least 90 days prior to registration
Preceding line of treatment included response to anti-androgen, progression documented after withdrawal of the anti-androgen.
Treatment before study with
Treatment before study with
Patients who have had any prior radiotherapy to the treatment site(s)
Prior pomalidomide treatment (for patients on the pomalidomide arm)
Prior treatment with systemic chemotherapy for bladder cancer. (Prior intravesical treatment is allowed.)
Other prior malignancy active within the previous 2 years except for local or organ-confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
Prior therapy with intravesical Bacillus Calmette-Guerin (BCG) within 6 weeks of treatment.
Receipt of previous approved or investigative immune modulatory agent within 28 days of receiving the first dose of treatment;
Prior treatment with idelalisib;
Past, current or planned treatment with tumor treatment fields; oncolytic viral treatment; or prior exposure to an investigational agent or device within 28 days of receiving the first dose of treatment;
Prior treatment with a BCMA-targeted agent
Any prior ALK inhibition (for screening and treatment phases)
Prior therapy with BRAF/MEK agents within 3 weeks prior to first day of study treatment (for treatment phase)
Any other systemic or regional anticancer therapy (cytotoxic chemotherapy, embolization) within 3 weeks or 1 cycle length, whichever is shorter, prior to first day of study treatment (for treatment phase)
Prior RT or clinically relevant major surgery (e.g. craniotomy, metastasectomy) within 2 weeks prior to first day of study treatment (for treatment phase)
Any serious, active infection at the time of treatment such as bacteremia (for treatment phase)
Prior treatment with venetoclax
Prior treatment with more than 1 cycle of azacitidine or decitabine.
Treatment-naive participants with AML who are >/=75 years old
All Cohort A Dose Escalation Participants:\r\n* Prior hormonal therapy: Participants may have received any number of previous endocrine / hormonal lines of therapy in the metastatic setting (including prior fulvestrant), as long as the last dose is >= 14 days prior to first dose of study treatment\r\n* Prior biologics / investigational therapy: Prior therapy with biologics and investigational drugs is allowed, as long as the last dose is >= 21 days prior to first dose of study treatment\r\n* Prior CDK4/6 inhibition is allowed; participants who have had prior ribociclib must have received treatment at full-dose without any dose reductions; the last dose is required to be >= 21 days prior to first dose of study treatment\r\n* Treatment with prior PD1/PDL1/CTLA4 inhibitors is prohibited\r\n* Prior radiotherapy: Participants may have received radiotherapy for palliative purposes but must have completed treatment ? 14 days prior to first dose of study treatment and not be experiencing grade > 1 treatment-related toxicities\r\n* Evaluable or measurable disease by RECIST 1.1
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior CDK4/6 inhibition is allowed; participants who have had prior ribociclib must have received treatment at full-dose without any dose-reductions; the last dose is required to be >= 21 days prior to first study treatment
Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant): Prior radiotherapy;\r\n* Participants may have received radiotherapy for palliative purposes but must have completed treatment >= 14 days prior to first dose of study treatment and not be experiencing > grade 1 treatment related toxicities
Cohort A Dose Expansion (Ribociclib + PDR001): Prior radiotherapy: \r\n* Participants may have received radiotherapy for palliative purposes but must have completed treatment >= 14 days prior to first dose of study treatment and not be experiencing grade > 1 treatment-related toxicities
Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Prior radiotherapy:\r\n* Participants may have received radiotherapy for palliative purposes but must have completed treatment >= 14 days prior to first dose of study treatment and not be experiencing grade > 1 treatment-related toxicities
Treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents
Prior treatment with a monoclonal antibody or chimeric antigen receptor T cell (CAR-T) infusion for the treatment of AML (CD33 or other target).
For Groups B or C patients must be off conventional therapy for at least 1 week prior to receiving treatment on this study
Inclusion Criteria:\n\n        Specific criteria for patients who continue treatment as well as safety and survival\n        follow-up in the extension study:\n\n          -  Eligible for continuing or crossing over to atezolizumab-based therapy at the time of\n             the parent-study closure as per the parent study or eligible for continuing the\n             comparator agent(s) in a Genentech- or Roche-sponsored study at the time of the\n             parent-study closure as per the parent study\n\n          -  First dose of study treatment in the extension study will be received within the\n             treatment interruption period allowed by the parent study\n\n          -  Continue to benefit from atezolizumab-based study treatment or from the comparator at\n             the time of parent-study closure as assessed by the investigator\n\n          -  Negative serum pregnancy test within 7 days prior to start of study treatment in women\n             of childbearing potential\n\n        Specific criteria for patients who do not continue treatment in the extension study and/or\n        receive commercially available atezolizumab (Tecentriq) outside this extension study and\n        continue safety and survival follow-up only in the extension study:\n\n        - Discontinuation of atezolizumab-based therapy in parent study and in survival follow up\n        at the time of parent study closure, or eligible for continuing or crossing over to\n        atezolizumab-based therapy as per the parent protocol and have access to commercially\n        available atezolizumab (Tecentriq) outside this extension study at the time of the\n        parent-study closure\n\n        Exclusion Criteria:\n\n        Specific criteria for patients who continue treatment as well as safety and survival\n        follow-up in the extension study:\n\n          -  Meet of any of the study treatment discontinuation criteria specified in the parent\n             study at the time of enrollment in the extension study\n\n          -  Study treatment is commercially marketed in the patient's country for the patient\n             specific disease and is accessible to the patient\n\n          -  Time between the last dose of treatment received in parent study and first dose in\n             extension study is longer than the interruption period allowed in the parent study\n\n          -  Treatment with any anti-cancer treatment (other than treatment permitted in the parent\n             study) during the time between last treatment in the parent study and the first dose\n             of study treatment in the extension study\n\n          -  Permanent discontinuation of atezolizumab for any reason during the parent study or\n             during the time between last treatment in the parent study and the first dose of study\n             treatment in the extension study (if applicable)\n\n          -  Any unresolved or irreversible toxicities during the parent study that required\n             permanent discontinuation of study treatment, in accordance to the parent study or\n             local prescribing information\n\n          -  Ongoing SAE(s) that has not resolved to baseline level or Grade less than or equal to\n             (<=) 1 from the parent study or during the time between last treatment in the parent\n             study and the first dose of study treatment in the extension study\n\n          -  Any serious uncontrolled concomitant disease that would contraindicate the use of\n             study treatment at the time of the extension study or that would place the participant\n             at high risk for treatment-related complications\n\n          -  Concurrent participation in any therapeutic clinical trial (other than the parent\n             study)\n\n        Specific criteria for patients who do not continue treatment in the extension study and/or\n        receive commercially available atezolizumab (Tecentriq) outside this extension study and\n        continue safety and survival follow-up only in the extension study:\n\n        - Discontinuation of comparator in parent study and in survival follow-up at the time of\n        parent study closure
Clinical conditions requiring treatment with oral or parenteral anticoagulants or antiplatelet agents unless treatment can be discontinued 7 days (or 5 half-lives) prior to initiation of study treatment (except used as flushes for indwelling catheters)
Refractory to or relapsed after at least 1 prior treatment line.
Prior treatment with MM-310
Refractory to prior brentuximab vedotin (i.e. progression while on treatment)
Ongoing treatment with an anticancer agent.
Previous treatment with Apatinib.
Patients on bisphosphonates may continue receiving bisphosphonate therapy during study treatment
Patients must be willing to donate a small amount of whole blood prior to treatment and during treatment for laboratory analysis
Docetaxel monotherapy is a reasonable treatment in the judgement of the Investigator
Prior treatment with CD47 or signal regulatory protein alpha (SIRP?) targeting agents.
Resolution of treatment-related toxicities
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
Prior treatment with an antiPD1, antiPDL1, antiPDL2, antiCD137, or antiCTLA4 antibody, or any other antibody or drug specifically targeting Tcell co-stimulation or checkpoint pathways.
Subjects have no known curative treatment.
Ongoing treatment with an anticancer agent for MDS not contemplated in this protocol.
Previous treatment with palbociclib
Patients who have had previous treatment with bevacizumab
Are eligible for a curative treatment option.
Previous progression (radiographic or PSA progression) while on treatment with abiraterone, enzalutamide, or a combination.
Recovery from prior treatment-related toxicities
Prior treatment with regorafenib
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Cohort A:\r\n* Prior treatment with at least one regimen containing trastuzumab and taxane\r\n* No prior treatment with T-DM1 that was discontinued due to disease progression or toxicity\r\n* No more than 4 prior lines of therapy in the metastatic setting
Patients have had no previous treatment except corticosteroid use
Research participants with any concomitant significant medical illness that in the investigator’s opinion cannot be adequately controlled with appropriate therapy, or that would impair the evaluation of side effects related to this treatment, alter drug metabolism or the tolerance to this treatment
For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
Must be capable of treatment without general anesthesia
Prior treatment with the same agent or combination as the study drug; prior treatment in monotherapy when treated in one of the combination arms in the study is allowed
No prior systemic treatment is allowed, except for subjects in the phase I cohort who are permitted one prior systemic treatment
Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment
Hematologic growth factors are not allowed at Screening or during the first cycle of treatment.
Any prior treatment with taxotere or carboplatin
Treatment with clarithromycin, anti-myeloma therapy including investigational agents or plasmapheresis within 15 days prior to treatment in this study
Previous treatment with ixazomib or pomalidomide
Prior treatment with radiopharmaceutical including radium-223, strontium-89, or samarium-153
Prior treatment with 3rd generation TKI
Ongoing treatment with an anticancer agent not contemplated in this protocol.
Suitable for treatment with nivolumab per package insert
Prior treatment with a cancer vaccine for this indication
Prior treatment with any methotrexate containing systemic regimen within 1 year (excluding intrathecal methotrexate)
Serum calcium (corrected for albumin) level at or below the ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment) prior to study therapy initiation
Radiotherapy within one week prior to starting study treatment.
Lesion must be sonographically visible at the time of treatment.
Parts H, and I: Must be able and willing to undergo mandatory tumor biopsies prior to study treatment and at the time of discontinuation from study treatment.
Participants may have either extensive or limited cGVHD requiring systemic treatment
Any previous autologous EBV specific T cell treatment.
Previous treatment for ALL, except for prior steroids and/or hydroxyurea
Previous androgen suppression therapy is allowed if it was completed at least 3 months prior to initiation of study treatment
Patients who have had previous treatment with tivozanib are excluded
Patients who have received investigational or licensed drugs that target vascular endothelial growth factor [VEGF] or VEGF receptors/pathways (such as bevacizumab, sorafenib, pazopanib, sunitinib, axitinib, cabozantinib, etc.) for the treatment of recurrent cancer are not eligible; exceptions: prior treatment with bevacizumab in the up-front or maintenance setting is allowed, provided the patient had a favorable response to bevacizumab; favorable response is defined as having had a disease free interval of > 6 months following completion of a bevacizumab-containing regimen; if questions, contact the principal investigator (PI)
Participants who have received treatment with a TKI within 7 days of the first dose of study treatment; (an alternative appropriate wash-out time based on known duration and time to reversibility of drug related adverse events could be agreed upon by principal investigator and the investigator
Prior treatment with ziv-aflibercept is not allowed
Previous imatinib treatment should be permanently discontinued within 4 days prior randomisation and patient should have recovered from potential toxicity related to imatinib
Patients who have had previous treatment with nintedanib
Evidence of an active lesion including: plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other cancer requiring concurrent treatment with chemotherapy or radiation therapy; patients not requiring treatment for these lesions are eligible for this protocol
Use of hematopoietic growth factors within 4 weeks of treatment
Prior treatment with 89-Strontium or 153-Samarium containing compounds (e.g. Metastron®, Quadramet®)
Prior treatment with cabozantinib
Patient must not have had prior treatment with paclitaxel or nab-paclitaxel
No prior treatment with ONC201.
Participants must not have more than 5 new or progressive lesions in the brain requiring SRS treatment (greater than 5 total brain lesions are allowed as long as no more than 5 lesions require SRS treatment)
Have received treatment with a therapeutic antibody less than 4 weeks before the first dose of AG-270. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of AG-270 may be permitted in subjects with rapidly progressive or aggressive subtypes of lymphoma following discussion with the medical monitor.
Lesion amenable to treatment with both PLA and HIGRT; for PLA treatment this requires the lesion be visible via ultrasound and/or non-contrast CT or feasible per treating physician
Prior treatment with paclitaxel as part of definitive therapy regimen is acceptable, provided the patient is not intolerant of paclitaxel.
Participants with prostate cancer who are unable to interrupt treatment with ketoconazole; ketoconazole treatment must be discontinued 2 weeks prior to first dose of study medication and is not allowed during Cycle 1, but may be used in the optional extension phase.
The disease should be progressing/relapsed during or after the previous treatment.
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
Any investigational agents, anti-cancer monoclonal antibody, anti-cancer therapeutic vaccine, immunostimulant (e.g. IL-2) or study drugs from a previous clinical study within 4 weeks of the first dose of mRNA-4157 or pembrolizumab (note only a 2 week wash out is required from prior pembrolizumab treatment)
Participants must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study
Prior investigational drugs or interventions for invasive breast cancer treatment within 6 months before registration are not allowed; prior participation in window-of-opportunity trials without therapeutic intent is allowed if intervention is no more than 3 weeks in duration
No prior treatment for CAH/EIN/EC
Subject must appropriately be able to complete Screening assessments before beginning treatment for DLBCL, in the judgement of the Investigator. For subjects with bulky disease, B-symptoms, compressive disease, elevated bilirubin due to lymphoma, rapidly progressing adenopathies, or worsening performance status, pre-phase treatment with up to 100 mg/day prednisone, or equivalent, for a maximum of 10 days is permitted prior to beginning the treatment period, at the discretion of the Investigator. A washout period is not required, however, the Screening positron emission tomography (PET), CT, tumor biopsy (if needed), and bone marrow biopsy (if needed) should be completed before initiating corticosteroids.
Prior treatment with any immunotherapy
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Agrees to undergo a pretreatment and a post-treatment biopsy.
Serum calcium (corrected for albumin) level at or below the ULN (treatment of hypercalcemia is allowed and participant may enroll if hypercalcemia returns to normal with standard treatment).
Inclusion Criteria:\n\n        Arms 1 and 2 Participants:\n\n          -  Has any histologically or cytologically confirmed advanced/metastatic solid tumor by\n             pathology report and has received, or have been intolerant to all treatment known to\n             confer clinical benefit. Solid tumors and lymphomas of any type are eligible for\n             enrollment. For cutaneous T-cell lymphoma (CTCL), histopathological diagnosis should\n             be confirmed in a skin biopsy representative of disease.\n\n          -  Have Stage III or Stage IV disease that is not surgically resectable. Stage IIB\n             (T3N0M0B0-1) CTCL participants are eligible.\n\n        Arm 3 Participants:\n\n        -Has metastatic liver and/or liver lesion involvement that does not exceed one third of the\n        total liver volume in participants to be treated by liver IT injection. Hepatocellular\n        carcinoma participants are excluded from eligibility of IT liver injection.\n\n        All Participants:\n\n          -  Stage III or Stage IV disease that is not surgically resectable.\n\n          -  Has ?1 injectable lesion that is amenable to injection and biopsy via visual\n             inspection for a cutaneous lesion, or via ultrasound guidance for a subcutaneous\n             lesion.\n\n          -  Has ?1 discrete, distant noninjected lesion that is amenable to biopsy via visual\n             inspection or amenable to biopsy via image guidance.\n\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.\n\n          -  Demonstrates adequate organ function.\n\n          -  If of childbearing potential, must agree to use adequate contraception during the\n             treatment period and for at least 120 days after the last dose of study treatment.\n\n        Exclusion Criteria:\n\n          -  History of a second malignancy, unless potentially curative treatment has been\n             completed, with no evidence of malignancy for 2 years (except for successful\n             definitive resection of basal cell carcinoma of the skin, superficial bladder cancer,\n             or in situ cervical cancer).\n\n          -  Clinically active central nervous system metastases and/or carcinomatous meningitis.\n\n          -  Severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb).\n\n          -  Active autoimmune disease that has required systemic treatment in the past 2 years.\n\n          -  History of vasculitis.\n\n          -  Active infection requiring therapy.\n\n          -  History of (noninfectious) pneumonitis that required steroids or current pneumonitis.\n\n          -  Undergone prior allogeneic hematopoietic stem cell transplantation within the last 5\n             years.\n\n          -  Known human immunodeficiency virus (HIV) and/or Hepatitis B or C infection.\n\n          -  Pregnant or breastfeeding, or expecting to conceive or father children within the\n             projected duration of the study.\n\n          -  Not fully recovered from any effects of major surgery, and is free of significant\n             detectable infection.\n\n          -  Had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2\n             weeks for palliative radiation) prior to the first dose of study treatment, or has not\n             recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade\n             1 from the AEs due to cancer therapeutics administered >4 weeks earlier.\n\n          -  Been treated within 2 weeks of Cycle 1 Day1 with any of the following: strong/moderate\n             Cytochrome P450 2C9 (CYP2C9) inhibitors, such as: amiodarone, felbamate, fluconazole,\n             miconazole, piperine, oxandrolone, fluorouracil and its derivatives (combination drug\n             tegafur/gimeracil/oteracil [TS-1], Uftoral [UFT], tegafur, carmofur, doxifluridine,\n             capecitabine), sulfaphenazole, cyclosporine, bucurol, tienilic acid; UGT1A3 inhibitors\n             (including ritonavir, quinidine, probenecid, and valproic acid); or strong carbonyl\n             reductase (CBR) inhibitors (including quercetin, menadione, glycyrrhetinic acid, and\n             flufenamic acid).\n\n          -  Currently participating and receiving study therapy or has participated in a study of\n             an investigational agent and has received study therapy or has used an investigational\n             device within 28 days of administration of MK 2118.\n\n          -  Expected to require any other form of antineoplastic therapy while on study.\n\n          -  On chronic systemic steroid therapy in excess of replacement doses (prednisone ?10\n             mg/day is acceptable), or on any other form of immunosuppressive medication. For CTCL,\n             continued use of either prednisone ?10 mg/day or continued use of topical steroids is\n             acceptable.\n\n          -  Received a live vaccine within 28 days prior to first dose.\n\n          -  Been treated with a stimulator of interferon genes (STING) agonist (eg, MK-1454,\n             ADU-S100 [synthetic cyclic dinucleotide (CDN)]).\n\n          -  Has a history of re-irradiation for SCCHN at the projected injection site.\n\n          -  Has a tumor(s) in direct contact or encases a major blood vessel and has ulceration\n             and/or fungation onto the skin surface at the projected injection site.
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment, except prophylactic antibiotics
Any patient receiving treatment with short-acting octreotide, which cannot be interrupted for 48 hours before and 24 hours after the administration of yttrium Y 90-edotreotide (90Y-DOTA-TOC), or any patient receiving treatment with octreotide LAR or lanreotide, which cannot be interrupted for at least 4 weeks before the administration of 90Y-DOTA-TOC\r\n* Concurrent somatostatin receptor analog (SSA) allowed if progression has been documented and the SSA dose has been stable for at least two months; long-acting SSA cannot be given within four weeks of treatment and short-acting SSA cannot be given with 48 hours of treatment; SSA therapy can restart one day after treatment
Participants with symptomatic hyperviscosity or serum IgM > 5,000 mg/dL to undergo plasmapheresis prior to treatment initiation
More than 1 prior VEGF-targeted treatment for advanced RCC
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Patients planning to embark on a new strenuous exercise regimen after the first dose of study treatment
Patients currently receiving active treatment for melanoma
Active hepatitis C (HCV) infection without treatment is permitted; concomitant treatment of HCV is not permitted on this study
Is willing to undergo a mandatory pre-treatment research biopsy
Patients should have been off conventional therapy for at least 1 week prior to receiving treatment on this study
Prior treatment with enzalutamide for CPRC; non-CRPC use is allowed (e.g., neoadjuvant, combined with radiation for localized disease and didn’t progress while on it in those settings)
No prior systemic NSCLC treatment.
Prior treatment with a CD47 or signal regulatory protein (SIRP) alpha targeting agent.
Patients on bisphosphonates may continue receiving bisphosphonate therapy during study treatment
Histologic evidence of DDLS at any time prior to randomization AND current evidence of DDLS requiring treatment
Clinical trials prior to enrollment are allowed, as long as no brain directed therapy was included (current treatment trials are exclusionary)
Confirmation that the patient’s health insurance will pay for the treatment in this study (patients may still be responsible for some costs, such as co-pays and deductibles); if the patient’s insurance will not cover a specific treatment in this study and the patient still wants to participate, confirmation that the patient would be responsible for paying for any treatment received
Treatment with cytarabine at any dose, lenalidomide, or any other therapy targeted to the treatment of MDS (other than growth factors and other supportive care measures) within 4 weeks of planned randomization
Previous treatment with any HER2-targeted therapy Erlotinib
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Prior treatment with cabozantinib (XL184)
Agreement to biopsies before and during treatment, depending on study part
Prior treatment with SGN-LIV1A or prior treatment with an MMAE-containing therapy
Patients receiving immunotherapy for non-cancer related treatment within < 4 weeks of first planned dose of study treatment will be excluded.
Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of napabucasin or while undergoing treatment with nab-paclitaxel and gemcitabine and for 180 days after the last dose of nab-paclitaxel and gemcitabine.
Any number of prior treatment regimens
No prior treatment with enzalutamide, ARN-509, ODM-201, galeterone or other investigational androgen receptor (AR) targeted treatment is allowed
Prior treatment with Provenge vaccine and 223 radium (Xofigo) is allowed if > 4 weeks from last dose
Patients on either treatment arm will considered for crossover if they demonstrate evidence of radiographic disease progression from the initial treatment
Prior treatment with enzalutamide is prohibited
Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of ?100 mg per day, within the last 2 weeks
Prior treatment with abiraterone or other known potent CYP17 inhibitors (e.g., ketoconazole, orteronel) or investigational agents that block androgen synthesis. Previous treatment with itraconazole and fluconazole is permitted.
Prior treatment with enzalutamide or other potent androgen-receptor blockers, approved or experimental (e.g., ARN-509, ODM-201, or galeterone)
Prior treatment with flutamide (Eulexin®), steroidal anti-androgens (e.g., cyproterone acetate, chlormadinone acetate), androgens, or estrogens treatment within 4 weeks of Cycle 1, Day 1
Prior treatment with bicalutamide (Casodex®) or nilutamide (Nilandron®) within 6 weeks of Cycle 1, Day 1
Participants on bisphosphonates may continue receiving bisphosphonate therapy during study treatment
Previous treatment with gemcitabine
Prior treatment with FR-targeting investigational agents is not allowed
Subject is receiving excluded therapy/treatment per protocol
Patient must be accessible for treatment and follow-up.
Presence of at least 1 non-target lesion suitable for multiple biopsies while on treatment.
Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for advanced NSCLC used for a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
Previous hysterectomy and/or prior treatment for cervical precancer condition
Treatment with cytotoxic or targeted antineoplastics within 3 weeks of initiation of study treatment. For cytotoxic agents that have major delayed toxicity a washout period of one cycle is indicated (examples are nitrosoureas and mitomycin C which typically require a 6 week washout). Prior antibodies or immunotherapies require a 6 week washout.
Prior treatment with anti?cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapeutic agents (e.g. ipilimumab)
Subjects must have received at least 1 and not more than 3 previous lines of treatment and have had a response to at least 1 prior Treatment in the past (i.e., achieved a minimal response [MR] or better) according to the IMWG uniform response criteria.
Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical.
Participant has received or will receive some form of treatment for their cancer prior to completing a minimum of 14 days of study agent dosing; (a biopsy is not considered a form of treatment)
TREATMENT INCLUSION: Electrocardiography (EKG) shows no significant arrhythmias
Has demonstrated clinical benefit from treatment with tazemetostat.
Has been permanently discontinued from tazemetostat therapy due to adverse event, intolerance or treatment failure
Participants who have not recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to the study.
Current active treatment in another clinical study.
Patients may have had previous systemic treatment regimens (no limit to number of prior therapies); patients with prior treatment with bevacizumab are eligible for enrollment into the study; NOTE: except for bevacizumab, a 28 day wash-out period prior to registration is mandatory for all systemic treatments
No more than 3 prior lines of treatment for cGVHD.
Use of any vaccines against infectious diseases within 4 weeks of initiation of study treatment.
Prior treatment with at least 2 lines of therapy for HL including brentuximab vedotin; in those patients who cannot receive brentuximab vedotin, treatment with 2 prior therapeutic regimens is sufficient
Note: (supportive transfusions will be allowed during treatment as deemed necessary by the treating physician)
Ongoing treatment with an anticancer agent for CMML not contemplated in this protocol. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 7.
Prior treatment as follows:
Cytoreduction allowed with hydroxyurea and/or leukapheresis for up to 14 days prior to day (D)1 of treatment under LCCC1522; patients must be off hydroxyurea for >= 12 hours prior to D1 of treatment under LCCC1522
For patients that relapse following a response to prior treatment with bortezomib or carfilzomib, six months must have elapsed since the last dose of treatment
Peripheral blood lymphoblasts =< 50,000 mcL; hydroxyurea and/or leukapheresis is permitted to reduce the peripheral blast count prior to enrollment and treatment
Ongoing treatment with Coumadin.
Psoriasis or eczema not requiring systemic treatment.
Consent for on-treatment paired biopsies
Able to tolerate CPI treatment regimen {if already starte
Radiotherapy delivered to non-target lesions within one week prior to starting study treatment or delivered to target lesions that will be followed on the study (note: prior sites of radiation will be recorded).
Willingness to have pre treatment and on treatment tumor biopsies.
Hematologic growth factors are not allowed at Screening or during the first cycle of treatment
Histologically documented cluster of differentiation (CD) 20-positive B-cell lymphoma classified as relapsed or refractory FL or DLBCL after treatment with at least two prior chemoimmunotherapy regimens that included an anti-CD20 monoclonal antibody (mAb) and for which no other more appropriate treatment option exists
Inclusion criteria for all parts of the study\n\n          -  Confirmation of locally advanced/metastatic cancer. Refractory or resistant to\n             standard therapy, or have no effective standard\n\n          -  Aged at least 18 yrs\n\n          -  Reasonable health (performance status 0 or 1), stable over the previous 2 weeks\n\n          -  Females who can have children must use contraception; have a negative pregnancy test,\n             & not be breast feeding\n\n          -  Sexually active male patients must use contraception for duration of study and for 3\n             months afterwards Inclusion criteria for Part B only\n\n          -  Tumour(s) that can be measured by CT or MRI, at least 1cm in size Inclusion Part B\n\n          -  Confirmation of metastatic/locally advanced cancer of specific tumour type which\n             failed to respond to standard treatments Exclusion criteria for all parts of the study\n\n          -  Prior treatment with an ATM inhibitor\n\n          -  Past medical history of an inflammatory type(interstitial) lung disease or current\n             inflammatory lung disease\n\n          -  Radiotherapy within the last 4 weeks, except palliative radiotherapy for bone pain\n             relief\n\n          -  Prior treatment with drugs that may cause lung damage\n\n          -  Poor of lung function\n\n          -  History/presence of muscle weakness or abnormal blood tests relating to muscle\n             function\n\n          -  Cancer affecting the spinal cord and/or brain unless asymptomatic and stable\n\n          -  Any evidence of severe or uncontrolled diseases, active bleeding,kidney transplant, or\n             active infection including liver infections (hepatitis B, hepatitis C) and human\n             immunodeficiency virus (HIV).\n\n          -  Evidence of severe lung infections\n\n          -  Receiving, or having received during the four weeks prior to starting study treatment\n             other chemotherapy treatment for your cancer\n\n          -  Treatment with certain doses of steroids during the two weeks prior to starting study\n             treatment\n\n          -  A known sensitivity to AZD0156 or any of its components\n\n          -  Treatment with any unapproved medicine within 28 days prior to starting study\n             treatment\n\n          -  Receiving, or having received medications, herbal supplements and/or foods that\n             significantly affect how your liver works\n\n          -  Low numbers of certain blood cells\n\n          -  If your liver and kidney aren't working normally\n\n          -  If your heart isn't working normally or you have a strong family history of certain\n             heart diseases\n\n          -  Other cancers within the past 3 years, except for certain types of cervical and skin\n             cancers\n\n          -  Sickness and vomiting, digestive diseases or previous significant bowel removal\n\n          -  Patients with uncontrolled fitting\n\n          -  Infections requiring treatment\n\n          -  Other severe and/or uncontrolled medical conditions in addition to your cancer\n\n          -  A blockage in your digestive system or severe bleeding from the stomach within 4 weeks\n             before your take medication on the stuy\n\n          -  Patients with acute leukaemia or certain bone marrow diseases\n\n          -  Patients with a known sensitivity to olaparib or its components (Module 1), or\n             components of FOLFIRI (Module 2)\n\n          -  Any previous treatment with drugs that work like olaparib. (Module 1 Only)
Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo BMT
Treatment with colchicine is excluded.
Prior treatment with lenalidomide; patients previously treated with thalidomide who discontinued treatment for reasons aside from an adverse reaction to thalidomide are permitted
Prior treatment with a monoclonal antibody or chimeric antigen receptor T cell infusion for the treatment of AML
Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Prior treatment with afatinib
Subjects are willing to undergo a biopsy to confirm lower GI aGVHD. Biopsy results are not needed to initiate treatment. However, if aGVHD is not confirmed histologically, treatment with F-652 will be discontinued.
Subjects, who have received previous systemic corticosteroids treatment or poorly absorbable corticosteroids for the treatment of aGVHD, for longer than 3 days (72 hours).
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Patients undergoing primary medical treatment (hormone or chemotherapy) as initial treatment with neoadjuvant intent of reducing tumor size
relevant toxicity from previous treatment
Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.
Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment and would interfere with follow-up assessments through year 5
Must have fully recovered from toxicities of any prior treatment with cytotoxic drugs, radiotherapy, surgery, or other anti-cancer modalities (returned to baseline status as noted before most recent treatment or =< grade 1)
All previous cancer therapy (with the exception of hydroxyurea) including donor lymphocyte infusions must have been discontinued at least 2 weeks prior to treatment in this study
Prior treatment with any anti-angiogenic agent (including bevacizumab)
Unresolved toxicity from prior radiation, chemotherapy, or other targeted treatment, including investigational treatment
Patients may have received treatment of completely resected early stage melanoma, comprising interferon, radiation treatment, or experimental vaccine therapy, and in the metastatic setting patient can have had treatment such as chemotherapy, immunotherapy (except prior treatment with ipilimumab and IL-2), and other experimental agent which was completed 4 weeks prior to enrollment
Patients may be treatment-naive or have failed previous regimen of intravesical therapy
At least 3 weeks beyond the last chemotherapy, targeted anticancer agent, major surgery or experimental treatment and recovered from all acute toxicities (? Grade 1). Hydroxyurea used to control peripheral blast counts is permitted up to Day 7 of treatment on study.
Have been informed of other treatment options
Prior treatment with compounds with the same mode of action
Prior treatment with bevacizumab or other agents targeting vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR)
Patient’s physician has already recommended enzalutamide for treatment of progression
Previous treatment with enzalutamide (MDV3100)
No systemic treatment in the previous 28 days.
Have taken any chemotherapeutic agent within 5 weeks of treatment with the NanoKnife irreversible electroporation (IRE) system
Lenalidomide-related toxicities before ASCT necessitating its discontinuation as part of treatment
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Patients who have had previous treatment with bevacizumab and/ or NovoTTF 100A system
Concomitant treatment with other anti-neoplastic agents, with the exception, when clinically indicated, of prophylaxis in the post-transplantation setting with intrathecal chemotherapy
History of changes in baseline LVEF that occurred during prior treatment with anti-HER2 treatment
For Cohorts 1, 3 and 4 only: Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL. Cohort 8: Received prior treatment with bendamustine and did not respond during treatment or relapsed less than sex months after completing treatment.
Concurrent systemic treatment or prior therapy within 4 weeks for SMM; NOTE: Treatment with corticosteroids for other indications is permitted
Patients who have not fully recovered from toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). The required minimum time elapsed from prior treatments are:
treatment with molecular targeted agents within 2 weeks prior to treatment with APS001F.
Patients with previous treatment with abraxane
Patients should be > 24 hours from radiation therapy (RT) treatment to areas of the neuro-axis and all effects of treatment should have resolved
TREATMENT WITH SJCAR19: Known primary immunodeficiency
Hematologic growth factors are not allowed at screening or during the first cycle of treatment
Prior treatment with folate receptor (FR) targeting investigational agents is allowed for dose escalation provided that such treatment was not discontinued due to adverse events; prior FR-targeting investigational agents are not allowed for patients in the expansion cohort
Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
Diagnosis and Prior Treatment:
Prior history of treatment with blinatumomab
Prior treatment with a therapeutic agent targeting CD33 and/or CD3 (e.g. gemtuzumab ozogamicin, SGN-CD33A or AMG 330).
Treatment with systemic immunostimulatory agents;
Major surgery within prior 4 weeks of treatment initiation (the surgical incision should be fully healed prior to all neoadjuvant treatment initiation)
Prior enzalutamide and/or abiraterone treatment is allowed
Any prior PSA, MUC1, and/or brachyury-targeted immunotherapy (e.g., vaccine) must have been discontinued at least 12 weeks before initiation of study treatment; subjects must have recovered from all acute toxicities from prior treatment prior to screening for this study
Prior treatment with adenovirus-based vectors immunotherapy
No prior treatment with temozolomide
Subject must have received no prior treatment for AML; hydroxyurea is not considered a treatment and is allowed
Prior treatment with ixazomib
Treatment failure of either abiraterone and/or enzalutamide as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL) while receiving treatment with either abiraterone and/or enzalutamide
Previous first line treatment with at least radiotherapy.
An interval of >= 4 weeks after the last administration of any other treatment for GBM.
WOCBP must use appropriate method(s) of contraception from the time of enrollment for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 30 days (duration of ovulatory cycle) for a total of 23 weeks post treatment completion for subjects enrolled to treatment arm A (nivolumab). Subjects enrolled to treatment arm B (nivolumab + bevacizumab) must use appropriate method(s) of contraception for 6 months post treatment completion.
Previous treatment with carmustine wafer except when administered as first line treatment and at least 6 months prior to randomization.
Previous bevacizumab or other vascular endothelial growth factor (VEGF) or anti-angiogenic treatment.
Prior treatment with ADI-PEG 20, gemcitabine, or docetaxel
Dose Expansion cohorts: Prior treatment with osimertinib (Tagrisso®). Prior treatment with osimertinib (Tagrisso®) is allowed for subjects participating in the dose escalation portion of the study
Cohort #1: received only frontline CD20-directed immunotherapy with anthracycline- or anthracenedione-based multi-agent chemotherapy for patients with DLBCL; monotherapy rituximab or other CD20-directed immunotherapy prior to frontline chemotherapy, as maintenance therapy, and radiotherapy in a limited field or as a part of the frontline treatment plan are permitted; last treatment dose should be 3 weeks before start of study treatment
Prior systemic treatment of any kind or radiotherapy for RCC
Requires prohibited treatment (i.e., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor). Limited field single dose radiotherapy for pain palliation would be allowed.
Cohort A: Patients must have progressed during treatment with abiraterone
Patients who are currently receiving treatment with contraindicated corrected QT interval (QTc) prolonging medications or potent CYP3A4 inducers, if that treatment cannot be either discontinued or switched to a different medication prior to first day of study treatment
Treatment with prohibited medications (concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterolacetate], or immunotherapy) =< 14 days prior to treatment with osimertinib
Patients must have had at least prior treatment with a fluoropyrimidine and either oxaliplatin or irinotecan.
Had prior treatment with Gliadel
Ability to comply with treatment, PK and test schedules
Prior treatment with CD74 targeting therapy
A medically appropriate candidate for ibrutinib treatment (based on the judgement of the clinical investigator).
Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs) (see Appendix B), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent dexamethasone is allowed.
Treatment with any of the drugs listed in Section 8.4.5 at the time of study treatment initiation.
Concurrent opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system; patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
Has an adequate treatment washout period prior to enrollment
Any prior treatment with azacitidine or decitabine
Have a documented advanced (metastatic and/or unresectable) gastroesophageal adenocarcinoma that is incurable and for which prior first-line or later-line standard of care (SOC) treatments have failed. There is no limit to the number of prior treatment regimens. Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.
Patients excluded with any prior treatment of pneumonitis requiring corticosteroids.
Subjects may have previously progressed on treatment with one of the 3 agents being used in this trial or treatment with other checkpoint inhibitors, as long as they have recovered from previous toxicity; subjects that previously progressed on treatment with a combination of any 2 of the 3 agents being used in this trial are eligible for the triplet cohort only
Must be agreeable to the mandatory research tumor biopsies (pre-treatment and on-treatment); tumor biopsies are mandatory at pre-treatment and at on-treatment; there is an optional biopsy at post-progression
Prior treatment with blinatumomab or CD-directed CAR T-cell therapy
Immunotherapy-naive and have either progressed on, are intolerant to, or refused treatment with sorafenib. Subjects who receive treatment with systemic therapies other than sorafenib are not eligible.
In stratum A, patients must have failed one prior systemic chemotherapy regimen; in stratum B, patients must have failed one prior systemic chemotherapy regimen, which must include cladribine/cytarabine or are not considered to be eligible for such treatment; in stratum C, Rosai Dorfman disease (RDD) patients must have failed treatment with corticosteroid; Erdheim Chester disease (ECD) patients who have confirmed BRAF V600E mutation must have failed treatment with a BRAF inhibitor or are not considered to be eligible for such treatment
Need for systemic treatment with corticosteroids for cGVHD
No previous systemic treatment for cGVHD (including extracorporeal photopheresis [ECP])
Participants may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d
Prior treatment with NKTR-102.
Previous treatment with a pyrrolobenzodiazepine (PBD)-based drug Additional exclusion criteria for the SC-003 and ABBV-181 combination treatment regimen:
Extensive concurrent perianal or lower vulvar HSIL or condyloma requiring a different treatment modality than the study treatment, or treatment that cannot be deferred in observation arm, per examining provider
Treatment for anal or perianal HSIL, low-grade squamous intraepithelial lesion (LSIL) or condyloma within 4 months of randomization; please note that infrared coagulation (IRC) or electrocautery of a biopsy site to stop bleeding does not constitute treatment
Radiotherapy (except for brain and extremities or stereotactic treatment) within the past 2 weeks prior to treatment with the trial drug
Prior treatment with nintedanib (BIBF1120)
Prior Treatment\r\n* Patient must have failed at least one prior systemic therapy that included everolimus; disease progression or treatment intolerance leading to discontinuation is considered treatment failure\r\n* Prior treatment (except somatostatin analogs) with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, and/or radiation must be completed at least 28 days prior to registration\r\n* Prior treatment with somatostatin analogs is allowed, and continuation of treatment with somatostatin analogs while on cabozantinib/placebo is allowed provided that the patient has been on a stable dose for at least two months\r\n* Prior systemic treatment with radionuclide therapy must be completed at least 6 weeks prior to registration\r\n* Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective internal radiation therapy) or ablative therapies is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site; prior liver-directed or other ablative treatment must be completed at least 28 days prior to registration\r\n* Prior treatment with cabozantinib is not allowed\r\n* Patients should have resolution of any toxic effects of prior therapy (except alopecia and fatigue) to National Cancer Institute (NCI) CTCAE, version 5.0, grade 1 or less\r\n* Patients must have completed any major surgery at least 12 weeks prior to registration and any minor surgery (including uncomplicated tooth extractions) at least 28 days prior to registration; complete wound healing from major surgery must have occurred at least 28 days prior to registration, and complete wound healing from minor surgery must have occurred at least 10 days prior to registration
No prior treatment with an anthracycline and taxane
Other clinically significant disorders such as: i. active infection requiring systemic antibiotic treatment within 14 days before the first dose of study treatment ii. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment iii. history of organ transplant iv. concurrent uncompensated hypothyroidism or thyroid dysfunction (thyroid-stimulating hormone [TSH] above 10) within 28 days before the first dose of study treatment v. major surgery within 12 weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment. Minor surgery within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
Any prior treatment for NSCLC
Relapsed or refractory after at least one prior treatment regimen
No prior treatment with a hypomethylating agent, or previous exposure to DEC-205/NY-ESO-1 fusion protein CDX-1401 (CDX-1401)
Actively participating in another clinical treatment trial
Any prior treatment for SCCHN
Patient has been previously permanently discontinued from study treatment in the parent protocol.
A WOCBP who agrees to follow the contraceptive guidance in protocol during the treatment period and for at least 120 days after the last dose of trial treatment.
Presence of at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by irRECIST
Participants may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days prior to registration; participants should also be adequately recovered from acute toxicities of prior treatment
Participants on bisphosphonates may continue receiving bisphosphonate therapy during study treatment
Unwillingness to accept the treatment;
Concomitant therapy that includes other chemotherapy that is or may be active against AML except for prophylaxis and/or treatment of opportunistic or other infection with antibiotics, antifungals and/or antiviral agents.
Resolution of treatment-related toxicities.
Inclusion Criteria:\n\n        For inclusion in this study, patients must fulfil the following criteria:\n\n          -  Has read and understands the informed consent form (ICF) and has given written\n             informed consent prior to any study procedures.\n\n          -  Female or male aged ?18 years.\n\n          -  Has completed 1 of the parent AZD1775 clinical pharmacology studies (ie, D6014C00002,\n             D6014C00003, D6014C00004, D6014C00005, or D6014C00006) and in the Investigator's\n             opinion will continue to benefit from treatment with AZD1775. Patients who discontinue\n             early from the parent study will be considered by the Sponsor and treating physician\n             on a case-by-case basis.\n\n          -  Any prior radiation must have been completed at least 7 days prior to the start of\n             study treatment, and patients must have recovered from any acute effects prior to the\n             start of study treatment.\n\n          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.\n\n          -  Baseline laboratory values within 7 days of study treatment initiation in the CA\n             study:\n\n               -  Absolute neutrophil count (ANC) ?1500/?L.\n\n               -  Haemoglobin ?9 g/dL.\n\n               -  Platelets ?100,000/?L.\n\n               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ?3 x upper\n                  limit of normal (ULN) or ?5 x ULN if known hepatic metastases.\n\n               -  Serum bilirubin within normal limits or ?1.5 x ULN in patients with liver\n                  metastases; or total bilirubin ?3.0 x ULN with direct bilirubin within normal\n                  limits in patients with well documented Gilbert's Syndrome.\n\n               -  Serum creatinine ?1.5 x ULN, or measured creatinine clearance (CrCl) calculated\n                  by Cockcroft-Gault method ?45 mL/min (confirmation of creatinine clearance is\n                  only required when creatinine is >1.5 x ULN) CrCl (glomerular filtration rate) =\n                  (140-age) x (weight/kg) x Fa (72 x serum creatinine mg/dL) where F = 0.85 for\n                  females and F = 1 for males.\n\n          -  Female patients who are of non-childbearing potential and fertile women of\n             childbearing potential (WoCBP) who agree to use adequate contraceptive measures that\n             are in place during screening (or consent), for the duration of the study, and for 1\n             month after treatment stops; who are not breastfeeding; and who have a negative serum\n             or urine pregnancy test prior to the start of study treatment.\n\n          -  Male patients must be willing to use barrier contraception (ie, condoms) for the\n             duration of the study and for 3 months after study treatment discontinuation.\n\n          -  Willingness and ability to comply with the study and the follow-up procedures.\n\n        Exclusion Criteria:\n\n        Patients must not enrol in this study if any of the following exclusion criteria are\n        fulfilled:\n\n          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca\n             personnel and/or personnel at the study centre).\n\n          -  Previous enrolment and received study treatment in the present study. Patients can,\n             however, be re-screened if the reason for the screen failure no longer exists.\n\n          -  Concurrent enrolment in another clinical study, unless it is an observational\n             (non-interventional) clinical study or the follow-up period of an interventional\n             study.\n\n          -  Must not have received another systemic anti-cancer therapy in the interval following\n             participation in the AZD1775 clinical pharmacology study and the start of treatment on\n             the CA protocol.\n\n          -  Not developed any clinical findings suggestive of brain metastasis. Patients continue\n             to be neurological stable and remain off systemic corticosteroids following treatment\n             of known brain metastases.\n\n          -  Did not tolerate AZD1775 in the parent study in the opinion of the Investigator.\n\n          -  Where a course of palliative radiotherapy was indicated, the last fraction must have\n             been delivered before the start of study treatment on the CA study.\n\n          -  Major surgical procedures ?28 days of beginning study treatment, or minor surgical\n             procedures ?7 days. No waiting period required following port-a-cath placement or\n             other central venous access placement.\n\n          -  Grade >1 toxicities from prior therapy, according to the Common Terminology Criteria\n             for Adverse Events (CTCAE), excluding alopecia or anorexia.\n\n          -  Continue to be able to swallow oral medication, did not undergo placement of a\n             percutaneous endoscopic gastrostomy tube and did not require total parenteral\n             nutrition.\n\n          -  Has had prescription or non-prescription drugs or other products known to be sensitive\n             to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be\n             moderate to strong inhibitors/inducers of CYP3A4 between the parent study and entry\n             into this CA study. Co administration of aprepitant or fosaprepitant during this study\n             is prohibited.\n\n          -  Has consumed herbal preparations between the parent study and entry into this CA\n             study.\n\n          -  Has consumed grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,\n             or other products containing grapefruit or Seville oranges between the parent study\n             and entry into the CA study.\n\n          -  Any known hypersensitivity or contraindication to AZD1775 or to the components\n             thereof.\n\n          -  Any of the following cardiac diseases currently or within the last 6 months as defined\n             by the New York Heart Association ?Class 2:\n\n               -  Unstable angina pectoris.\n\n               -  Congestive heart failure.\n\n               -  Acute myocardial infarction.\n\n               -  Conduction abnormality not controlled with pacemaker or medication.\n\n               -  Significant ventricular or supraventricular arrhythmias (patients with chronic\n                  rate-controlled atrial fibrillation in the absence of other cardiac abnormalities\n                  are eligible).\n\n          -  AZD1775 should not be given to patients who have a history of Torsades de pointes\n             unless all risk factors that contributed to Torsades have been corrected. AZD1775 has\n             not been studied in patients with ventricular arrhythmias or recent myocardial\n             infarction.\n\n          -  Patient with mean resting QTc interval (specifically QTc calculated using the\n             Fridericia formula [QTcF]) >450 ms for males and >470 ms for females from 3\n             electrocardiograms (ECGs) performed within 2 to 5 minutes apart during screening, or\n             congenital long QT syndrome.\n\n          -  Pregnant or lactating female patients.\n\n          -  Serious, symptomatic active infection at the time of study entry, or another serious\n             underlying medical condition that would impair the ability of the patient to receive\n             study treatment.\n\n          -  Active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
Inclusion Criteria:\n\n          -  Patient has histologically or cytologically proven advanced (unresectable) or\n             metastatic cancer as outlined below according to study part and disease type:\n\n          -  Part A: Patients with previously treated advanced or metastatic cancer. Patient may\n             have received no more than 4 lines of treatment for advanced or metastatic cancer.\n             Hormonal treatment will not be considered a prior line of treatment.\n\n          -  Part B: Patients with advanced or metastatic cancer for which treatment with\n             carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no\n             more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment\n             will not be considered a prior line of treatment.\n\n          -  Part C: Patients with previously treated advanced or metastatic cancer. Patient may\n             have received no more than 4 lines of treatment for advanced or metastatic cancer.\n             Hormonal treatment will not be considered a prior line of treatment.\n\n          -  Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered\n             appropriate therapy. Patient may have received no more than 1 prior line of\n             chemotherapy in the metastatic setting. Hormonal treatment will not be considered a\n             prior line of treatment.\n\n          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n\n          -  Patient has adequate organ function\n\n          -  Female patient has a negative serum pregnancy test within 72 hours prior to taking\n             study treatment if of childbearing potential and agrees to abstain from activities\n             that could result in pregnancy from screening through 180 days after the last dose of\n             study treatment, or is of non-childbearing potential.\n\n          -  Male patient agrees to use an adequate method of contraception and not donate sperm\n             starting with the first dose of study treatment through 90 days after the last dose of\n             study treatment. Note: Abstinence is acceptable if this is the established and\n             preferred contraception for the patient.\n\n          -  Patient has measurable lesions by RECIST v1.1.\n\n        For Part A and C, in addition to the general inclusion criteria, patients must also meet\n        the following additional criterion to be considered eligible to participate in this study:\n\n          -  Patient is able to take oral medications.\n\n          -  For patients to be eligible for any parts of the study using niraparib 300 mg as a\n             starting dose, a screening actual body weight ? 77 kg and screening platelet count ?\n             150,000 u/L is necessary.\n\n        Exclusion Criteria:\n\n        (Patients will not be eligible for the study entry if any of the following criteria are\n        met)\n\n          -  Patient has known active central nervous system metastases, carcinomatous meningitis,\n             or both.\n\n          -  Patient has a known additional malignancy that progressed or required active treatment\n             within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous\n             cell carcinoma of the skin that has undergone potentially curative therapy, or in situ\n             cervical cancer.\n\n          -  Patient is considered a poor medical risk due to a serious, uncontrolled medical\n             disorder, nonmalignant systemic disease, or active infection that requires systemic\n             therapy.\n\n          -  Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia),\n             therapy, or laboratory abnormality that might confound the study results or interfere\n             with the patient's participation\n\n          -  Patient is pregnant or expecting to conceive children within the projected duration of\n             the study, starting with the screening visit through 180 days after the last dose of\n             study treatment.\n\n        Note: No data are available regarding the presence of niraparib or its metabolites in human\n        milk, or on its effects on the breastfed infant or milk production. Because of the\n        potential for serious adverse reactions in breastfed infants from niraparib, female\n        patients should not breastfeed during treatment with niraparib and for 1 month after\n        receiving the final dose.\n\n          -  Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).\n\n          -  Patient has known active hepatitis B or hepatitis C.\n\n          -  Patient has an active autoimmune disease that has required systemic treatment in the\n             past 2 years.\n\n          -  Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2,\n             anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically\n             targeting T-cell co-stimulation or checkpoint pathways.\n\n          -  Patient has undergone prior treatment with a known PARP inhibitor.\n\n          -  Known history or current diagnosis of MDS or AML.\n\n        For Parts C and D only, patients will not be eligible for study entry if the following\n        additional exclusion criterion is met:\n\n          -  Patient has clinically significant cardiovascular disease (e.g., significant cardiac\n             conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac\n             arrhythmia or unstable angina, New York Heart Association Grade 2 or greater\n             congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or\n             greater peripheral vascular disease, and history of cerebrovascular accident [CVA])\n             within 6 months of enrollment.\n\n          -  Patient has a history of bowel obstruction, including subocclusive disease, related to\n             the underlying disease and history of abdominal fistula, gastrointestinal perforation,\n             or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic\n             examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.\n\n          -  Patient has proteinuria as demonstrated by urine protein: creatinine ratio ?1.0 at\n             screening or urine dipstick for proteinuria ?2 (patients discovered to have ?2\n             proteinuria on dipstick at baseline should undergo 24-hour urine collection and must\n             demonstrate <2 g of protein in 24 hours to be eligible).\n\n          -  Patient is at increased bleeding risk due to concurrent conditions (e.g., major\n             injuries or surgery within the past 28 days prior to start of study treatment, history\n             of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or\n             clinically significant hemorrhage within the past 3 months).\n\n          -  Patient has a known hypersensitivity to bevacizumab components or excipients
Prior treatment with TAS-102
Concomitant use of potent CYP3A4/5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment
Prior treatment with cisplatin and/or gemcitabine
Active gout or inflammatory arthritis requiring treatment
Inclusion Criteria:-\n\n          -  Participants with histologically confirmed advanced ovarian cancer or triple negative\n             breast cancer who in the opinion of the Investigator are appropriate for this study\n\n          -  Measurable disease by RECIST criteria version 1.1 prior to study drug administration\n\n          -  Performance status of 0 or 1 on the eastern Cooperative Oncology Group (ECOG) scale\n\n          -  Life expectancy, in the opinion of the Investigator, of at least 3 months\n\n          -  Disease-free of active second/secondary or prior malignancies for => 2 years with the\n             exception of squamous cell carcinoma of the skin, or carcinoma in situ of the cervix\n             or breast\n\n          -  Willing to provide the protocol specified tumor biopsies\n\n          -  Acceptable hematologic status, liver and renal function\n\n          -  Participants who have received prior treatment with CD137 agonists or immune\n             checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1\n             therapeutic antibodies, may be enrolled, provided the following requirements are met:\n\n               -  Minimum of 5 months from the last dose of anti-PD-1, anti-CTLA-4, anti-PD- L1 or\n                  CD137 agonist treatment\n\n               -  No history of severe immune-related adverse effects from CD137 agonist,\n                  anti?CTLA-4, anti-PD-1 or anti-PD-L1 (NCI CTCAE Grade 3 and 4). Any toxicity\n                  related to the therapy must have resolved completely, no residual toxicity as\n                  assessed by NCI CTCAE (v4.03)\n\n          -  Agree to use protocol defined methods of contraception\n\n        Exclusion Criteria:\n\n          -  Participants with history of prior malignancy except solid tumor treated curatively\n             more than 3 years ago without evidence of recurrence\n\n          -  Asymptomatic or symptomatic, untreated, or actively progressing central nervous system\n             (CNS) metastases\n\n          -  History of leptomeningeal disease\n\n          -  Uncontrolled tumor-related pain\n\n          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent\n             drainage procedures. Participants with indwelling catheters are allowed.\n\n          -  Uncontrolled or symptomatic hypercalcemia\n\n          -  New York Heart Association Class III or IV cardiac disease, pericarditis, myocardial\n             infarction within the past 6 months, unstable arrhythmia\n\n          -  Fredericia-corrected QT interval (QTcF) > 470 milli seconds (msec) (female) or > 450\n             msec (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG)\n             abnormality, including pericarditis, which in the opinion of the Investigator would\n             preclude safe participation in the study.\n\n          -  Active, uncontrolled bacterial, viral, or fungal infections within 7 days of study\n             entry requiring systemic therapy\n\n          -  Known clinically important respiratory impairment\n\n          -  History of major organ transplant\n\n          -  History of an autologous or allogeneic bone marrow transplant\n\n          -  Serious non-malignant disease that could compromise protocol objectives in the opinion\n             of the Investigator and/or the Sponsor\n\n          -  Pregnant or nursing women\n\n          -  Any systemic anticancer therapy within 3 weeks prior to Cycle 1 Day 1\n\n          -  Any radiation treatment to metastatic site within <= 14 days of Cycle 1 Day 1\n\n          -  Major surgical procedure, open biopsy, or significant traumatic injury within 30 days\n             prior to Cycle 1 Day 1 or anticipation of need for major surgical procedure during the\n             course of the study\n\n          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to\n             chimeric or humanized antibodies or fusion proteins\n\n          -  Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster\n             ovary cells or any component of the atezolizumab formulation\n\n          -  Active or history of autoimmune disease\n\n          -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced\n             pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic\n             organizing pneumonia), or evidence of active pneumonitis on screening chest computed\n             tomography (CT) scan. History of radiation pneumonitis in the radiation field\n             (fibrosis) is permitted\n\n          -  Positive test for Human immunodeficiency virus (HIV)\n\n          -  Active hepatitis B or hepatitis C\n\n          -  Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or\n             anticipation that such a live, attenuated vaccine will be required during the study\n\n          -  Treatment with investigational therapy within 28 days prior to initiation of study\n             treatment\n\n          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation\n             of study treatment\n\n          -  Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the\n             first dose of study treatment and during the study\n\n          -  Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the\n             first dose of study treatment and during the study\n\n          -  Treatment with systemic immuno-stimulatory agents within 4 weeks or five half-lives of\n             the drug (whichever is shorter) prior to the first dose of study treatment\n\n          -  Treatment with systemic corticosteroids or other systemic immunosuppressive\n             medications within 2 weeks prior to the first dose of study treatment, or, anticipated\n             requirement for systemic immunosuppressive medications during the trial\n\n          -  History of allergic reactions attributed to components of the formulated product(s)\n\n          -  Unwillingness or inability to comply with procedures required in this protocol
Within 10 days of treatment initiation: Hematological\r\n* It is anticipated that refractory AML patients will have low hematological counts including platelet count, hemoglobin, and absolute neutrophil count. Thus, hematologic parameters will not be used for enrollment and initiation of treatment
Bisphosphonate treatment within 7 days prior to initiating study treatment (while on study, bisphosphonates can be administered only once a month, between Days 18 to 21 of the 28-day treatment cycle)
Must have an absolute blast count (ABC) of < 15 K/ul in the peripheral blood prior to initiating study treatment, performed within 10 days of treatment initiation; use of hydroxyurea to control blast counts prior to initiating study treatment is acceptable
Previous treatment with CD19-targeted CAR T cells
At least one cutaneous lesion that is amenable to treatment with topical imiquimod
Has previous treatment for higher-risk myelodysplastic syndromes (HR MDS) or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.
Treatment with prohibited medications (including concurrent anticancer therapy including chemotherapy, radiation, hormonal treatment [except corticosteroids and megestrol acetate]) =< 14 days prior to treatment
Prior treatment as follows:
In dose expansion, patients must be willing to undergo a pre-treatment biopsy, and four research PET imaging techniques (11C-Glutamine and 18F-FSPG), two pre-treatment and two after one cycle of treatment
Patients receiving anti-herpes medication (i.e., acyclovir, famciclovir, or valacyclovir) within 1 week prior to initiating HF10 treatment; patients may not require intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug other than intermittent topical use
The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry
Subjects can be treatment naive or may have had two prior regimens for recurrent cancer. They must be naive to treatment with PD-1/L1 or CTLA-4 inhibitors.
Any prior treatment with pomalidomide. Subjects who have prior treatment with other immunomodulatory compounds (thalidomide, lenalidomide) ARE eligible if they meet all other eligibility criteria and did not have allergic reactions or other \significant toxicity\ per Investigator discretion associated with lenalidomide or thalidomide use.
Subjects unable or unwilling to have their first randomized treatment within three weeks of the post induction imaging and within five weeks of their last induction treatment
Known active infection requiring parenteral anti-infective treatment at the time of initiation of treatment
Inclusion Criteria:\n\n          1. Fully understand the study and voluntarily sign the informed consent form;\n\n          2. 18-75 years of age\n\n          3. Body weight ? 45kg\n\n          4. Histologically or cytologically documented, locally advanced or metastatic solid\n             malignancy (except squamous NSCLC) that has progressed on approved systemic therapy,\n             the last dose of prior systemic anti-cancer therapy must have been administered ? 4\n             weeks prior to initiation of study treatment, and for whom no effective therapy or\n             standard of care exists.\n\n          5. Have measurable disease per RECIST Version 1.1 (expansion phase only)\n\n          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n\n          7. Expected survival of more than 12 weeks;\n\n          8. For female patients of childbearing potential and male patients with partners of\n             childbearing potential, agreement (by patient and partner) to use a highly effective\n             form(s) of contraception that results in a low failure rate ( < 1% per year) when used\n             consistently and correctly, and to continue its use for 90 days after the last dose of\n             fruquintinib.\n\n        Exclusion Criteria:\n\n        Patients will be excluded from the study, if any of the following criteria is met:\n\n          1. Absolute neutrophil count (ANC) < 1.5×109/L, platelet count < 100 ×109/L, or\n             hemoglobin < 90 g/L;\n\n          2. Serum total bilirubin > 1.5 times the upper limit of normal (ULN);\n\n          3. Alanine aminotransferase (ALT) aspartate aminotransferase (AST) > 1.5 ULN in patients\n             without hepatic metastases or ALT, AST > 3 ULN in patients with hepatic metastases;\n\n          4. Serum potassium, calcium, or magnesium levels out of the normal laboratory reference\n             range, and clinically significant in the investigator's judgment.\n\n          5. Serum creatinine clearance < 60 mL/min;\n\n          6. Urine dipstick for proteinuria > 2 +. Patients discovered to have ? 1 + proteinuria on\n             dipstick urinalysis at baseline should undergo a 24-hour urine collection and must\n             demonstrate ? 1 g of protein in 24 hours;\n\n          7. Uncontrolled hypertension, defined as: systolic blood pressure ? 140 mmHg and/or\n             diastolic blood pressure ? 90mmHg;\n\n          8. International Normalized Ratio (INR) > 2 or activated partial thromboplastin time\n             (aPTT) > 1.5 ULN, except if the patient is currently receiving or intending to receive\n             anti-coagulants for therapeutic purposes (prophylactic use is allowed).\n\n          9. Risk of, or active hemorrhage: history or presence of active gastric/duodenal ulcer or\n             ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, or any\n             other condition that could possibly result in gastrointestinal tract hemorrhage or\n             perforation;\n\n         10. History or presence of hemorrhage from any other site (e.g., hemoptysis or\n             hematemesis) within 2 months prior to screening\n\n         11. History of a thromboembolic event (including DVT, pulmonary embolism, stroke and/or\n             transient ischemic attack) within 12 months prior to screening;\n\n         12. Patients with squamous non-small-cell lung cancer (NSCLC);\n\n         13. Clinically significant cardiovascular disease, including but not limited to acute\n             myocardial infarction or coronary artery bypass surgery within 6 months prior to\n             enrollment, severe or unstable angina pectoris, New York Heart Association Class\n             III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left\n             ventricular ejection fraction (LVEF) < 50%;\n\n         14. Mean corrected QT interval using the Fredericia method (QTcF) > 480 msec or any\n             factors that increase the risk of QTc prolongation or risk of arrhythmic events such\n             as hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or\n             unexplained sudden death under 40 years of age in a next of kin relative.\n\n         15. Concomitant medications with a known risk of causing QT prolongation and/or Torsades\n             de Pointes (See list in Appendix E; source list is continuously updated online at\n             www.qtdrugs.org ).\n\n         16. Systemic anti-neoplastic therapies within 4 weeks prior to the initiation of\n             investigational treatment, including chemotherapy, radical radiotherapy,\n             hormonotherapy, bio-therapy and immunotherapy;\n\n         17. Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the\n             initiation of study treatment;\n\n         18. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of\n             study treatment (3 weeks for St John's Wort). See Appendix F for a list of such\n             medications.\n\n         19. Surgery prior to enrollment within 28 days prior to the initiation of study treatment\n             or unhealed surgical incision;\n\n         20. Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1\n             (except for alopecia);\n\n         21. Known human immunodeficiency virus (HIV), hepatitis A, B or C infection except for\n             fully recovered Hepatitis A. Previous medical history of hepatitis B virus (HBV)\n             infection regardless of drug control, HBV DNA ?104 ×copy number or ?2000 IU/mL;\n\n         22. Known clinically significant history of liver disease, including hepatitis or\n             cirrhosis; current alcohol abuse.,\n\n         23. Evidence of ongoing or active infection requiring intravenous antibiotics;\n\n         24. Women who are pregnant or lactating;\n\n         25. Central nervous system (CNS) metastatic disease or prior cerebral metastasis;\n\n         26. Inability to take medication orally, dysphagia or an active gastric ulcer resulting\n             from previous surgery (e.g., gastric bypass) or a severe gastrointestinal disease, or\n             any other condition that investigators believe may affect absorption of the\n             investigational product;\n\n         27. Received investigational treatment in another clinical study within 4 weeks prior to\n             the initiation of investigational treatment;\n\n         28. Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory\n             result, or any other condition that investigators suspect may prohibit use of the\n             investigational product, affect interpretation of study results, or put the patient at\n             undue risk of harm.
Any number of prior treatments allowed for patients under 65 years (y), over 65y must have at least one prior line of TKI treatment (excluding anaplastic patients).
No prior virotherapy allowed
Documented disease progression or intolerance to treatment either during or after treatment with most recent therapy
A new diagnosis of de novo, secondary or treatment-related AML
Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication (not known to affect QT interval) prior to cycle 1 day 1 (C1D1)
Patients must consent to pre and on treatment research biopsies
Presence of at least one target lesion (distinct from treatment lesion and outside of treatment lesion radiation field) evaluable for response by RECIST 1.1
Subjects with prior anti-PD-1, anti-PD-L1 treatment. For Arms A and D, subjects may not have had prior 4-1BB treatment. For Arms B and E, subjects may not have had prior OX40 treatment. For Arms C and F, subjects may not have had prior 4-1BB or OX40 treatment.
Prior treatment with cabozantinib or erlotinib
Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment
Willing to have peripheral blood mononuclear cells and bone marrow biopsies to be collected prior to receiving the first dose of durvalumab and tremelimumab, after 2-doses and 4-doses of durvalumab and tremelimumab, after 2nd treatment administration and 4th treatment administration.
Previous treatment with investigational gene or chimeric antigen receptor therapy;
Prior yttrium-90 radioembolization treatment
Patient willingness and disease accessible to pre-treatment, on-treatment tumor, and progression biopsies (core biopsies); a cell block from a pleural effusion may be substituted for a core biopsy; in select cases, patients may be allowed to enroll without a pre-treatment biopsy and/or continue treatment without an on-treatment biopsy (even if a pre-treatment biopsy is obtained) after speaking with the sponsor if performing the biopsy is technically challenging, poses significant risk to the patient, or may result in significant discomfort
Prior treatment with pazopanib
Availability of curative treatment option for the patient’s cancer, whether surgery, chemotherapy, radiation, or combination thereof, unless the patient has documented refusal of curative treatment
Previous treatment with investigational gene or chimeric antigen receptor therapy.
prior treatment as follows:
Prior treatment with murine and hu3F8 is allowed
Prior treatment with irinotecan or temozolomide is permitted
Previous treatment with any radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used for labeling the respective radiopharmaceutical prior to the administration of study drug.
Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
Prior treatment with carotuximab (TRC105)
Current treatment on another therapeutic clinical trial
History of peptic ulcer within the past 3 months prior to study treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days prior to study treatment
Patients who were enrolled into any other treatment clinical trial and received treatment on that trial within 4 weeks of study treatment
Prior treatment with nab-paclitaxel (abraxane)
Inclusion Criteria\n\n          1. Histologic confirmation of metastatic NSCLC. For subjects with EGFR mutations, prior\n             therapy must have included an EGFR tyrosine kinase inhibitor. Subjects must not have\n             ALK rearrangement.\n\n          2. Availability of archival (diagnostic) specimens or willing to undergo a pre-treatment\n             biopsy.\n\n          3. Subjects with treated brain metastases must have been treated with surgery and/or\n             radiation therapy ? 21 days pre-study and must be clinically stable with no\n             requirement for steroids.\n\n          4. Laboratory parameters for vital functions should be in the normal range.\n\n          5. ECOG Performance Status ? 2.\n\n        Exclusion Criteria\n\n        Subjects may not enter the study if they fulfill any of the following criteria:\n\n          1. Treatment with an investigational agent within 4 weeks of starting treatment or prior\n             treatment with a checkpoint inhibitor (CTLA-4, PD-1 or PD-L1 antibodies).\n\n          2. Active, suspected or prior documented autoimmune disease, clinically significant\n             cardiovascular disease, or clinically uncontrolled hypertension.\n\n          3. History of pneumonitis or interstitial lung disease, or any unresolved immune-related\n             adverse events following prior therapy.\n\n          4. Major surgery within 4 weeks of starting treatment (or scheduled for surgery during\n             the projected course of the study) or prior cancer vaccine treatment or allogeneic\n             bone marrow transplantation.\n\n          5. Subjects who are immunosuppressed, including those with known immunodeficiency or have\n             active infection including tuberculosis or other serious illnesses.\n\n          6. Skin disease (e.g., psoriasis) that may prevent intradermal administration of the\n             vaccine into the target areas.
Have participated in a prior oregovomab clinical trial. Prior treatment with Hiltonol® does not exclude a subject from participation.
At least two sites of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; one of which must be amenable to treatment with SAR and accessible for a mandatory pre-treatment biopsy and a post-treatment biopsy at physician discretion; if a pulmonary nodule is being considered for SAR it must range in size from 1-5 cm
Has had prior treatment with pembrolizumab
Has had prior treatment with cabozantinib
Prior treatment with immune checkpoint inhibitors is allowed, provided that no treatment-related grade >= 3 adverse events (other than grade 3 endocrinopathy managed with replacement therapy) were observed and at least a minimum of 28 days have elapsed between the last dose of prior treatment and the proposed cycle 1 day 1
Documented disease progression (either radiographic or biochemical) on at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate prostate cancer or nonmetastatic (M0) CRPC.
Adult subjects with advanced MDS requiring treatment with HMA and either refractory to at least 4 cycles or progressing after previously documented response\r\n* Patient must be treated within 6 months of the last HMA treatment and must be willing to be treated with the same agent they last received on this study\r\n* Prior treatment with novel HMA analog of decitabine on clinical trial is allowed; in such cases, decitabine will be used as the standard of care agent
FOCBP and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period
Prior treatment with any therapy that is targeted to B cell maturation antigen (BCMA) or any other CD3-redirecting drug
No implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery in the investigator’s opinion
Subjects must not have implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery in the investigator’s opinion
No endoluminal stent in place at the time of treatment
Subject is receiving excluded therapy/treatment per protocol
Prior treatment with palbociclib
FOR ALL PHASES (Ib AND II): Concurrent treatment with postmenopausal hormone replacement therapy; prior treatment must be stopped for at least 28 days prior to first baseline biopsy
No restrictions on prior treatment to be eligible
Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational medicinal product (IMP) within ? 5 x the half-life of the IMP prior to day 1 cycle 1 of Minnelide.
Ability to cooperate with study treatment and follow-up.
Patients with prior known toxicity from IL-17A directed therapy, which led to discontinuation of the study treatment, will be excluded from CJM112 containing arms of the study.
Appropriate for treatment with sunitinib in the opinion of the treating physician
Subjects must have received intravesical treatment with at least two doses of BCG within six months of nivolumab treatment initiation
CRITERIA FOR SCREENING: For patients in stage 1 only, prior treatment with any CD19 CAR T-cell therapy is excluded
Willing to refrain from using other lotions, creams, etc. during the treatment period;
Abstinence from all manner of physical contact near the treatment area during and up to 2 weeks after the treatment phase.
Elective surgery for treatment of the cutaneous metastases during the study and up to 4 weeks after the treatment period. Cutaneous metastases are required to remain in-situ and measurable for up to 2 weeks after last treatment to achieve study objectives;
Participation in the treatment phase of another clinical trial within the four weeks prior to treatment in this clinical trial;
No prior treatment with ONC201
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Histologically documented differentiated thyroid cancer with or without metastases, not amenable to curative treatment; or the patient has documented refusal of curative treatment
Ability to comprehend the nature of the treatment
Prior treatment with axitinib
Previous treatment with talimogene laherparepvec or any other oncolytic virus
Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
At time of day 1 of protocol treatment, subjects with central nervous system metastases must have been treated and must be asymptomatic and meet the following:\r\n* No concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids\r\n* Neurologic stability (lack of signs and symptoms greater than baseline prior to x-ray therapy [XRT]) until the time of dosing\r\n* For radiation treatment, patients must not receive stereotactic radiosurgery or gamma knife treatment within 7 days of day 1 of protocol treatment; for whole brain radiotherapy (WBRT), there should be at least 28 days between last day of WBRT and day 1 of protocol treatment\r\n* Note: patients with leptomeningeal disease or cord compression are excluded from the study
Any previous treatment with a hypomethylating agent, including decitabine, azacitidine, or SGI-110
Prolonged antibiotic treatment (>= 10 days, within 3 weeks of enrollment) as prevention or suppression of an ongoing infection, where treatment involves gut-perturbing anti anaerobic antibiotics
Treated with or eligible to commence prophylactic treatment with a proton-pump inhibitor prior to implantation, and to continue to receive treatment for at least 6 months post implantation
Prior treatment with trabectedin
Patients with previous history of vandetanib or cabozantinib treatment for more than 28 days of treatment (patients have discontinued treatment for 28 days before enrolling)
Prior treatment with gene modified T cells
Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
Participant has received any prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment for Myelodysplastic Syndrome is allowed except for use of cytarabine.
Have received or are receiving an investigational medicinal product (IMP) or other systemic anticancer treatment within 2 weeks prior to the first dose of study treatment
Not suitable for SBRT treatment
Prior treatment with either decitabine or azacitidine
Patients may not have had prior radiotherapy (> 30 Gy) to the area requiring treatment that would result in any overlap of tissue in both fields
Patient who has had prior treatment with mistletoe
Patient who has had any prior radiotherapy to the treatment site(s)
Prior ALT-803
Prior treatment with either venetoclax or ibrutinib
Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 4 weeks prior to first administration of study treatment
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter the study
COHORT 1 (WITH SORFENIB): No previous systemic therapy including sorafenib or chemotherapy treatment; previous TACE and local treatments are permitted
Alemtuzumab treatment within 8 weeks of HSCT admission
Patients who are simultaneously enrolled in any other treatment study
PRE-SCREENING: No prior treatment with anetumab ravtansine (or any other mesothelin-based therapy)
Previous assignment to treatment during this study; patients permanently withdrawn from study participation will not be allowed to re-enter the study
Patients must not have had prior treatment of glioblastoma with stereotactic radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel).
Patients may not have undergone previous treatment with lomustine.
Has significant toxicities from prior treatment that have not resolved or stabilized
Prior treatment with cytotoxic drugs within 5 years of screening for any condition (example [e.g.], cancer, rheumatoid arthritis) or prior use of any anti-CD20 antibody
Per investigator's judgment, be eligible for treatment with valganciclovir.
Be receiving leflunomide, or artesunate when study treatment is initiated. Note: Subjects who may be receiving leflunomide must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Subjects receiving artesunate must discontinue the use prior to the first dose of study treatment.
Be on treatment with anti-CMV agents (ganciclovir, valganciclovir, foscarnet or cidofovir) for the current CMV infection for longer than 72 hours. Note: A subject who is receiving these anti-CMV agents must discontinue their use before the first dose of study treatment. A subjects who may be receiving cidofovir must discontinue this antiviral at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Note: Subjects who were administered these anti-CMV agents for prophylaxis, should have these treatments completed at least 2 weeks prior to the study entry or start of the treatment for current infection, whichever comes first and have undetectable CMV DNA (based on local laboratory) for at least two weeks between the completion of this treatment and onset of the current infection.
Prior treatment with all-trans retinoic acid (ATRA) or systemic retinoid for the treatment of hematologic malignancy.
Patients may concurrently receive bisphosphonates or rank ligand inhibitors while on this study if necessary for treatment or prevention of osteopenia or osteoporosis; prior treatment with LHRH agonists is allowed for premenopausal women; topical vaginal estrogen therapy is allowable
Tumor recurrence after previous treatment, which must have included at least radiation therapy and one cytotoxic chemotherapy; there is no limit on number of previous recurrences or lines of treatment
Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JCAR017 treatment in this protocol for subjects receiving retreatment
Treatment plan that includes post-transplant maintenance therapy
Prior treatment with any pan-HER TKI (eg, lapatinib, afatinib, dacomitinib, neratinib).
Unwilling or unable to discontinue disallowed disease-modifying antirheumatic drugs (DMARDs) for treatment of SSc prior to mobilization
Patients should be excluded if they have had prior treatment with cabozantinib; previous use of other antiangiogenic agents other than cabozantinib is allowed
Prior treatment with DCC-2618
Eligible to receive treatment with a CPI.
Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
Signs and symptoms of infection within 2 weeks of first study treatment; receipt of therapeutic oral or IV antibiotics within 2 weeks of first study treatment; subjects receiving routine antibiotic prophylaxis (for dental extractions/procedures) are eligible
Prior treatment with any LAG-3 targeting biologic or small molecule
Prior treatment with idelalisib
Previous treatment with any weekly taxane regimen.
No prior treatment with carmustine wafers
Have been informed of other treatment options
Prior treatment with fosbretabulin is allowed, if not given in combination with everolimus
Previously untreated for myeloma or have received no more than one cycle of any treatment regimen; NOTE: Prior radiation therapy for the treatment of solitary plasmacytoma is permitted; prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
The use of hydroxyurea before enrollment is permitted; hydroxyurea should be discontinued prior to start of study treatment; patients with symptoms/signs of hyperleukocytosis or white blood cell count (WBC) >100,000/uL can be treated with leukapheresis or may receive up to 1 dose of cytarabine (up to 500 mg/m^2) anytime prior to enrollment
The following patients are allowed:\r\n* Patients may have been treated for AML or antecedent hematologic disorder with myeloid growth factors, recombinant erythropoietin, thalidomide, lenalidomide, 5-azacitidine or decitabine\r\n* Any prior chemo therapy must have been completed >= 2 weeks prior to day 1 of study treatment and the participant must have recovered to eligibility levels from prior toxicity\r\n* There is no limit for prior chemo regimens\r\n* Patients may have received hematopoietic stem cell transplantation for AML or other diseases\r\n* Hydroxyurea is allowed prior to day 1 of study treatment for count control and during cycle 1; the use of hydroxyurea is not allowed beyond completion of cycle 1
Prior treatment with lenvatinib
Active treatment for VTE
Any prior systemic anti-cancer immunotherapy treatment
Signed and dated PICF obtained prior to initiation of any study-specific procedure and treatment.
Prior treatment or preventative use of any hormonal agent such as aromatase inhibitors (AI), fulvestrant, raloxifene, tamoxifen or other SERM, or with any other hormonal agent used for the treatment or prevention of BC or for any other indication (e.g. osteoporosis).
Prior radiotherapy that would result in overlap of radiation treatment fields with planned treatment for study cancer.
Prior systemic treatment must be completed at least 14 calendar days prior to registration and the subject must have recovered from the toxicities of treatment to grade 1 or better
Previous treatment information (name of agent, treatment starting date, and date of progression) must be available for review
Unavailable for follow-up visits after treatment
Dose expansion - KRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. BRAF mutant patients group: Prior treatment with an ERKi and/or a pan-RAFi.
At enrollment, patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy\r\n* Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids and/or lenalidomide and/or bortezomib/principal investigator (PI)-based regimens does not disqualify the subject (the corticosteroid treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle of lenalidomide and/or PI-based therapy)
Be willing to undergo normal skin biopsy prior to initiation of treatment and after treatment
Cardiac testing with either exercise stress test or thallium stress test, within 3 months of start of the first treatment day; atrial fibrillation that is rate controlled is allowed; note – the first treatment day is about 9 weeks before the first IL-2 treatment day; if a cardiologist’s evaluation determines that this is superfluous based on other assessments, then this may be omitted
Prior decitabine for the treatment of this cancer; patients with previous exposure to therapy with gemcitabine are allowed in the study
Leptomeningeal involvement regardless of treatment status
Patients who have the following risk factors are considered to be at increased risk for cardiac toxicities and may be enrolled only with increased monitoring: i) prior treatment with anthracyclines; ii) prior treatment with trastuzumab; iii) a New York Heart Association classification of II controlled with treatment; iv) prior central thoracic radiation therapy (RT), including RT to the heart
Must be treated per protocol to lesion(s) of a single abdominal site that can reasonably be encompassed within a single treatment field; treatment of additional site(s) outside of the abdomen while the patient is on trial is acceptable
Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial
Leptomeningeal involvement regardless of treatment status
Have documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib; intolerance to sorafenib is defined as: Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 drug-related adverse event(s) which both a) persisted in spite of comprehensive supportive therapy according to institutional standards and b) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level; patients treated on sorafenib as the last treatment may start pembrolizumab at least 14 days after the last dose of sorafenib
Patient has received enzalutamide for the treatment of prostate cancer; however, previous treatment with other hormonal therapy (bicalutamide, abiraterone, ketoconazole, flutamide, and nilutamide) or chemotherapy (docetaxel, cabazitaxel, or mitoxantrone) is allowed
Subjects must have failed hypomethylating treatment where \failure\ is defined as: Progression (according to 2006 International Working Group [IWG] criteria) at any time after initiation of the hypomethylating treatment OR Failure to achieve complete or partial response or hematological improvement (HI) (according to 2006 IWG) after at least 4 cycles treatment OR Relapse after initial complete or partial response or HI (according to 2006 IWG criteria).
Prior treatment with temozolomide, dacarbazine or procarbazine
Current treatment with agents that may prolong QT interval and may cause Torsade de Points which cannot be discontinued at least five half-lives prior to treatment
Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index
Treatment within 14 days prior to first study treatment with conventional therapy or treatment within 28 days prior to first study treatment with an investigational drug
Patients receiving cytotoxic agent as immunomodulatory therapy for a non neoplastic indication (e.g. methotrexate for rheumatoid arthritis) and who are unable to discontinue such agents within 2 weeks prior to starting treatment
FOCBP and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period
Patient is currently receiving clinical benefit from the treatment with IMCgp100, as determined by the principal investigator from the parent study
Has prior treatment using an anthracycline
A blood pressure (BP) =< the 95th percentile for age, height and gender despite optimal antihypertensive treatment within 7 days of the first dose of the study treatment; please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
Have been informed of other treatment options and is not a candidate for standard treatment options or stem cell transplant at the time of enrollment
Prior DNA methyl transferase inhibitor administration (azacitidine, decitabine or guadecitabine) for AML or for antecedent MDS is allowed if this clinical trial is considered the best treatment option, but azacitidine, decitabine or guadecitabine must have been stopped at least 3 weeks prior to day 1 of treatment on the study
Participants are required to stop receiving myeloid growth factors at least 1 week (Neupogen) or 2 weeks (Neulasta) before starting treatment on the study
Hyperleukocytosis with > 50,000 blasts/ul; hydroxyurea for blast count control is permitted before starting treatment, but must be stopped prior to starting treatment on the study; patients will be withdrawn from the study if > 50,000 blasts/ul occur or recur > 14 days after starting treatment on the study
Previous treatment with talazoparib
Patient is a candidate for a maximum of one further line of established therapy (prior to treatment with ACTolog).
Patients having received prior radiotherapy, treatment with cytotoxic agents, treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy within the 4 weeks prior to treatment with selinexor, or those who have not fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment)
Previous brentuximab treatment
Patients not previously treated for their FL, including any previous treatment for FL under clinical trials except localized radiation therapy for previous limited stage disease.
Patient has received niclosamide, abiraterone or ketoconazole for the treatment of prostate cancer; however, previous treatment with other hormonal therapy (bicalutamide, enzalutamide, flutamide and nilutamide) or chemotherapy (docetaxel, cabazitaxel or mitoxantrone) is allowed
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted; prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is > 3 years
Treatment with radiation therapy within 12 weeks prior to the first dose of study treatment, unless there is tissue confirmation of tumor recurrence or there is progression outside the treatment field
Prior treatment with intracystic P-32 or intracystic bleomycin
Patients must have newly diagnosed AML or ALL without previous treatment; hydroxyurea will be allowed to control peripheral blast count as clinically indicated but would need to be stopped prior to initiation of tyrosine kinase inhibitor [TKI]); all-trans retinoic acid (ATRA) is permitted during the period prior to ruling out a diagnosis of APL; previous radiation treatment is allowable; patients must be deemed eligible for treatment with cytotoxic induction chemotherapy with cytarabine and idarubicin for AML or hyper-cyclophosphamide, dexamethasone, doxorubicin, vincristine sulfate (CVAD) for ALL; patients newly diagnosed with ALL must have received no prior treatment for their ALL with the exception of steroids (i.e. prednisone, dexamethasone); intrathecal methotrexate or cytarabine, allowed prior to and throughout the enrollment period for AML and ALL
Concurrent opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system; patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
Documented infections or oral temperature > 38.2 degree Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance therapy; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
Have received treatment with any form of therapy with CYP17 inhibitory activity such as ketoconazole, aminoglutethimide, or an antiandrogen such as bicalutamide within 6 months of study treatment initiation
mCRPC EXPANSION COHORT: Patients must have received prior treatment with enzalutamide and/or abiraterone with the exception of patients who were treated with docetaxel and androgen deprivation therapy for metastatic castrate-sensitive prostate cancer and progressed on docetaxel treatment or who progress within one month of the last docetaxel dose
mCRPC EXPANSION COHORT: The patient has received radionuclide treatment within 6 weeks prior to the first dose of the study treatment
If a curative treatment option in the form of chemoradiation exists in a patient with unresectable disease, this has to be attempted first and must have failed, unless the patient has documented refusal of curative treatment
Availability of curative treatment option for the patient’s cancer, whether surgery, chemotherapy, radiation, or combination thereof, unless the patient has documented refusal of curative treatment
If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least four weeks prior to the first dose of ARQ 751. a. Initiation of bisphosphonates during the study may be allowed provided the subject completes the first cycle of treatment without any dose limiting toxicity (DLT) and the Investigator rules out tumor progression.
Prior treatment with venetoclax or ibrutinib
Received prior treatment or receiving current treatment for this malignancy
If the patient has been using the Optune™ device, it will be discontinued before initiating treatment with either study medication, and per inclusion criterion listed above, the patient must have recovered from all treatment-related toxicities to Grade 1 or less.
Patients must be >= 14 days from previous cytotoxic treatment
Prior treatment with any CD19 CAR T-cell therapy
Any prior treatment with: ipilimumab
PRIOR TO LYMPHODEPLETION: Available autologous T cells with ? 15% expression of CD30CAR determined by flow cytometry required prior to treatment with ATLCAR.CD30 cells
Treatment plan that includes regional nodal irradiation
Unstable ventricular arrhythmia requiring treatment
There is no limit on the number of prior treatment regimens
Use of any active treatment for relapse/refractory AML including but not restricted to chemotherapy, targeted agents, hypomethylating agents or investigational drugs; use of hydroxyurea up to 6g per day for cytoreduction is allowed for a maximum of 15 days prior treatment
Patient is a candidate for, and agrees to proceed with additional bevacizumab treatment.
In first or subsequent relapse, or refractory to the last treatment (defined as less than a complete metabolic response to the last treatment, or within 6 months from the last treatment).
Treatment with plasmapheresis within 4 weeks prior to event 1
Current or previous treatment with investigational therapy in another therapeutic clinical trial interrupted less than 4 weeks before study treatment initiation.
Have been informed of other treatment options
Prior treatment with murine and hu3F8 is allowed; patients with prior humanizing murine IgG3 anti-GD2 antibody m3F8 (m3F8), hu3F8, ch14.18 or hu14.18 treatment must have human anti-human antibody (HAHA) antibody titer < 1300 enzyme-linked immunosorbent assay (ELISA) units/ml; human anti-mouse antibody positivity is allowed
Patients must not be pregnant at the time of SRS treatment
Prior radiotherapy that precludes the proposed treatment with hypofractionated radiotherapy
Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the study drugs; if such drugs have been used, patients must have discontinued these agents at least 2 weeks (or as noted below) prior to initiating study treatment; examples include:\r\n* STRONG CYP3A4 inducers \r\n* Immunosuppressants (e.g., tacrolimus, leflunomide, tofacitinib, roflumilast, pimecrolimus)\r\n* NSAIDs\r\n** Note: NSAIDs must be discontinued within 5 days prior to initiating study treatment
Patients must require systemic treatment
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
Scheduled to undergo radioembolization for treatment of intrahepatic metastases
This study permits the re-enrollment of a patient who has discontinued the study for a reason other than treatment failure or adverse event(s) of the study treatment; the patient must be re-consented and assigned a new subject number
Current active treatment in another clinical study
Prior therapy with abiraterone, enzalutamide and/or docetaxel; there is no limit to the number of prior treatment regimens
Previous therapy with rabbit anti-thymocyte globulin (ATG); previous treatment with equine ATG is allowed if more than 3 months ago \r\n* Note: previous myeloablative autologous transplant is permitted but not required
Male who is expecting to father a child during the treatment period
CAPMATINIB INCLUSION CRITERIA: Prior treatment with at least one Food and Drug Administration (FDA)-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
CERITINIB INCLUSION CRITERIA: Prior treatment with at least one FDA-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
REGORAFENIB INCLUSION CRITERIA: Prior treatment with at least one FDA-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
ENTRECTINIB INCLUSION CRITERIA: Prior treatment with at least one FDA-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
Prior treatment with anthracyclines
No prior receipt of systemic treatment (chemotherapy, targeted therapy, or immunotherapy) for the lesion under consideration of treatment
Patient received investigational treatment within 2 weeks or immunotherapy or antibody therapy within 28 days prior to initiation of treatment with Toca 511, and/or has not recovered from toxicities associated with such treatment.
Scheduled to undergo either partial or radical nephrectomy as part of treatment plan
No implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery, in the investigator’s opinion
Participants must have received at least one but no more than six prior treatment regimens. Prior treatment with an anti-CD20 agent, either alone or in combination, is allowed.
Either: \r\n* Relapsed after or refractory to prior treatment with at least two regimens or lines of treatment\r\n* Prior failure of at least one regimen or line of treatment, with poor cytogenetic or other risk factors, and ineligible for other clinical trials
No more than 2 prior induction regimens (excluding prior HSCT) in their first line treatment and one must have included cytarabine with an anthracycline (or anthracenedione)
Prior treatment with an Murine Double Minute 2 (MDM2) antagonist
No more than 3 prior progressions
COHORT II: Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment)
Willingness to provide a fresh biopsy prior to study enrollment and after 2 cycles of treatment as clinically appropriate per PI discretion
Refractory to or relapsed after at least 1 prior treatment regimen
Must consent to study-specific biopsies at two separate timepoints: pre-treatment (Screening) and post-treatment (Day 28 or EOS).
For hypomethylating failure cohorts, treatment for MDS with any other drug not being an HMA with the following exceptions: prior treatment with growth factors and/or lenalidomide is allowed for any cohort
Prior treatment with carfilzomib
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:
Prior treatment with cabozantinib
No prior systemic treatment for acute GVHD except for a maximum of 3 days of prednisone (or IV methylprednisolone) ? 2 mg/kg/day; topical skin steroid treatment, non-absorbable oral steroid treatment for gastrointestinal (GI) GVHD, and resumption of GVHD prophylaxis agents (e.g., calcineurin inhibitors) are permissible; patients enrolled in BMT CTN 1501 who randomized to sirolimus are also eligible
Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study. Patients who progress on placebo are specifically allowed to enroll on the treatment arm of the study if they meet all other entry criteria
Have a history of intolerance, hypersensitivity, or treatment discontinuation due to severe immune adverse events on prior immunotherapy, or documented presence of neutralizing anti-drug antibody to nivolumab, ipilimumab, or pembrolizumab. Subjects who discontinued prior immunotherapies for immune-related adverse events that are well-controlled with appropriate treatment may be enrolled if approved by the Medical Monitor.
Have current second malignancy at other sites, which requires treatment, or in the judgement of the Investigator, may require treatment within the next year. Concurrent malignancies that do not require treatment and are clinically stable are allowed. A past history of other malignancies is allowed as long as the subject is not receiving specific treatment other than hormonal therapy, and, in the judgement of the Investigator, is unlikely to have a recurrence.
Must meet one or more of the consensus criteria for initiating treatment MM Participants:
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy and failed last line of treatment (disease progression ?60 days of completion of last therapy)
Prior treatment with an anti-ErbB3 antibody
Previous treatment with farletuzumab or other folate receptor targeting agents
For subjects being enrolled to receive PLD plus carboplatin, prior treatment with anthracyclines or anthracenodiones
There is no limit to the number of prior treatment regimens provided that performance status and life expectancy meet the criteria above
All participants will be required to undergo mandatory pre and on-treatment biopsies
Subjects must not: have active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis); require treatment with an antiherpetic drug; have received live-virus vaccination within 30 days of planned treatment start; have previous therapy with talimogene laherparepvec, oncolyic viruses, or tumor vaccine.
Prior treatment with leflunomide
Current or planned growth factor or transfusion support until after initiation of treatment; if growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
Prior treatment with other anti-GD2 antibodies is allowed (prior treatment with hu3F8 is NOT allowed), but human anti-human antibody (HAHA) antibody titer must be =< 1300 enzyme-linked immunosorbent assay (ELISA) units/mL
TURNSTILE II - TREATMENT:
TURNSTILE II - TREATMENT
Prior treatment with abiraterone or enzalutamide is permitted, but patients must have been off prior corticosteroid treatment for at least 3 months
Systemic oral corticosteroid treatment within 28 days prior to initiating treatment on study except as detailed above
No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 2 weeks prior to treatment with CPI-613; hydroxyurea and oral tyrosine kinase inhibitors being used without grade =< 2 toxicity can be taken until day 1 of therapy; patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, non-hematologic, non-infectious toxicities from prior treatment =< grade 2 are eligible, but must be documented as such
Subjects in whom treatment planning constraints cannot be met
Subjects in whom treatment planning constraints cannot be met
There is no limit to the number of prior systemic treatment regimens
Current treatment on another clinical trial
If a subject is currently receiving bisphosphonates or denosumab, the subject must have received the bisphosphonates or denosumab for at least four weeks before starting study treatment. (Initiation of bisphosphonates or denosumab during the study may be allowed provided the subject completes the first cycle of treatment without any DLT and the Investigator rules out tumor progression.)
For subjects enrolled in the Anastrozole Arm, prior hormonal therapy (including, but not limited to, tamoxifen, megestrol acetate, fulvestrant, and GnRH analogs) for the treatment of recurrent/advanced endometrial cancer are not allowed
Contraindications to treatment with:
Contraindication to antiangiogenic agents, including:\r\n* Serious non-healing wound, non-healing ulcer, or bone fracture\r\n* Major surgical procedure or significant traumatic injury within 4 weeks prior to initiating study treatment\r\n* Pulmonary hemorrhage/bleeding event >= grade 2 within 12 weeks prior to initiating study treatment\r\n* Any other hemorrhage/bleeding event >= grade 3 within 12 weeks prior to initiating study treatment
Prior treatment with anti-androgens other than enzalutamide is acceptable
Prior treatment with enzalutamide
Previous radioimmunotherapy. Previous antibody-based therapy is allowed as long as ? 28 days has elapsed from last dose to study treatment.
Subject has any underlying conditions, which would contraindicate therapy with study treatment
Must have had prior abiraterone treatment
Major active medical or psychosocial problems that could be exacerbated by the study treatment
One or more evaluable or measurable lesions that have progressed based on RECIST 1.1, within 12 months of 131 iodine therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning. These participants must not be eligible for possible curative surgery; or
Previous treatment with lenvatinib (except for participants previously enrolled into Cohorts 1 or 2B of this study).
Prior treatment with TRC105
Current treatment on another therapeutic clinical trial
Received ? 1 typical regime for the treatment of ITP. Splenectomy is considered one standard ITP treatment
At least two sites of measurable disease as defined by RECIST 1.1; one of which must be amenable to treatment with SAR and accessible for optional pre- and post- treatment biopsy; if a pulmonary nodule is being considered for SAR it must range in size from 1-5 cm
Have provided written consent for mandatory pre- and post-treatment biopsy (expansion cohort only)
Prior treatment with crenolanib with progression on treatment
Prior treatment with talazoparib
Patients with curative treatment options
No prior treatment for myelofibrosis (for cohort 1 only)
Prior treatment with copanlisib
Prolymphocytic leukemia (PLL) T-cell (T)-CLL\r\n* T-PLL: treatment failure after Campath-1H and at least one other regimen\r\n* B-PLL: treatment failure after fludarabine and at least one other salvage regimen
Planned ongoing treatment with other drugs thought to potentially adversely interact with study drugs; if such medications have been used, patients must be off of these agents for >= 2 weeks prior to initiation of treatment:\r\n* Anticoagulants at therapeutic doses\r\n* Immunosuppressants such as tacrolimus, leflunomide or tofacitinib, roflumilast, pimecrolimus
Prior chemotherapy treatment for AML within 21 days from the initiation of HCT conditioning; Note, use of hydroxyurea or other low intensity treatment not intended to induce remission are acceptable
Patients must agree to pre- and post-treatment biopsies
Prior treatment with cabozantinib
Received radionuclide treatment (i.e. iodine [I]-131 meta-iodo-benzyl guanidine) within 6 months of the first dose of study treatment
Patient will have opted for SBRT among definitive treatment choices
TREATMENT: Patients receiving systemic corticosteroid within 48 hours of CTL infusion
Prior local therapy, such as surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment; local therapy must have been completed at least 4 weeks prior to the baseline scan
Any condition that requires or is likely to require treatment with systemic corticosteroids within the core study period and short term follow-up
Subjects with any underlying conditions, which would contraindicate therapy with, study treatment (or allergies to reagents used in this study)
Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
Interested in treatment that might change smoking behavior
Enrolled in another treatment protocol
Patients must be a minimum of 3 weeks from thoracotomy (if performed) and well-healed before starting treatment
Prior treatment with topotecan.
Prior treatment with cytotoxic and biological agents is permissible; there should be at least a 2-week break between prior treatment and the protocol treatment
One prior single fraction radiosurgical procedure within the treatment field is acceptable if V12 < 5 cc (V12 is the volume of normal brain [outside gross tumor volume (GTV)] receiving 12 or more Gy); additional radiosurgical procedures outside of the treatment area are acceptable
Patients who are simultaneously enrolled in any other treatment study
Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment; note: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on sonidegib study treatment
Prior treatment with cabozantinib or other c-MET directed therapy
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
Receipt of 1 previous systemic drug therapy for at least 3 weeks and withdrawal from treatment due either to intolerability or to radiographic disease progression. If treatment was withdrawn due to intolerability manifested as a Grade 3 or 4 event by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE v4.0), less than 3 weeks of continuous prior administration prior to withdrawal is acceptable (see also Exclusion Criterion #3).
Locoregional treatment within 4 weeks prior to the Baseline Visit.
Previous treatment with lenalidomide for AML
Prior allograft or prior autograft
Prior treatment with bevacizumab
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Have body temperature >101ºF (38.3ºC) immediately prior to study treatment.
For Cohorts A and B, patients must have progressed on prior treatment with enzalutamide or abiraterone acetate + prednisone (by PSA criteria or radiographically)
For Cohort C (castration-only):\r\n* Patients must continue on castrating therapy throughout BAT treatment\r\n* No prior second line hormone treatment with flutamide, bicalutamide, nilutamide, enzalutamide, abiraterone, ketoconazole, ARN-509 or other investigational androgen ablative therapies is permitted for Cohort C
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; nota bene (NB): muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments
Previous treatment with sunitinib or valproic acid for uveal melanoma
Participants in the study must permit targeted prostate biopsy prior to initiation of study treatment and at the time of fiducial marker placement
Concomitant administration of investigational drugs is not allowed; if investigational drugs were given, their use should be completed as guided by that protocol prior to initiation of cytoreduction on this protocol; if the patient is being treated for secondary (treatment related) myelodysplasia after treatment for a non-hematologic malignancy (e.g. Sarcoma), the primary disease should be in remission for at least 6 months after completing primary therapy; patients with secondary myelodysplasia after treatment of a lymphoma, may proceed with treatment with the lymphoma responding or stable but not progressing
No prior treatment with oxaliplatin, irinotecan (irinotecan hydrochloride), fluorouracil or capecitabine
Prior treatment with cabozantinib
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
UGT1A1 genotyping prior to treatment
Refractory to or relapsed after at least 1 prior treatment regimen
Local-regional treatment sites must be able to be encompassed within a reasonable radiation therapy treatment volume
Patients must agree to have a biopsy at baseline and on treatment
Patient who has had prior treatment with demethylating agents
Prior use of venlafaxine specifically for treatment of pain (prior use for treatment of other indications, such as hot flashes, is permitted)
Patient receiving treatment likely to cause hemolysis or under phenytoin treatment.
Only patients that have not received any prior treatment for pancreas cancer are eligible for this treatment protocol
RANDOMIZED PHASE II (ARMS K AND L): Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
Patient must be eligible for HD IL-2 treatment
Relapsed/refractory MCL: Prior treatment with ibrutinib
Prior decitabine for the treatment of cancer
Prior treatment with capecitabine or lapatinib
Biologic therapy (including antibodies [other than trastuzumab], immune modulators, cytokines) within 4 weeks before the first dose of study treatment; Note: there is no washout period required for trastuzumab
Prior treatment with omacetaxine
There will be no limits to prior lines of treatment
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
Patients who have had prior treatment with 131I-MIBG who do not meet the re-treatment criteria
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted
Patients must be willing to participate in all stages of treatment
Patient is currently benefiting from the treatment with pasireotide, as determined by the investigator
Prior treatment with murine and humanized 3F8 is allowed; patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have human anti-human antibody (HAHA) antibody titer =< 1300 enzyme-linked immunosorbent assay (Elisa) units/ml; human anti-mouse antibody positivity is allowed
Prior to enrollment, sites must provide evidence of myeloma progression/relapse and evidence of being refractory to lenalidomide, with start and stop dates of lenalidomide therapy and the most recent treatment regimen, as well as best tumor response to all prior treatment regimens
Able to receive outpatient treatment and follow-up at the treating institution.
Prior treatment with eribulin
Allocated to receive Gemcitabine + nab-Paclitaxel as first line treatment.
COHORT 3: ATOPIC DERMATITIS PATIENTS: Prior to initiation of randomized treatment, subjects must have signs of bacterial skin infections (skin weeping, crusting, and/or pustules)
Potassium in normal range\r\n* Patients with hypokalemia at screening must be corrected prior to initiating treatment
Patients must not have had prior treatment with floxuridine (FUDR)
Prior thoracic radiation allowable only if there is minimal to no overlap with the treatment area estimated at the time of consultation
However, abnormalities of specific organs will not be considered grounds for exclusion if they are the result of the EBV+ malignancy or its treatment (e.g. a renal allograft recipient with an EBVLPD may be on dialysis because the allograft was rejected when the immune suppression was stopped as a first approach to treatment of the EBVLPD); a the discretion of the investigator, patients with elevated but stable creatinine will not be precluded from treatment on study
Able to tolerate pre / post - procedure steroid treatment
Temozolomide re-treatment is planned by the treating neuro-oncologist
Concurrent opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system; patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
Prior history of treatment with ponatinib
Prior treatment with murine 3F8 is allowed; patients with prior m3F8, chimeric (ch)14.18 or hu14.18 treatment must have human anti-hu3F8 antibody (HAHA) antibody titer less than the upper limit of normal (defined as mean + 3*standard deviation [SD] of normal volunteers)
Prior systemic treatment with an azole anti-fungal drug (e.g. fluconazole, itraconazole) within 4 weeks of cycle 1, day 1
Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate and/or enzalutamide) for the treatment of mCRPC.
Prior treatment with agents targeting the VEGF pathway, including bevacizumab
Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine.
Previous systemic anti-cancer therapy for T-cell lymphoma must have been discontinued at least 3 weeks prior to treatment; for the dose expansion phase, in progressing subjects, a 2 week washout may be allowed after discussion with Memorial Sloan-Kettering (MSK) principal investigator
Has been treated with an Somatostatin analogs (SSA) at any time prior to randomization, except if that treatment was for less than 15 days (e.g. peri-operatively) of short acting SSA or one dose of long acting SSA and the treatment was received more than 6 weeks prior to randomization
Patients must have an ECOG PS of 0-1 at screening and on the day prior to treatment.
Not currently a candidate for curative treatment
Received an immune-suppressive based treatment for any reason within 14 days prior to the first dose of study treatment.
Must not have experienced an immune-related adverse event (irAE) where the irAE was the reason for permanent discontinuation of prior immunotherapy in the most recent prior treatment regimen
Patients currently receiving chronic corticosteroid treatment (longer than 8 weeks duration) for management of pre-existing adverse events, or patients with a history of chronic corticosteroid treatment longer than 8 weeks' duration for AEs within 6 months of Screening are excluded
Adults with AML in need of treatment
Unable to receive prophylactic treatment for pneumocystis
TREATMENT:
Prior treatment with irinotecan and/or bevacizumab
Patients receiving chronic treatment with systemic steroids; however, patients can receive up to 10 days of steroid therapy prior to starting treatment with brentuximab vedotin (BV)+ doxorubicin, vinblastine, dacarbazine (AVD)
Treatment plan that includes regional nodal irradiation
No implanted hardware or other material that would prohibit appropriate treatment planning or treatment delivery, in the investigator’s opinion
Systemic oral corticosteroid treatment within 28 days prior to initiating treatment on study
Prior treatment with other immunotherapy, including antibodies, is allowed
Patients cannot take any additional vitamin D supplementation during study treatment; patients taking > 2000 IU per day prior to treatment will be ineligible
Additional treatment for NHL administered from time of autologous SCT through registration
Patients must be or have been ambulatory within a week prior to treatment
No planned systemic treatment is allowed within one week after treatment
Patients must be willing to participate in all stages of treatment
Subjects must have an indication for treatment as defined by the NCI Working Group Guidelines
Life expectancy reasonably adequate for evaluating the treatment effect
Prior treatment with idelalisib
Patients demonstrating disease progression after treatment with approved therapies that are known to confer life-prolonging benefit, or who are intolerant to or have declined treatment
Previous treatment with gene therapy
Patient has had previous treatment with poziotinib.
Febrile neutropenia or serious persistent infection within 2 weeks prior to Day 1 of treatment
Ongoing or previous anti-cancer treatment within 4 weeks before randomization.
Previous treatment with ixazomib, or participated in a blinded study with ixazomib
Refractory to or relapsed after at least 1 prior treatment regimen
Refractory to first or later treatment, or
Previous treatment with any anti-CD40 antibody.
Prior treatment with anti-lymphocyte globulin or anti-thymocyte globulin
Prior treatment for rectal cancer.
Current treatment of at least 3 months with pembrolizumab or nivolumab (no more than 1 cycle / 6 weeks of treatment interruption immediately prior to study enrollment)
Patients in which treatment with pembrolizumab and nivolumab is contraindicated
Patients must have received prior treatment with an immunomodulatory drug (IMiD) (for ?2 cycles or ?2 months of treatment) and a proteasome inhibitor (PI) (for ?2 cycles or ?2 months of treatment).
Planned neoadjuvant chemoRT treatment must conform to NCCN guidelines.
Inclusion Criteria:\n\n        Cohort A (Solid Tumours)\n\n          -  Age >= 18 years (>=20 years for Japan only) at screening\n\n          -  Signed and dated written informed consent in accordance with GCP (Good Clinical\n             Practice and local legislation prior to admission to the trial\n\n          -  WHO/ECOG (World Health Organization / Eastern Cooperative Oncology Group) performance\n             status 0-1 assessed at screening\n\n          -  Patient must be able to swallow oral capsules.\n\n          -  Male or female patients ready and able to use highly effective methods of birth\n             control during the study and for 12 weeks following the last dose of abemaciclib per\n             ICH (International Conference on Harmonization) M3(R2) that result in a low failure\n             rate of less than 1% per year when used consistently and correctly. A list of\n             contraception methods meeting these criteria is provided in the patient information.\n             Women of childbearing potential must have a negative serum pregnancy test at\n             screening.\n\n          -  Patients with histologically or cytologically confirmed diagnosis of advanced and/or\n             metastatic, measurable or evaluable, non-resectable solid tumours\n\n          -  Patients must have received and failed, or have been intolerant to, all treatment\n             known to confer clinical benefit or have no therapeutic options available as deemed\n             appropriate by their treating physician\n\n          -  Life expectancy >= 3 months in the opinion of the investigator assessed at screening;\n\n        Cohorts B, C, D, F (Breast Cancer):\n\n          -  Age >= 18 years (>=20 years for Japan only) at screening\n\n          -  Signed and dated written informed consent in accordance with GCP and local legislation\n             prior to admission to the trial\n\n          -  WHO/ECOG performance status 0-1 assessed at screening\n\n          -  Patient must be able to swallow oral capsules.\n\n          -  Women who have postmenopausal status due to either surgical/natural menopause or\n             chemical ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1)\n             with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin or\n             radiation-induced ovarian suppression\n\n               -  postmenopausal status defined as meeting one of the following conditions:\n\n                    -  prior bilateral oophorectomy\n\n                    -  age >= 60 years\n\n                    -  age < 60 years and amenorrheic (non-treatment-induced amenorrhea secondary\n                       to tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least\n                       12 months; and follicle stimulating hormone (FSH) and estradiol within the\n                       postmenopausal range as per institutional reference ranges.\n\n               -  Postmenopausal status due to radiation-induced ovarian suppression must be\n                  confirmed by FSH and estradiol level in the postmenopausal range\n\n          -  Histologically or cytologically proven diagnosis of breast cancer with evidence of\n             locally advanced or metastatic disease not amenable to resection or radiation\n\n          -  HR+ (local lab results at screening or, if not available, at the time of diagnosis) To\n             fulfil the requirement of HR+ disease, the primary tumour or metastatic lesion of the\n             breast cancer must express at least one of the hormone receptors (estrogen receptor\n             [ER] or progesterone receptor [PgR]) by immunohistochemistry (IHC). Estrogen receptor\n             and PgR assays are considered positive if there are at least 1% positive tumour nuclei\n             in the sample as defined in the relevant American Society of Clinical Oncology\n             (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010).\n\n          -  HER2 negative (local lab results at screening or, if not available, at the time of\n             diagnosis) as defined by the most recent American Society of Clinical Oncology\n             (ASCO)/College of American Pathologists (CAP) Guidelines (Hammond et al. 2010).\n\n          -  Previous adjuvant and neoadjuvant chemotherapy is permitted. 0-2 prior lines of\n             chemotherapy for the metastatic setting are allowed.\n\n          -  At least 1 lesion (measurable or non-measurable) that can be accurately assessed at\n             baseline with CT or MRI or PET-CT (CT portion of diagnostic quality) and which is\n             suitable for accurate repeated measurement. For Cohort F only: patients should have at\n             least one measurable lesion.\n\n          -  Cohort B, C, D, F Must be eligible for the corresponding hormonal therapy (letrozole,\n             anastrozole or fulvestrant). For Cohorts B and C previous treatment with fulvestrant\n             or exemestane is allowed. For Cohort D and F prior therapy with non steroidal\n             aromatase inhibitors (anastrozole, letrozole) or exemestane are permitted\n\n          -  Cohort F only: Postmenopausal with locally advanced or metastatic HR+ breast cancer\n             and refractory to aromatase inhibitors therapy and CDK4/6 inhibitor treatment (e.g.,\n             palbociclib or ribociclib) for locally advanced or metastatic breast cancer.Resistance\n             to aromatase inhibitors therapy is defined as the following:\n\n               -  disease recurrence while on, or within 12 months of end of adjuvant treatment\n                  with letrozole, anastrozole, or exemestane;\n\n               -  or disease progression while on, or within one month of end of letrozole,\n                  anastrozole, or exemestane.\n\n        Cohort E (NSCLC (Non-Small Cell Lung Cancer)):\n\n          -  Age >= 18 years (>=20 years for Japan only) at screening\n\n          -  Signed and dated written informed consent in accordance with GCP and local legislation\n             prior to admission to the trial\n\n          -  WHO/ECOG performance status 0-1 assessed at screening\n\n          -  Patient must be able to swallow oral capsules.\n\n          -  Male or female patients ready and able to use highly effective methods of birth\n             control during the study and for 12 weeks following the last dose of abemaciclib per\n             ICH M3 (R2) that result in a low failure rate of less than 1% per year when used\n             consistently and correctly. A list of contraception methods meeting these criteria is\n             provided in the patient information. Women of childbearing potential must have a\n             negative serum pregnancy test at screening.\n\n          -  Histologically or cytologically confirmed diagnosis of stage IV NSCLC.\n\n          -  The participant must have progressed after platinum-based chemotherapy AND\n             immunotherapy (unless deemed inappropriate candidates for immunotherapy by their\n             treating physician) AND have received a maximum of 2 other prior chemotherapy for\n             advanced and/or metastatic disease OR must be judged by the physician as ineligible\n             for further standard second-line chemotherapy. Prior treatment with epidermal growth\n             factor receptor-tyrosine kinase inhibitor (EGFR-TKI) and anaplastic lymphoma kinase\n             (ALK) inhibitors is mandatory in participants whose tumour has EGFR-activating\n             mutations or ALK translocations. Prior targeting agents and neoadjuvant/adjuvant\n             therapies are permitted.\n\n          -  Have adequate organ function including haematology, renal, and liver.\n\n          -  Have measureable disease per Response Evaluation Criteria In Solid Tumours (RECIST)\n             1.1.\n\n        Exclusion Criteria:\n\n        All cohorts:\n\n          -  Any documented active or suspected malignancy or history of malignancy, other than the\n             disease under study, within 3 years prior to screening, except appropriately treated\n             basal cell carcinoma of the skin or in situ carcinoma of uterine cervix or ductal\n             carcinoma in situ (DCIS) if properly treated in opinion of the investigator.\n\n          -  Patients who must or wish to continue the intake of restricted medications or any drug\n             considered likely to interfere with the safe conduct of the trial\n\n          -  Previous treatment in this trial\n\n          -  Currently enrolled in another investigational device or drug study, or less than 21\n             days since ending another investigational device or drug study(s), or receiving other\n             investigational treatment(s).\n\n          -  Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,\n             makes them an unreliable study subject or unlikely to complete the trial\n\n          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial.\n             Men who plan to father a child while in the trial.\n\n          -  Prior chemotherapy, biological or radiation therapy, androgens, thalidomide, other\n             anticancer agents, or any investigational drug within 21 days; and/or three half-lives\n             for immunotherapy, before starting any of the trial drugs.\n\n          -  Prior anti CDK (Cyclin-dependent Kinase) agents (except cohort F)\n\n          -  Prior radiotherapy to >= 25% of bone marrow regardless of when it was received\n\n          -  Unresolved treatment related toxicity from previous therapy of > CTCAE grade 1 at\n             study entry (except for stable sensory neuropathy ? CTCAE grade 2 and alopecia)\n\n          -  Previous treatment with IGF (Insulin-like Growth Factor)-1R targeting compounds\n\n          -  Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or\n             leptomeningeal disease, as indicated by clinical symptoms, cerebral oedema, and/or\n             progressive growth. History of CNS metastases or cord compression are eligible if they\n             have been definitively treated (e.g. radiotherapy, stereotactic surgery) and are\n             clinically stable, off anticonvulsants and steroids for at least 4 weeks. Patients\n             with brain metastases are eligible if they are asymptomatic or treated at a stable\n             dose of steroids for at least 4 weeks. Patients are not eligible if they have spinal\n             cord compression.\n\n          -  Any evidence of severe or uncontrolled systemic disease as judged by the Investigator.\n\n          -  Inadequate bone marrow reserve or organ function as demonstrated by any of the\n             following: ANC < 1.5 x 109/L, platelets < 100 x 109/L, haemoglobin <90g/L, ALT > 2.5 x\n             ULN or > 5 x ULN in the presence of liver metastases, total bilirubin >1.5 x ULN or >3\n             x ULN in patients with Gilbert's Syndrome, serum creatinine > 1.5 x ULN concurrent\n             with creatinine clearance <= 50 mL/min.\n\n          -  Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi\n             Syndrome or renal tubular acidosis\n\n          -  Refractory nausea and vomiting, chronic GI diseases, inability to swallow the product,\n             or previous significant bowel resection that would preclude adequate absorption of\n             abemaciclib or resulting in baseline Grade 2 or higher diarrhoea.\n\n          -  History of hypersensitivity to active or inactive excipients of xentuzumab,\n             abemaciclib or letrozole/anastrozole/fulvestrant, or loperamide hydrochloride, or\n             drugs with similar chemical structures\n\n          -  Patients with Diabetes Type I or uncontrolled Type II (defined by HgBA1C > 8%)\n\n          -  Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of\n             life threatening complications in the short term including patients with massive\n             uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and\n             over 50% of liver involvement in metastases.\n\n          -  Prior hematopoietic stem cell or bone marrow transplant\n\n          -  Have a personal history of any of the following conditions: syncope of either\n             unexplained or cardiovascular etiology, ventricular arrhythmia (including but not\n             limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac\n             arrest. Subjects with controlled atrial fibrillation for >30 days prior to study\n             treatment are eligible.\n\n          -  Erythropoietin, G-CSF, and GM-CSF are not allowed within 2 weeks prior to study. The\n             primary prophylactic use of G-CSF is not permitted but it may be used to treat\n             treatment emergent neutropenia.\n\n          -  Have had major surgery (excluding biopsy) < 28 days of the initial dose of any of the\n             study drugs or planned major surgery during study participation.\n\n          -  Have active bacterial, fungal, and/or known viral infection (for example, human\n             immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen, or hepatitis C\n             antibodies). Screening is not required for enrolment.\n\n          -  Patients with baseline Grade >=2 hyperglycaemia or patients with baseline Grade >= 2\n             diarrhoea\n\n          -  Patients needing treatment with CYP3A4 inhibitors/inducers cannot be included in the\n             trial.
Loco-regional treatment within 4 weeks prior to initiation of study treatment.
Prior treatment with a HER3 antibody
Patient is currently receiving treatment with ceritinib within a Novartis-sponsored study which has fulfilled the requirements for the primary objective and, in the opinion of the Investigator, would benefit from continued treatment.
Patient has been permanently and prematurely discontinued from ceritinib study treatment in the parent study due to any reason.
Primary hepatic dysfunction including known cirrhosis or active hepatitis. Patients with biliary obstruction must be stented prior to initiating treatment.
Previous treatment for NHL
Treatment with drugs that have the potential to interfere with metabolism or excretion of mibefradil
Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment
Previous discontinuation of treatment with deferiprone or deferoxamine due to adverse events;
Patients must not be taking Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least two weeks prior to study treatment.
Patient has been permanently discontinued from everolimus study treatment in the parent study.
Patient is receiving everolimus in combination with an unapproved or experimental treatment
Inclusion Criteria:\n\n        -Patient is currently enrolled in a Novartis-sponsored, Oncology Clinical Development &\n        Medical Affairs study receiving nilotinib and has fulfilled all their requirements in the\n        parent study -Patient is currently benefiting from the treatment with nilotinib, as\n        determined by the investigator -Patient has demonstrated compliance, as assessed by the\n        investigator, with the parent study protocol requirements -Willingness and ability to\n        comply with scheduled visits, treatment plans and any other study procedures -Written\n        informed consent obtained prior to enrolling in roll-over study\n\n        Exclusion Criteria:\n\n        - Patient has been permanently discontinued from nilotinib treatment in the parent study\n        due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or\n        any other reason - Patient has participated in a Novartis sponsored combination trial where\n        nilotinib was dispensed in combination with another study medication and patient is still\n        receiving combination therapy -Patients who are currently receiving treatment with any\n        medications that have the potential to prolong the QT interval or inducing Torsade de\n        Pointes and the treatment cannot be either safely discontinued at least one week prior to\n        nilotinib treatment or switched to a different medication prior to start of nilotinib\n        treatment and for the duration of the study -Pregnant or nursing (lactating) women, where\n        pregnancy is defined as the state of a female after conception and until the termination of\n        gestation, confirmed by a positive hcG laboratory test. -Women of child-bearing potential,\n        defined as all women physiologically capable of becoming pregnant, unless they are using\n        highly effective methods of contraception during the study and for 30 days after the final\n        dose of nilotinib.
Prior Temozolomide treatment
Treatment with chronic immunosuppressants
Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Need for other anticancer treatment
Prior treatment with a taxane or other tubulin-targeted agent (eg, indibulin) other than a vinca alkaloid
More than 3 painful lesions or more than 2 requiring immediate localized treatment
Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline
Previous or current treatment with mitotane or other antineoplastic drugs for ACC
Patients who have completed the End of Treatment assessments in their originating study. Every effort should e made to conduct the End of Treatment visit such that the patient does not have any interruption in sorafenib dosing.
Patient on active current treatment of antiplatelet agents (i.e. off-study Aspirin, clopidogrel, ticlopidine)
At study entry, participants must be actively receiving treatment with single-agent PCI-32765 or participants must have participated in a PCI-32765 randomized clinical study in which they initially received comparator treatment and now cross-over to ibrutinib. Note: A minimum of 6 months requirement for prior PCI-32765 treatment will not be mandatory in this case and participants with less than 6 months will be required to have more frequent initial safety assessments
Currently enrolled and receiving treatment in an Incyte-sponsored clinical study of ruxolitinib that has completed or been terminated.
Currently tolerating treatment in the parent protocol.
Has been permanently discontinued from study treatment in the parent study for any reason.
Subjects cannot be simultaneously enrolled on other treatment studies
Current treatment in another clinical study
105 For DLBCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments., with at least one treatment consisting of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP (14 or 21), R-CHOEP, and DA-REOCH. For FL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, R-CVP, and BR. For MCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, BR and hyper-CVAD alternating with R-MTX/Ara-C. For subjects with refractory B-NHL and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks before initiation of study treatment
Previous treatment must include treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent
Previous treatment with CD19-targeted therapy, with the exception of prior lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment
Had prior treatment with napabucasin.
No prior treatment with wee1 kinase inhibition
Must not require concomitant treatment with anticoagulants
3. Morphologically documented relapsed/refractory AML as defined by World Health Organization (WHO) criteria after at least 1 prior therapy for AML with the exception of hydroxyurea, and not felt to have curative treatment options per treating physician, or the patients themselves are unwilling to consider curative treatment options.
Cancer-directed therapy within 2 weeks prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count. Hydroxyurea will be weaned as soon as clinically feasible.
Prior treatment with TAS-102 or regorafenib
Additional Exclusion Criteria for subjects Assigned to Treatment A: Subjects unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
Additional Exclusion Criteria for Subjects Assigned to Treatment B: Unacceptable AEs from previous bortezomib treatment; Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous bortezomib treatment; Intolerance or contraindications to anti-viral prophylaxis.
Prior treatment with sipuleucel-t and Ra-223 is permitted, provided there has been a two-week washout from the last dose
Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-related treatment-emergent adverse events (irTEAEs)
Previous treatment with idelalisib at any time (ZYDELIG®)
Prior treatment with SERMs or SERDs within 5 weeks of first G1T48 dose
Dose level 2 (20 mg) and higher: willing to provide baseline and on treatment tumor biopsies (3 weeks after RXDX-106 treatment initiation), provided the procedure is clinically feasible and not deemed unsafe by the investigator.
Availability of production capacities for the patient's IMA202 product prior to the leukapheresis TREATMENT SCREENING:
Minimum intervals required to be off treatment prior to Cycle 1 Day 1:
No limits to the prior lines of treatment
Predicted time to first treatment of ?3 years according to MDACC nomogram.
Treatment with corticosteroids other than physiological replacement within the previous week or treatment with immunosuppressive medication within the previous week.
Subjects must be primary refractory or relapsed to 1st line intensive treatment for AML or refractory or relapsed after second line of treatment for AML
Previous treatment with crenolanib or prior participation in clinical trial involving crenolanib.
Patients having received prior radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy within the 2 weeks prior to treatment with CPI-613, or those who have not fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment)
Using any systemic treatment for BCC (e.g. vismodegib), or any topical treatment for their BCC tumors, unless discontinued at least one month prior
REGISTRATION TO TREATMENT (STEP 1): No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
REGISTRATION TO TREATMENT (STEP 2): No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
Prior PARP therapy could have been administered as either treatment for recurrent disease or as maintenance following prior treatment.
Patients with prior treatment with idelalisib.
Previous treatment with talimogene laherparepvec or any other oncolytic virus
Sexually active subjects and their partners unwilling to use a male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
Subjects in expansion cohort only: Willing to undergo pre- and on-treatment biopsies
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is > 3 years.
Any other experimental treatment on another clinical trial
Prior treatment with trabectedin or trabectedin analog
Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment
Has had prior treatment with idelalisib
RENAL COHORT: Any number of prior treatment lines is allowed on study
BLADDER: The patient must be systemic treatment naive, previous intra-vesicle therapy is allowed
Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
Previous assignment to treatment during this study; patients permanently withdrawn from study participation will not be allowed to re-enter the study
Prior radiation which overlaps and precludes hypofractionated treatment to the index lesion
Prior treatment with drug targeting cyclin-dependent kinase (CDK) family
All patients must consent to pre-treatment biopsy of the tumor if it can be done safely (as judged by the investigator) during screening. Week 10 on-treatment biopsies will be required for a minimum 10 patients. After 10 paired biopsies have been obtained then week 10 on-treatment biopsy will be made optional.
Patients with spinal cord compression or a history of leptomeningeal carcinomatosis. At the time of day 1 of the study, patients with central nervous system metastases must have been treated and must be asymptomatic and meet the following criteria. 1. No concurrent treatment, inclusive of, but not limited to, surgery, radiation, and/or corticosteroids. (Note: patients are allowed on systemic steroids unless these are being administered to manage central nervous system metastases); 2. Neurologic stability (lack of signs or symptoms greater than baseline prior to radiotherapy) until the time of dosing of MEDI0457; 3. For radiation treatment, patients must be: at least 14 days between last day of stereotactic radiosurgery or gamma-knife treatment and day 1 of protocol treatment, at least 28 days between last day of whole brain radiation therapy and day 1 of protocol treatment, and/or at least 14 days since last dose of corticosteroids and day 1 of protocol treatment.
Patient is on any systemic corticosteroid therapy within one week before the planned date for first dose of treatment or on any other form of immuno-suppressive medication
ENROLLMENT: Patient must have fully recovered (i.e. returned to baseline) from the clinically significant acute treatment-related toxicities of all prior treatments prior to beginning treatment on this protocol with exceptions of cytopenias resulting from persistent disease, hearing loss and alopecia.
Patients receiving any other standard or investigational treatment for their cancer with a primary goal of improving survival within the past 2 weeks prior to initiation of CPI-613 treatment
Prior treatment with docetaxel or cabazitaxel for mCRPC
Prior systemic treatment
Patient is currently receiving medication with a known risk of prolonging the QT interval or inducing torsades de pointes (TdP) and whose treatment cannot be either discontinued or switched to a different medication prior to starting treatment with the study drug.
Patient has received enzalutamide for the treatment of prostate cancer; however, previous treatment with other hormonal therapy (bicalutamide, flutamide, nilutamide, abiraterone and ketoconazole) or chemotherapy (docetaxel, cabazitaxel or mitoxantrone) is allowed
Willingness to undergo fluoroscopy-guided SGB or sham treatment
Any anti-lymphoma treatment within 6 months of treatment initiation.
Previous treatment with cetuximab with evidence of clinical benefit, as defined by complete response, partial response, or prolonged stable disease with 16 or more weeks of treatment without radiographic progression, as assessed by the treating physician and documented in the medical record; this treatment may have occurred at any point in the patient’s clinical course for treatment of metastatic colorectal cancer
Patient who is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
Subjects must agree to undergo two research-directed biopsies during treatment
Started or planning to start on strenuous exercise regimen after first dose of study treatment (i.e., muscular activities, such as strenuous exercise, that can result in significant increase in plasma CK levels should be avoided while on trametinib treatment)
Clinical indication for treatment with azacitidine.
Hydroxyurea within 48 hours prior to first day of study treatment.
Current unstable arrhythmia requiring treatment.
Subjects must have failed prior therapy with abiraterone, enzalutamide, or both: has completed at least 12 weeks of prior continuous therapy with abiraterone or enzalutamide; has not been without abiraterone or enzalutamide treatment for >30 days prior to initiation of study treatment; lead-in dosing period for enzalutamide only will be required under the following circumstance:
Prior treatment: Treated with two or more lines of prior therapy, with disease refractory to both a proteasome inhibitor and an immunomodulatory agent, and disease progression (as defined by International Myeloma Working Group (IMWG) criteria) following treatment with an anti-CD38 monoclonal antibody given as monotherapy or in combination therapy. The most recent treatment regimen must have contained an anti-CD38 monoclonal antibody.
Patient has documented pneumonitis which is active and requiring treatment
Treatment with abiraterone within 2 weeks prior to study treatment
Prior treatment for study indication with:
Prior treatment with CD47 or signal regulatory protein alpha (SIRP?) targeting agents
Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A subject who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If subject is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the subject must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.
Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Subjects who may be receiving leflunomide or letermovir must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Subjects receiving artesunate must discontinue the use prior to the first dose of study treatment.
Subjects who may still be sensitive to repeated treatment with decitabine or azacitidine such as subjects who had response to prior decitabine or azacitidine treatment, but relapsed >6 months after stopping treatment with these agents.
Prior treatment with guadecitabine.
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Subject is ? 18 years of age the time of signing the informed consent form (ICF).\n\n          2. Subject must understand and voluntarily sign an ICF prior to any study-related\n             assessments/procedures being conducted.\n\n          3. Subject is willing and able to adhere to the study visit schedule and other protocol\n             requirements.\n\n          4. Subject has newly diagnosed, primary (ie, de novo) or secondary (progression of MDS or\n             myeloproliferative neoplasms [MPN], or therapy-related) AML according to the WHO\n             classification with ? 20% leukemic blasts in the bone marrow: -Have an Isocitrate\n             dehydrogenase 1 (IDH1) or Isocitrate dehydrogenase 2 (IDH2) gene mutation (R132, R140,\n             or R172)\n\n               -  IDH mutational status will be assessed locally; for sites without local testing\n                  capabilities, a referral lab will be identified.\n\n                    -  By the investigator's assessment who are not candidates to receive intensive\n                       Inductive chemotherapy (IC).\n\n          5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or\n             2.\n\n          6. Subject has adequate organ function defined as:\n\n               -  Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase\n                  (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ? 3 x ULN, unless considered\n                  due to leukemic organ involvement.\n\n               -  Serum total bilirubin < 1.5 x ULN. Higher levels are acceptable if these can be\n                  attributed to ineffective erythropoiesis, 3 times the upper limit of normal for\n                  Gilbert's syndrome (eg, a gene mutation in UGT1A1), or leukemic organ\n                  involvement.\n\n               -  Serum creatinine < 2 x ULN or creatinine clearance > 30 mL/min based on the\n                  Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR):\n\n             GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if\n             African American)\n\n          7. Agree to serial bone marrow aspirate/biopsies.\n\n          8. Females of childbearing potential (FCBP)* may participate, providing they meet the\n             following conditions:\n\n               -  Agree to practice true abstinence ** from sexual intercourse or to use highly\n                  effective contraceptive methods (eg, combined [containing estrogen and\n                  progestogen] or progestogen only associated with inhibition of ovulation, oral,\n                  injectable, intravaginal, patch, or implantable hormonal contraceptive; bilateral\n                  tubal occlusion; intra-uterine device; intrauterine hormone-releasing system; or\n                  male partner sterilization [note that a vasectomized partner is a highly\n                  effective birth control method provided that partner is the sole sexual partner\n                  of the FCBP trial participant and that a vasectomized partner has received\n                  medical assessment of the surgical success]) at screening and throughout the\n                  study, and for at least 4 months following the last study treatment; and\n\n               -  Have a negative serum ?-subunit of human chorionic gonadotropin (?-hCG) pregnancy\n                  test (sensitivity of at least 25 mIU/mL) at screening; and\n\n               -  Have a negative serum or urine (investigator's discretion under local\n                  regulations) ?-hCG pregnancy test (sensitivity of at least 25 mIU/mL) within 72\n                  hours prior to the start of study treatment in the Treatment Period (note that\n                  the screening serum pregnancy test can be used as the test prior to the start of\n                  study treatment in the Treatment Period if it is performed within the 72-hour\n                  timeframe).\n\n          9. Male subjects must agree to practice true abstinence from sexual intercourse or agree\n             to the use of highly effective contraceptive methods (as described above) with\n             non-pregnant female partners of child bearing potential at screening and throughout\n             the course of the study and should avoid conception with their partners during the\n             course of the study and for at least 4 months following the last study treatment (6\n             months following last dose of azacitidine in Canada). Furthermore, the male subject\n             must agree to use a condom while treated with azacitidine and for at least 4 months\n             following the last azacitidine dose.\n\n        Exclusion Criteria:\n\n        - The presence of any of the following will exclude a subject from enrollment:\n\n          1. Subject is suspected or proven to have acute promyelocytic leukemia based on\n             morphology, immunophenotype, molecular assay, or karyotype.\n\n          2. Subject has AML secondary to chronic myelogenous leukemia (CML).\n\n          3. Subject has received a targeted agent against an Isocitrate dehydrogenase 1 (IDH1) or\n             Isocitrate dehydrogenase 2 (IDH2) mutation.\n\n          4. Subject has received prior systemic anticancer therapy, HSCT, or radiotherapy for AML.\n\n             Note: Hydroxyurea is allowed prior to enrollment for the control of peripheral\n             leukemic blasts in subjects with leukocytosis. (however, hydroxyurea should not be\n             given within 72 hours prior to and after administration of azacitidine). For subjects\n             with secondary AML (eg, MDS or MPN) treatment for prior cancer is not exclusionary;\n             full treatment information will be collected within the CRF. The use of all trans\n             retinoic acid (ATRA) for suspected APL is not exclusionary provided it is discontinued\n             prior to initiation of treatment in the protocol.\n\n          5. Subject has received more than 1 cycle of prior treatment with azacitidine, or subject\n             has received any prior treatment with decitabine for Myelodysplastic syndromes (MDS).\n\n             - Clarification: Subjects with newly diagnosed Acute myeloid leukemia (AML) who are\n             currently receiving their 1st cycle of azacitidine (7 days) can be screened for the\n             study. On study, Cycle 1 must be started at 28 days (+/- 3 days) after initiation of\n             the pre-study azacitidine.\n\n          6. Subject has or is suspected of having central nervous system (CNS) leukemia.\n             Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is\n             suspected during screening.\n\n          7. Subject has immediate life-threatening, severe complications of leukemia such as\n             uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated\n             intravascular coagulation.\n\n          8. Subject has significant active cardiac disease within 6 months prior to the start of\n             study treatment, including New York Heart Association (NYHA) class III or IV\n             congestive heart failure; acute coronary syndrome (ACS); and/or stroke; or left\n             ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated\n             acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.\n\n          9. Subject has prior history of malignancy, other than MDS, Myeloproliferative neoplasm\n             (MPN), or AML, unless the subject has been free of the disease for ? 1 year prior to\n             the start of study treatment. However, subjects with the following history/concurrent\n             conditions are allowed:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histologic finding of prostate cancer (T1a or T1b using the tumor,\n                  node, metastasis clinical staging system)\n\n         10. Subject is known seropositive for or has active viral infection with human\n             immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or\n             hepatitis C virus (HCV)\n\n         11. Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other\n             conditions that limit the ingestion or gastrointestinal absorption of drugs\n             administered orally\n\n         12. Subject has uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or\n             diastolic BP > 100 mmHg)\n\n         13. Subject is taking the following sensitive CYP substrate medications that have a narrow\n             therapeutic range are excluded from the study unless the subject can be transferred to\n             other medications at least 5 half-lives prior to the start of study treatment:\n             phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and\n             tizanidine (CYP1A2).\n\n         14. Subject is taking the breast cancer resistance protein (BCRP) transporter-sensitive\n             substrate rosuvastatin; subject should be excluded from the study unless he/she can be\n             transferred to other medications at least 5 half-lives prior to the start of study\n             treatment.\n\n         15. Subject has active uncontrolled systemic fungal, bacterial, or viral infection\n             (defined as ongoing signs/symptoms related to the infection without improvement\n             despite appropriate antibiotics, antiviral therapy, and/or other treatment).\n\n         16. Subject has known or suspected hypersensitivity to any of the components of study\n             therapy.\n\n         17. Subject is taking medications that are known to prolong the QT interval unless he/she\n             can be transferred to other medications within ? 5 half-lives prior to the start of\n             study treatment.\n\n         18. Subject has Heart rate-corrected QT (QTc) interval (ie, Fridericia's correction\n             [QTcF]) ? 450 ms or other factors that increase the risk of QT prolongation or\n             arrhythmic events (eg, heart failure, hypokalemia, family history of long QT interval\n             syndrome) at screening.\n\n         19. Female subject who is pregnant or lactating.\n\n         20. Subject has any significant medical condition, laboratory abnormality, or psychiatric\n             illness that would prevent the subject from participating in the study.\n\n         21. Subject has any condition, including the presence of laboratory abnormalities that\n             places the subject at unacceptable risk if he/she were to participate in the study.\n\n         22. Subject has any condition that confounds the ability to interpret data from the study.
Prior treatment with cabozantinib
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
Presence of biopsiable disease and patient able to undergo pre-treatment and on-treatment biopsy
Have been informed of other treatment options
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
Patients with prior treatment with hypomethylating agents
Previous treatment with talimogene laherparepvec (T-VEC) or any other oncolytic virus
Prior treatment with a CD123xCD3 bispecific agent, T cells expressing CD123 specific chimeric antigen receptor, or toxin-conjugated to CD123 antibodies; prior treatment with naked anti-CD123 monoclonal antibody is permitted
Progression at any time after initiation of azacitidine or decitabine treatment OR
Serum calcium (corrected for albumin) level above the ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment).
TREATMENT: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment; patients with prostate cancer may continue LHRH agonists or antagonists
Subjects must be willing to undergo 2 sets of core needle biopsies (pre-treatment and on-treatment), if there are lesions amenable to biopsy; an optional core biopsy will be requested at progression
Prior systemic therapy directed at advanced RCC is not allowed for patients enrolled to the expansion cohort, treatment naive arm; if prior (neo)adjuvant treatment given as part of a clinical trial, this would be allowed as long as last dose was > 1 year prior to start of treatment
Prior treatment with pomalidomide
Planning to embark on a new strenuous exercise regimen after first dose of study treatment; NOTE: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on binimetinib treatment
Prior treatment with docetaxel.
Previous treatment with TAS-102 or TMZ
Prior treatment with fluoropyrimidines (applicable to Part 1 only)
Subjects for whom a potential 29-day delay in treatment will interfere with the subject’s potential therapeutic options
Previous first line treatment with at least standard dose of radiotherapy (total dose >= 54 Gy) and temozolomide
Has prior treatment with Gliadel unless it was administered as first line treatment and at least 3 months prior to study treatment
Participants are allowed to receive, but are not required to receive, biologic/targeted (noncytotoxic) therapy as part of their primary treatment regimen
Any previous treatment with vosaroxin
Patients that have previously progressed on pomalidomide treatment
Prior treatment, involving interferon, anakinra, imatinib, steroids, chemotherapy with, but not limited to cladribine, vinblastine, 6-mercaptopurine and etoposide, or other medications used empirically for the treatment of ECD, will be acceptable; these therapies should have been completed and discontinued 4 weeks or more prior to enrollment in this study
A treatment regimen containing ibrutinib unless patient is not a candidate
All treatment regimens must have been administered for ?2 cycles unless patient is immediately allergic or intolerant to the regimen
Prior treatment with bevacizumab or other anti-vascular endothelial growth factor (VEGF) drugs
Prior treatment with TPI 287
Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1
No implanted hardware adjacent to the prostate that would prohibit appropriate treatment planning and treatment delivery
The subject has received radiation therapy:\r\n* To the thoracic cavity or gastrointestinal tract within 3 months of the first dose of study treatment\r\n* To bone or brain metastasis within 14 days of the first dose of study treatment\r\n* To any other site(s) within 28 days of the first dose of study treatment
The subject has started treatment with drugs used to control loss of bone mass (eg, bisphosphonates or denosumab) within 4 weeks prior to the first dose of study treatment
Subject has had prior treatment with cabozantinib
Time from last anti-tumor treatment to first radiation treatment at least 1 week
Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 6 weeks prior to first administration of study treatment
Prior treatment with radium-223
Treatment with chronic immunosuppressants
Main Inclusion Criteria:\n\n          1. Histologically or cytologically confirmed adenocarcinoma of the pancreas\n\n          2. Chemo naïve patients with advanced/metastatic disease\n\n          3. Documented decision justifying non eligibility for surgical resection. The\n             documentation of the non eligibility for surgical resection will be reviewed by an\n             independent committee.\n\n          4. Men and women, age >18 years\n\n          5. Men and women of childbearing potential (entering the study after a confirmed\n             menstrual period and who have a negative pregnancy test), must agree to use two\n             methods (one for the patient and one for the partner) of medically acceptable forms\n             of contraception during the study and for 3 months after the last treatment intake.\n\n          6. Patient should be able and willing to comply with study visits and procedures as per\n             protocol.\n\n          7. Patient should understand, sign, and date the written voluntary informed consent form\n             at the screening visit prior to any protocol-specific procedures performed.\n\n        Main Exclusion Criteria:\n\n          1. Patient treated for a cancer other than pancreatic cancer within 5 years before\n             enrollment, with the exception of basal cell carcinoma or in situ cervical cancer\n\n          2. Any condition that the physician judges could be detrimental to subjects\n             participating in this study; including any clinically important deviations from\n             normal clinical laboratory values or concurrent medical events Previous treatment\n\n          3. Any anti-tumor therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or\n             hormonal therapy) within 6 months prior to baseline\n\n          4. Treatment with any investigational agent within 4 weeks prior to baseline
Main Inclusion Criteria:\n\n          1. Histologically or cytologically confirmed adenocarcinoma of the pancreas\n\n          2. Chemo naïve patients with advanced/metastatic disease\n\n          3. Documented decision justifying non eligibility for surgical resection. The\n             documentation of the non eligibility for surgical resection will be reviewed by an\n             independent committee.\n\n          4. Men and women, age >18 years\n\n          5. Men and women of childbearing potential (entering the study after a confirmed\n             menstrual period and who have a negative pregnancy test), must agree to use two\n             methods (one for the patient and one for the partner) of medically acceptable forms\n             of contraception during the study and for 3 months after the last treatment intake.\n\n          6. Patient should be able and willing to comply with study visits and procedures as per\n             protocol.\n\n          7. Patient should understand, sign, and date the written voluntary informed consent form\n             at the screening visit prior to any protocol-specific procedures performed.\n\n        Main Exclusion Criteria:\n\n          1. Patient treated for a cancer other than pancreatic cancer within 5 years before\n             enrollment, with the exception of basal cell carcinoma or in situ cervical cancer\n\n          2. Any condition that the physician judges could be detrimental to subjects\n             participating in this study; including any clinically important deviations from\n             normal clinical laboratory values or concurrent medical events Previous treatment\n\n          3. Any anti-tumor therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or\n             hormonal therapy) within 6 months prior to baseline\n\n          4. Treatment with any investigational agent within 4 weeks prior to baseline
Any of the dosimetric treatment criteria as defined have not been met; patients who become ineligible due to inability to meet dosimetric criteria should not receive treatment as defined in this protocol and will come off the study; any subsequent adjuvant radiation will be delivered at the discretion of the treating physician
Treatment with prohibited medications less than or equal to 14 days prior to\n             treatment with rociletinib
Patients who are currently receiving treatment with any medications that have the\n             potential to prolong the QT interval and the treatment cannot be either discontinued\n             or switched to a different medication before starting rociletinib
Prior treatment with anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) monoclonal antibodies or prior CTLA-4 inhibitor or agonist or prior clusters of differentiation (CD)137 agonist or prior interferon-alfa is not allowed; other forms of prior treatment for melanoma (e.g., aldesleukin [IL-2], anti-tumor vaccine, chemotherapy) are allowed if given before the resection(s) that make(s) the patient eligible for this trial, but these must have been completed at least 4 weeks prior to randomization
Chronic treatment with steroids or any other immunosuppressant drugs
Women who are currently or planning to breastfeed during protocol treatment
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Any line of treatment (first line versus beyond first line)
Prior treatment with 5-fluorouracil, irinotecan or oxaliplatin
Prior treatment with brentuximab vedotin (BV)
HCV treatment experienced or naive\r\n* HCV treatment naive: no prior exposure to any IFN, ribavirin (RBV), or other approved or experimental HCV-specific direct acting antivirals (DAA)\r\n* HCV treatment-experienced: virologic failure after treatment with polyethylene glycol (PEG)- IFN + RBV, NS3 protease inhibitor plus PEG-IFN + RBV, or regimen of sofosbuvir (SOF) +/- RBV +/- PEG-IFN regimen
Any HCV treatment which uses pegylated interferon
HCV genotype 3 treatment experienced with cirrhosis
On a prohibited medication which cannot be stopped during the duration of HCV treatment
Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
Patients may not be on any cytotoxic chemotherapy or hormonal treatment for breast cancer during protocol treatment; (trastuzumab is allowed in HER2 positive patients)
Previous treatment with eribulin mesylate
Prior treatment with docetaxel is allowed but not required
Prior treatment with other second line hormone therapy is allowed (e.g. flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, ARN-509); patients must be off these therapies for at least 4 weeks prior to starting treatment
Prior treatment with Xofigo (223Radium), Provenge, mitoxantrone and cabazitaxel is allowed
Subject is currently receiving treatment with a medication that has a known risk to prolong the QT interval or induce Torsades de Pointes and the treatment cannot be discontinued or switched to a different medication prior to randomization
Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment and remain on treatment until after completion of therapy and until the cluster of differentiation (CD)4 cells are greater than 200/mm^3
All biologic agents including hematopoietic growth factors must have been stopped at least 1 week prior to treatment on the study
Prior treatment with Erwinaze
Prior treatment with any cytotoxic chemotherapy for treatment of pancreatic cancer except as an adjuvant therapy; patient should not have received gemcitabine within 6 months of starting the study treatment; 5-flourouracil or radiation treatment should be received more than 4 weeks prior to receiving the study drug
Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing torsades de pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
Chronic treatment with immunosuppressant drugs
Previous radiotherapy to the lesion(s) of interest, including prior treatment with whole-brain radiation therapy (WBRT); (prior treatment with SRS is allowed if the index lesion[s] is in a different, non-contiguous location than the previously treated lesion)
Prior treatment with dasatinib, imatinib or nilotinib
PROCEEDING TO TREATMENT WITH 5-FC:
Urgent need of treatment to prevent acute neurologic deterioration
Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up
Have previously completed or withdrawn from this study or any other study investigating dasatinib; prior treatment with other tyrosine kinases, including afatinib, is acceptable
Patient must have been eligible for and initially randomized to Arm 1 (low dose carfilzomib), begun cycle 2 of treatment, and progressed prior to completing 12 cycles of protocol therapy
Concurrent chemotherapy (except hydroxyurea) or interleukin-2 (IL-2) therapy or anticipated need during the study treatment for 1 week after the last dose of ALT-803-hydroxyurea is permitted at any time to control blast count
No prior radionuclide treatment within 6 weeks of the first dose of study treatment
No hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 12 weeks before the first dose of study treatment
Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vemurafenib, breastfeeding must be discontinued prior to treatment day 1 of the study
No radiotherapy, treatment with cytotoxic agents (except CPI-613), treatment with biologic agents or any anti-cancer therapy within the 2 weeks prior to treatment with CPI-613; hydroxyurea and oral tyrosine kinase inhibitors being used without grade =< 2 toxicity can be taken until day 1 of therapy; patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, non-hematologic, non-infectious toxicities from prior treatment =< grade 2 are eligible, but must be documented as such
At screening, patients may be included if the largest lesion is > 1 cm or > 3 in number, if the patient has underdone treatment with surgery and/or radiation therapy and there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment
Prior treatment with trastuzumab
Current treatment or treatment within 4 weeks of screening with bisphosphonates.
History of prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) blocking antibody
Subjects with an indication for AHCT for the treatment of PCM as determined by the principal investigator (PI) or lead associate investigator (LAI)\r\n* Subjects following induction treatment for PCM\r\n* Subjects with recurrent or persistent evaluable disease who have not undergone AHCT for the treatment of the PCM
Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria
Current treatment on another clinical trial; participation in non-therapeutic clinical trials is permissible
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Patients who have relapsed from their initial doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) or similar standard treatment regimen and have not received any other chemotherapy or salvage systemic treatment
Patients must have had prior treatment with bilateral orchiectomy or androgen\n             deprivation therapy with an LHRH-blocker with evidence of treatment failure
Patients must have a Karnofsky performance status (KPS) rating of >= 60 prior to initiating treatment; patients may be enrolled at a KPS of < 60 if it is felt that the patient will have adequate opportunity to recover to a KPS >= 60 by the initiation of treatment
AT TIME OF TREATMENT:
AT TIME OF TREATMENT:
No prior treatment with LMB-2
Prior treatment with IMGN853
Prior treatment with adenovirus-based drugs
Patients with recurrent disease may have received prior treatment with carboplatin/paclitaxel but must have had a treatment free interval of > 6 months
Subject agrees not to participate in another interventional study while on treatment.
Use of T cell depleting agents for prevention or treatment of rejection at any point prior to or after enrollment in the study
Is ineligible or inappropriate for other treatment regimens known to have effective potential
Systemic strontium-89, samarium-153, rhenium-186, or rhenium-188 for bone metastases within 24 weeks prior to initiation of study treatment
Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for cytotoxic agents, or for at least 5 half-lives for non cytotoxic agents.
Prior treatment with quizartinib or participated in a prior quizartinib study.
Prior systemic treatment in the metastatic setting with Vascular epithelial growth factor(VEGF) or VEGF receptor targeted therapy
Prior treatment with imetelstat
Prior treatment with eribulin
Participants with chronic infection by Hepatitis C Virus (HCV) who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, participants with successful HCV treatment are allowed as long as there are >4 weeks between achieving sustained viral response (SVR12) and start of study drug.
Prior treatment with CD19 directed agents unless CD19 expression is confirmed after completion of CD19-directed treatment
Patient is to receive bevacizumab as maintenance treatment
High-grade Ta papillary disease based on a biopsy within 8 weeks of the initial dose of study treatment. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy to the initial dose of study treatment must be within 8 weeks. This diagnosis must be confirmed by the independent central pathology reviewer prior to subject enrollment. A subject with persistent T1 disease on the second (i.e., restaging) TURBT may be enrolled in this study only if the investigator documents the subject declines cystectomy.
History of recurrent severe urinary tract infections (UTIs) per investigator judgment. Subjects with a current UTI requiring antibiotic treatment may defer the initiation of Vicinium treatment on Day 1 until resolution of the UTI (even if this extends the screening period requirements to start of Vicinium treatment).
Treatment with immunotherapy against PCa within the previous 6 months prior to randomization
Radiographic evidence of recurrent NSCLC prior to afatinib treatment
Receipt of any experimental treatment within 30 days of start of treatment with afatinib until the end of treatment visit
For Cohort A: Has received docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC is allowed. Up to 2 second-generation hormonal manipulations (e.g., abiraterone acetate and/or enzalutamide) are allowed
For Cohort B: Has received prior treatment with either abiraterone acetate or enzalutamide (but not both) in the prechemotherapy mCRPC state. Participants in Cohort B must have received at least 4 weeks of either abiraterone or enzalutamide treatment (but not both) who failed treatment or became intolerant of the drug
For Cohort C: Has received prior treatment with abiraterone acetate in the pre-chemotherapy mCRPC state without prior enzalutamide. Participants in Cohort C must have received at least 4 weeks of abiraterone treatment who failed treatment or become intolerant of the drug.
Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening
They have other medical problems that could get much worse with this treatment.
Participant treated with any prior systemic therapy with the exception of the following:\r\n* Treatment by localized radiotherapy for a specific indication within 2 weeks of initiation of treatment\r\n* Treatment with corticosteroids, not to exceed the equivalent of 160 mg of dexamethasone over a four-week period before initiation of protocol therapy
Any prior treatment with dalantercept or any other agent targeting ALK1 pathway.
Any prior treatment with axitinib.
Patient who have had previous treatment with pazopanib or with weekly gemcitabine for recurrent or persistent disease
Patients with prior trastuzumab treatment
All other significant diseases might impair the subject's tolerance of trial treatment
Patients with gliomas who have had prior treatment with bevacizumab (Avastin) are excluded
Prior treatment with gene therapy product
CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate) f. Radiotherapy:
Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
Prior cabozantinib treatment.
If the subject has DLBCL, there is no curative option with conventional therapy and the prior treatment included ? 1 prior combination chemoimmunotherapy regimen.
If the subject has RS, the subject must have had ?1 prior treatment with a combination chemoimmunotherapy regimen.
Must have failed last line of treatment (refractory to last line of treatment).
Inclusion Criteria:\n\n        Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Subject is ? 18 years of age the time of signing the informed consent form (ICF).\n\n          2. Documented diagnosis of MDS according to World Health Organization (WHO)/French\n             American British (FAB) classification that meets IPSS R classification of very low,\n             low, or intermediate risk disease, and:\n\n        Ring sideroblast ? 15% of erythroid precursors in bone marrow or ? 5% (but < 15%) if SF3B1\n        mutation is present.\n\n          -  < 5% blasts in bone marrow\n\n          -  Peripheral blood WBC count < 13,000/µL 3. Requires red blood cell RBC transfusions 4.\n             Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 5. Subjects who are\n             refractory/intolerant/ineligible to prior ESA treatment, defined as:\n\n          -  Refractory to prior Erythropoiesis- stimulating agents(ESA) treatment: documentation\n             of non-response or response that is no longer maintained to prior ESA-containing\n             regimen, either as single agent or combination (eg, with G-CSF); ESA regimen must have\n             been either recombinant human erythropoietin (rHu EPO) ? 40,000 IU/wk for at least 8\n             doses or equivalent OR darbepoetin alpha ? 500 ?g Q3W for at least 4 doses or\n             equivalent\n\n          -  Intolerant to prior ESA treatment: documentation of discontinuation of prior\n             ESA-containing regimen, either as single agent or combination (eg, with G-CSF), at any\n             time after introduction due to intolerance or an adverse event\n\n          -  ESA ineligible: low chance of response to ESA base on endogenous serum erythropoietin\n             level > 200 U/L for subjects not previously treated with ESAs\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from enrollment:\n\n          1. Prior therapy with disease modifying agents for underlying MDS disease.\n\n          2. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)\n\n          3. MDS associated with del 5q cytogenetic abnormality\n\n          4. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury\n             or treatment with chemotherapy and/or radiation for other diseases.\n\n          5. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies,\n             or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding\n\n             - iron deficiency to be determined by serum ferritin less than or equal to 15 ug/L and\n             additional testing if clinically indicated (eg, calculated transferrin saturation\n             [iron/total iron binding capacity less than or equal to 20%] or bone marrow aspirate\n             stain for iron).\n\n          6. Prior allogeneic or autologous stem cell transplant\n\n          7. Known history of diagnosis of Acute myeloid leukemia (AML)\n\n          8. Use of any of the following within 5 weeks prior to randomization:\n\n               -  anticancer cytotoxic chemotherapeutic agent or treatment\n\n               -  corticosteroid, except for subjects on a stable or decreasing dose for ? 1 week\n                  prior to randomization for medical conditions other than MDS\n\n               -  iron-chelating agents, except for subjects on a stable or decreasing dose for at\n                  least 8 weeks prior to randomization\n\n               -  other RBC hematopoietic growth factors (eg, Interleukin-3)\n\n               -  investigational drug or device, or approved therapy for investigational use. If\n                  the half-life of the previous investigational product is known, use within 5\n                  times the half-life prior to randomization or within 5 weeks, whichever is longer\n                  is excluded.\n\n          9. Prior history of malignancies, other than MDS, unless the subject has been free of the\n             disease (including completion of any active or adjuvant treatment for prior\n             malignancy) for ? 5 years. However, subjects with the following history/concurrent\n             conditions are allowed:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix\n\n               -  Carcinoma in situ of the breast\n\n               -  Incidental histologic finding of prostate cancer (T1a or T1b using the tumor,\n                  nodes, metastasis [TNM] clinical staging system)\n\n         10. Major surgery within 8 weeks prior to randomization. Subjects must have completely\n             recovered from any previous surgery prior to randomization
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)
Treatment with any prior gene therapy product
Prior treatment with any adoptive T cell therapy
For RCC, prior treatment with everolimus or temsirolimus
For gastric or GEJ adenocarcinoma, prior treatment with any taxane
For CRC, prior treatment with cetuximab or panitumumab
Patients must have marrow function and organ function as defined below\r\n* Note: to remain on treatment, any abnormal lab values allowed by the PI must remain stable or improve during treatment; similar off treatment rules will be applied to all patients, except the following: the grade of any abnormal laboratory (lab) value allowed by the protocol principal investigator (P.I.) at enrollment will be considered the patient’s baseline for potentially resuming therapy after modification/holding of therapy when off treatment criteria are applied
Inclusion:\n\n          1. Male or female 1 to 21 years of age at the time of consent\n\n          2. Steroid-refractory grade B-D aGvHD.\n\n               -  Steroid-refractory is defined as a failure to respond to steroid treatment, with\n                  failure to respond defined as any grade B-D (IBMTR grading) aGvHD that shows\n                  progression ? 3 days, or no improvement by 5 days of treatment with 12 mg/kg/day\n                  methylprednisolone or equivalent in subjects with lower GI or liver disease, or\n                  skin disease associated with bullae. Grade D organ involvement will be limited to\n                  skin and liver.\n\n               -  Steroid refractory may also be defined as a failure to respond to 1 mg/kg/day of\n                  methylprednisolone or equivalent in subjects with disease confined to upper GI\n                  disease or lesser degrees of skin GvHD.\n\n               -  Subjects with lack of complete response after 2 weeks of steroid treatment.\n\n          3. A Lansky scale Performance Status score ? 30.\n\n          4. Laboratory values are within the following limits, assessed within 3 days of the first\n             study treatment:\n\n               -  Absolute neutrophil count > 0.5 × 10^9/L.\n\n               -  Creatinine level < 2 times the upper limit of normal.\n\n          5. For patients with isolated upper GI symptoms, pre-Screening biopsy results to confirm\n             diagnosis of aGvHD.\n\n          6. Female patients of childbearing potential and nonsterilized males who are sexually\n             active with a female partner must be practicing highly effective, reliable, and\n             medically approved contraceptive regimen throughout their participation in the study\n             and for 3 months following the last ECP treatment. Or, for the US only, abstinence may\n             be used in place of an approved contraceptive regimen. Females of childbearing\n             potential are those who have reached the onset of menarche, or 8 years of age,\n             whichever comes first. Approved contraceptive methods for female patients of\n             childbearing potential or nonsterilized males who are sexually active with a female\n             partner are as follows:\n\n               -  Barrier methods of contraception: condom or occlusive cap (diaphragm or\n                  cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.\n\n               -  Established use of oral, injectable, or implanted hormonal methods of\n                  contraception.\n\n               -  Placement of an intrauterine device or intrauterine system.\n\n          7. Signed informed consent/assent is obtained before conducting any study procedures; the\n             parent, legal guardian, or legally authorized representative of a minor must also\n             provide written informed consent.\n\n        Exclusion:\n\n          1. Currently enrolled in another clinical trial for the treatment of aGvHD.\n\n          2. Use of any experimental regimens or medication(s) for aGvHD treatment.\n\n          3. Treatment with > 2.0 mg/kg/day of methylprednisolone equivalents for aGvHD within 30\n             days prior to the first study treatment.\n\n          4. Overt signs of relapse of the underlying condition.\n\n          5. Uncontrolled viral, fungal, or bacterial infection.\n\n          6. Platelet count < 20.0 × 10^9/L, despite platelet transfusion.\n\n          7. Inability to tolerate the extracorporeal volume shifts associated with ECP treatment.\n\n          8. Uncontrolled GI bleeding.\n\n          9. Veno-occlusive liver disease.\n\n         10. Life expectancy < 4 weeks.\n\n         11. Patient requires invasive ventilation or vasopressor support.\n\n         12. Known human immunodeficiency virus (HIV) or hepatitis B or C virus infection (proof of\n             seronegativity within 6 months of screening is required).\n\n         13. Known allergy or hypersensitivity to methoxsalen, Uvadex, or its excipients.\n\n         14. Known hypersensitivity and allergy to heparin and Anticoagulant Citrate Dextrose\n             Formula-A (ACD-A).\n\n         15. Co-existing photosensitive disease (e.g., porphyria, systemic lupus erythematosus,\n             albinism) or aphakia.\n\n         16. Coagulation disorders that cannot be corrected with simple transfusion.\n\n         17. Co-existing melanoma, basal cell, or squamous cell skin carcinoma.\n\n         18. Previous splenectomy.\n\n         19. White blood cell count greater than 25,000 mm3.\n\n         20. Currently being treated with any systemic immunosuppressive or biologic therapy for\n             the treatment of a medical condition other than aGvHD.\n\n         21. Female patient is breastfeeding or pregnant.\n\n         22. Any medical concerns that may pose risk to the patient.\n\n         23. Any psychological, familial, sociological, and/or geographical condition that may\n             potentially hamper compliance with the study protocol and follow-up schedule.
Concurrent treatment with any medical that prolongs QT interval and may induce torsades de pointes, and which cannot be discontinued at least 2 weeks before treatment with ASTX660. [Applies to Phase 1 only].
Hydroxyurea will not be considered a prior line of treatment.
Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., inversion 16, t(16;16), t(8;21), t(15;17)).
Hydroxyurea will not be considered a prior line of treatment.
Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., inversion 16, t(16;16), t(8;21), t(15;17)).
Histologically and/or cytologically confirmed and radiographically measurable KRAS and NRAS wild-type adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable; subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan and bevacizumab or have contraindication to such treatment; in addition, for the monotherapy MET Amplified cohort, subjects must have received prior treatment with anti-EGFR therapy (either panitumumab or cetuximab)
For Combination Expansion cohort only: prior treatment with cetuximab or panitumumab
Radionuclide treatment, including yttrium-90 treatment, within 6 weeks of the first dose of study treatment
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
Planned treatment with biological agents within 28 days prior to receiving TheraSphere (may resume after Y-90 treatment or immediately if in control arm)
Toxicities due to prior cancer therapy that have not resolved before the initiation of study treatment, if the Investigator determines that the continuing complication will compromise the safe treatment of the patient
Treatment with chemotherapy less than or equal to (</=) 3 weeks before study treatment
Treatment with biologic therapy </= 3 weeks before study treatment
Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), are allowed
Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances
Must have received at least 2 prior lines of therapy for the treatment of current histology; there are no treatment options available known to provide clinical benefit. Refer to National Comprehensive Cancer Network (NCCN) guidelines of each respective histology for guidance.
For the most recently received VEGFR-targeting TKI there must have been progression of disease as determined by the treating physician either (i) during treatment or (ii) within 6 mo following completion of at least 4 weeks of treatment with the TKI
Recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator.
Prior treatment with TRC105
Current treatment on another therapeutic clinical trial
History of peptic ulcer within the past 3 months of treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
Prior treatment:\r\n* No radiotherapy within 90 days prior to pre-registration\r\n* No prior treatment with any anti-angiogenic agent targeting the vascular endothelial growth factor (VEGF) pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept or sorafenib\r\n* No prior treatment with HSPPC-96 or other investigational immunotherapy\r\n* Must have received prior treatment with radiotherapy and temozolomide for histologically confirmed GBM at initial diagnosis\r\n* No tumor directed therapy for most recent progression\r\n* No prior Gliadel wafers
Prior treatment with prolifeprospan 20 with carmustine wafer.
Patients must not have received any treatment after discontinuing MEDI4736 with the following exceptions; localized palliative radiation therapy is allowed for symptom management, provided and treatment is completed >= 14 days prior to RE-TREATMENT registration; local treatment for brain metastases is allowed
Have two negative pregnancy tests as verified by the investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence2 from heterosexual contact.
Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid (ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of Cycle 1 Day 1), for Cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed)
Willingness to provide pretreatment and on-treatment biopsies.
Treatment with any prior gene therapy product
For treatment-naïve subjects only:
Systemic treatment with anticancer therapy within 3 weeks before study drug treatment
Patients must have disease amenable to biopsy and must be willing to undergo a paired biopsy for correlative analyses (the first biopsy within 28 days prior to start of treatment and the second biopsy while on treatment)
Prior treatment with entrectinib.
Prior treatment for lymphoid malignancy requiring treatment for progressive disease
Ongoing medically significant adverse events from previous treatment, regardless of the time period
Prior treatment with PM01183 or trabectedin.
Post resection serum cancer antigen (CA)19-9 =< 180 units/mL AND prior to any systemic treatment
Patients who are already on prescribed treatment for paronychia who are not willing to discontinue this treatment and only use study drug (no washout period required)
Ineligible for intensification treatment due to age or significant comorbidity
Refused intensification treatment and/or ASCT
Discontinued all prior treatment for cancer at least 14 days prior to initial dose of study treatment.
Previous cytotoxic, cytostatic, hormonal, biological or immunological treatment (ESA with or without G-CSF and iron chelating therapy and hydroxyurea are allowed under certain conditions, see exclusion criterion #5) or biologic treatment for AML.
Previous treatment with ibrutinib
Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for the treatment of prostate cancer or participation in a clinical study of an investigational agent that inhibits the AR or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).
Relapsed and refractory patients must have achieved at least a partial response to previous treatment with proteosome inhibitor or lenalidomide, or both, but progressed within 6 months, and were refractory to their last treatment
Prior treatment with pomalidomide
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy
Must have failed last line of treatment (refractory to last line of treatment).
Refractory to or relapsed after at least 1 prior treatment line.
Current treatment with therapeutic anticoagulants
Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment
Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
Follicular low-grade NHL: either treatment naïve (except for France) or relapsed or refractory following at least one prior treatment. In Part 1 Dose Escalation only, in addition to follicular NHL, marginal zone B cell lymphomas: either treatment naïve or relapsed or refractory following at least one prior treatment.
Inclusion Criteria:\n\n          -  Definitive diagnosis of unresectable locally advanced or metastatic RCC with\n             clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior\n             treatment in the metastatic setting\n\n          -  Evaluable Memorial Sloan Kettering Cancer Center risk score\n\n          -  Measurable disease, as defined by RECIST v1.1\n\n          -  Karnofsky performance status greater than or equal to 70%\n\n          -  Adequate hematologic and end-organ function prior to randomization\n\n        Exclusion Criteria:\n\n        Disease-Specific Exclusions:\n\n          -  Radiotherapy for RCC within 14 days prior to treatment\n\n          -  Active central nervous system disease\n\n          -  Uncontrolled pleural effusion, pericardial effusion, or ascites\n\n          -  Uncontrolled hypercalcemia\n\n          -  Any other malignancies within 5 years except for low-risk prostate cancer or those\n             with negligible risk of metastasis or death\n\n        General Medical Exclusions:\n\n          -  Life expectancy less than 12 weeks\n\n          -  Participation in another experimental drug study within 4 weeks prior to treatment\n\n          -  Pregnant or lactating women\n\n          -  Known hypersensitivity to any component of atezolizumab or other study medication\n\n          -  History of autoimmune disease except controlled, treated hypothyroidism or type I\n             diabetes mellitus\n\n          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced\n             pneumonitis, or idiopathic pneumonitis\n\n          -  Positive human immunodeficiency virus test\n\n          -  Active or chronic hepatitis B or C\n\n          -  Severe infections within 4 weeks prior to treatment\n\n          -  Exposure to oral or IV antibiotics within 2 weeks prior to treatment\n\n          -  Live attenuated vaccines within 4 weeks prior to treatment, 28 days prior to\n             randomization, during treatment, or within 5 months following last dose of\n             atezolizumab\n\n          -  Significant cardiovascular disease\n\n          -  Prior allogeneic stem cell or solid organ transplantation\n\n        Exclusion Criteria Related to Medications:\n\n          -  Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic\n             T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1\n             therapeutic antibody or pathway-targeting agents\n\n          -  Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or\n             immunosuppressive agents within 2 weeks prior to treatment\n\n        Bevacizumab- and Sunitinib-Specific Exclusions:\n\n          -  History of hypertensive crisis or hypertensive encephalopathy\n\n          -  Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds
Adults with ALL in need of treatment
Prior treatment with nintedanib
Prior treatment with regorafenib
No prior treatment with GDC-0810 (allowed only during dose expansion stage)
Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.
Inclusion Criteria:\n\n          -  Histologically or cytologically documented locally advanced or metastatic solid tumors\n             meeting the following study drug-specific criteria:\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1\n\n          -  Life expectancy greater than or equal to (>/=) 12 weeks\n\n          -  Measurable disease, as defined by RECIST v1.1\n\n          -  Adequate hematologic and end organ function as confirmed by laboratory results within\n             14 days prior to the first study treatment\n\n        Inclusion criteria specific to Arm A: Atezolizumab+ Ipilimumab\n\n          -  Escalation stage: NSCLC participants\n\n          -  Mandatory biopsy cohort: NSCLC or melanoma atezolizumab\n\n          -  Prior atezolizumab-treated cohort: participants with NSCLC or melanoma previously\n             treated with atezolizumab\n\n        Inclusion criteria specific to Arm B: Atezolizumab+ Interferon alfa-2b\n\n          -  Escalation stage: RCC or melanoma participants\n\n          -  Expansion stage: RCC or melanoma participants\n\n          -  Mandatory biopsy cohort: RCC or melanoma participants\n\n          -  Prior immunotherapy-treated cohort: participants with RCC, NSCLC, or melanoma\n             previously treated with programmed death-ligand 1 (PD-L1)/ Programmed death 1 (PD-1)\n\n        Inclusion Criteria Specific to Arm C (Atezolizumab plus PEG-Interferon Alafa-2a):\n\n          -  Cohort 1: participants with RCC\n\n          -  Cohort 2: participants who were previously treated with anti-PD-L1/PD-1 with locally\n             advanced or metastatic solid tumor (e.g., NSCLC, RCC, or melanoma)\n\n        Inclusion Criteria Specific to Arm D (Atezolizumab plus PEG?Interferon Alfa-2a\n        +Bevacizumab)\n\n          -  Cohort 1: participants with metastatic RCC with no prior line of systemic therapy for\n             metastatic disease\n\n          -  Cohorts 2-3: disease progression during or after at least one previous systemic,\n             anti-cancer treatment for locally advanced or metastatic solid tumors; participants\n             with sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic\n             lymphoma kinase (ALK) rearrangements must have failed or are intolerant to prior\n             treatment with EGFR or ALK inhibitors; participants with melanoma with actionable BRAF\n             mutations (e.g., V600) must have failed or are intolerant to prior treatment with BRAF\n             inhibitors\n\n        Inclusion Criteria Specific to Arm E (Atezolizumab +Obinutuzumab)\n\n        - R/M HNSCC participants with at least one prior line of systemic therapy\n\n        Inclusion Criteria Specific to prior Anti?PD-L1/PD-1 Treated Cohorts:\n\n          -  No permanent discontinuation of atezolizumab or other immunotherapies due to a\n             treatment-related adverse event\n\n          -  Recovery from all immunotherapy-related adverse events to Grade less than or equal to\n             (?) 1 or baseline at the time of consent\n\n        Exclusion Criteria:\n\n        General Medical Exclusions:\n\n          -  Pregnant and lactating women\n\n          -  Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3\n             weeks prior to initiation of study treatment, with the following exception: (1)\n             hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors\n             (TKIs) that have been discontinued greater than (>) 7 days prior to Cycle 1, Day 1,\n             baseline scans must be obtained after discontinuation of prior TKIs\n\n          -  Investigational therapy within 28 days prior to initiation of study treatment\n\n          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to\n             chimeric or humanized antibodies or fusion proteins\n\n          -  Known hypersensitivity or allergy to Chinese hamster ovary cell products or any\n             component of the atezolizumab formulation\n\n          -  History of or active autoimmune disease\n\n          -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced\n             pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active\n             pneumonitis on screening chest computed tomography (CT) scan\n\n          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation\n\n          -  History of human immunodeficiency virus (HIV)\n\n          -  Participants with active hepatitis B\n\n          -  Participants with active hepatitis C\n\n          -  Participants with active tuberculosis\n\n          -  Participants with a history of confirmed progressive multifocal leukoencephalopathy\n\n          -  Any serious medical condition, physical examination finding, or abnormality in\n             clinical laboratory tests that, in the investigator's judgment, precludes the\n             participant's safe participation in and completion of the study\n\n        Cancer-Specific Exclusions:\n\n          -  Active or untreated central nervous system (CNS) metastases, as determined by CT or\n             magnetic resonance imaging (MRI) evaluation during screening and prior radiographic\n             assessments\n\n          -  Spinal cord compression not definitively treated with surgery and/or radiation or\n             previously diagnosed and treated spinal cord compression without evidence that disease\n             has been clinically stable for >/= 2 weeks prior to screening\n\n          -  Leptomeningeal disease\n\n          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent\n             drainage procedures (once monthly or more frequently); participants with indwelling\n             catheters are allowed.\n\n          -  Uncontrolled tumor-related pain\n\n          -  Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of\n             bisphosphonate therapy or denosumab\n\n          -  History of other malignancy within 2 years prior to screening, except for\n             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,\n             Stage I uterine cancer, localized prostate cancer treated with curative intent, ductal\n             carcinoma in situ treated surgically with curative intent, or other cancers with a\n             similar outcome\n\n        Exclusion Criteria Related to Medications:\n\n          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune\n             checkpoint blockade therapies (Note: Participants enrolled in the prior\n             anti?PD-L1/PD-1 treated cohorts with melanoma may have received prior anti-cytotoxic\n             T-lymphocyte-associated protein 4 treatment or other immunotherapies)\n\n          -  Treatment with systemic immunostimulatory agents within four weeks or five half-lives\n             of the drug, whichever is shorter, prior to Cycle 1, Day 1\n\n          -  Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1,\n             Day 1 (the use of inhaled corticosteroids and mineralocorticoids is allowed)\n\n        Exclusion Criteria Specific to Interferon Alpha Therapy (Arms B?D):\n\n          -  History of depression, suicidal ideation or behavior, bipolar disorder, or psychosis\n\n          -  Hypersensitivity to interferon alpha or any component of the product\n\n        Exclusion Criteria Specific to Bevacizumab (Arm D)\n\n          -  Inadequately controlled hypertension\n\n          -  Prior history of hypertensive crisis or hypertensive encephalopathy\n\n          -  Significant vascular disease within 6 months prior to Day 1\n\n          -  History of hemoptysis\n\n          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of\n             therapeutic anticoagulation)\n\n          -  History of tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal\n             abscess within 6 months prior to Day 1\n\n          -  Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine\n             parenteral hydration, parenteral nutrition, or tube feeding\n\n          -  Evidence of abdominal free air that is not explained by paracentesis or recent\n             surgical procedure\n\n          -  Proteinuria, as demonstrated by urine dipstick or > 1.0 gram of protein in a 24-hour\n             urine collection\n\n          -  Metastatic disease that involves major airways or blood vessels, or centrally located\n             mediastinal tumor masses of large volume\n\n        Exclusion Criteria Specific Obinutuzumab (Arm E)\n\n          -  Hypersensitivity to obinutuzumab\n\n          -  Prior treatment with obinutuzumab
Inclusion Criteria:\n\n        - Subjects must satisfy the following criteria to be enrolled in the study:\n\n          1. Adults (age ? 18 years at the time of signing the ICD) with documented diagnosis of MM\n             and measurable disease (serum M-protein ? 0.5 g/dL or urine M-protein ? 200 mg/24\n             hours).\n\n          2. Subjects enrolling in Cohort A (Pom+LD-dex) must have received 2 prior treatment lines\n             of anti-myeloma therapy. Subjects enrolling in Cohort B (Pom+Dara+LD-dex) must have\n             received 1 or 2 prior treatment lines of anti-myeloma therapy.\n\n          3. All subjects must have received prior treatment with LEN or a LEN-containing regimen\n             for at least 2 consecutive cycles as the most recent treatment regimen.\n\n          4. All subjects must have documented disease progression during or after their last\n             antimyeloma therapy.\n\n          5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status\n             score of 0, 1, or 2.\n\n          6. Subjects must understand and voluntarily sign an ICD prior to any study related\n             assessments/procedures being conducted.\n\n          7. Subjects must be able to adhere to the study visit schedule and other protocol\n             requirements.\n\n          8. All subjects must provide an adequate bone marrow sample at screening that\n             definitively evaluates the presence or absence of myelodysplastic changes.\n\n          9. Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of\n             contraception* simultaneously or practice complete abstinence from heterosexual\n             contact for at least 28 days before starting study drug, while participating in the\n             study (including during dose interruptions), and for at least 28 days after study\n             treatment discontinuation and must agree to regular pregnancy testing during this\n             timeframe. For subjects enrolled in Cohort B, pregnancy prevention and testing will\n             continue until 3 months after last dose of daratumumab.\n\n         10. Females must agree to abstain from breastfeeding during study participation and 28\n             days after study drug discontinuation. Female subjects enrolled in Cohort B must agree\n             to abstain from breastfeeding and donating eggs during study participation and until 3\n             months after last dose of daratumumab.\n\n         11. Males must agree to use a latex condom during any sexual contact with FCBP while\n             participating in the study and for 28 days following discontinuation from this study,\n             even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B\n             must agree to use a latex condom during any sexual contact with FCBP while\n             participating in the study and until 3 months after last dose of daratumumab.\n\n         12. Males must also agree to refrain from donating semen or sperm during the treatment\n             phase and for 28 days after discontinuation from this study treatment. Male subjects\n             enrolled in Cohort B must also agree to refrain from donating semen or sperm during\n             the treatment phase and until 3 months after last dose of daratumumab.\n\n         13. All subjects must agree to refrain from donating blood while on study therapy and for\n             28 days after discontinuation from this study treatment.\n\n         14. All subjects must agree not to share medication.\n\n        Exclusion Criteria:\n\n        The presence of any of the following will exclude a subject from study enrollment:\n\n          1. Any of the following laboratory abnormalities:\n\n               -  Absolute neutrophil count < 1,000/?L\n\n               -  Platelet count < 75,000/?L for subjects in whom < 50% of bone marrow nucleated\n                  cells are plasma cells; or a platelet count < 30,000/?L for subjects in whom ?\n                  50% of bone marrow nucleated cells are plasma cells.\n\n               -  Severe renal impairment (Creatinine Clearance [CrCl] < 30 mL/min) requiring\n                  dialysis.\n\n               -  Corrected serum calcium > 11.5 mg/dL (> 2.8 mmol/L)\n\n               -  Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or\n                  recombinant human erythropoietin use is permitted)\n\n               -  Serum SGOT/AST or SGPT/ALT > 3.0 x the upper limit of normal (ULN)\n\n               -  Serum total bilirubin > 2.0 mg/dL (34.2 ?mol/L); or > 3.0 x ULN for subjects with\n                  hereditary benign hyperbilirubinemia\n\n          2. Prior history of malignancies, other than MM, unless the subject has been free of the\n             disease for ? 5 years. Allowed exceptions include the following:\n\n               -  Basal or squamous cell carcinoma of the skin\n\n               -  Carcinoma in situ of the cervix or breast\n\n               -  Incidental histological finding of prostate cancer (TNM [tumor, nodes,\n                  metastasis] stage of T1a or T1b)\n\n          3. Previous therapy with pomalidomide or daratumumab\n\n          4. Hypersensitivity to thalidomide, LEN, or dex (this includes ? Grade 3 rash during\n             prior thalidomide or LEN therapy)\n\n          5. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem\n             cell transplant less than 12 months prior to initiation of study treatment and who\n             have not discontinued immunosuppressive treatment for at least 4 weeks prior to\n             initiation of study treatment and are currently dependent on such treatment.\n\n          6. Subjects with any one of the following:\n\n               -  Congestive heart failure (NY Heart Association Class III or IV)\n\n               -  Myocardial infarction within 12 months prior to starting study treatment\n\n               -  Unstable or poorly controlled angina pectoris, including Prinzmetal's variant\n                  angina pectoris\n\n          7. Subjects who received any of the following within 14 days of initiation of study\n             treatment:\n\n               -  Major surgery (kyphoplasty is not considered major surgery)\n\n               -  Use of any anti-myeloma drug therapy\n\n          8. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer)\n             of treatment, unless approved by the sponsor.\n\n          9. Incidence of gastrointestinal disease that may significantly alter the absorption of\n             Pomalidomide.\n\n         10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment\n\n         11. Any serious medical condition, laboratory abnormality, or psychiatric illness that\n             would prevent the subject from signing the ICD\n\n         12. Pregnant or breastfeeding females\n\n         13. Known human immunodeficiency virus (HIV) positivity; active infectious hepatitis A, B,\n             or C; or chronic hepatitis B or C\n\n         14. For subjects enrolling in Cohort B - Subject has known allergies, hypersensitivity to\n             mannitol, corticosteroids, monoclonal antibodies or human proteins, or their\n             excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived\n             products.
Treatment with weekly single-agent paclitaxel is appropriate in the opinion of the treating physician
Have a clinical indication for treatment as determined by the investigator
No prior treatment except patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids, cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture
No prior treatment with cetuximab
Patients must not have used cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 8 weeks of randomization
Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
Patient is currently deriving clinical benefit from the study treatment, as determined by the investigator.
Patients who do not meet parent protocol criteria to continue study treatment.
No prior systemic treatment for ES-SCLC
Relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
Prior treatment with sorafenib or tivozanib.
Subject must be deriving benefit from continued treatment without any persistent intolerable toxicity from continued treatment of ASP2215.
Subject agrees not to participate in another interventional study while on treatment.
Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment
More than one chemotherapeutic regimen given for R/M disease. Prior treatment with immunotherapy is allowed.
Prior use of cetuximab in the R/M disease treatment setting (except cetuximab during curative radiotherapy)
Prior treatment with either BBI608 or BBI503
Patients who have had previous treatment with:
Previous cancer treatment contraindicates this protocol therapy.
Prior treatment with fulvestrant
Prior treatment with radiotherapy is allowed.
Patients may begin BBI608 on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days since last receiving anti-cancer treatment which did not include BBI608, provided that all treatment-related adverse events have resolved or have been deemed irreversible (except for alopecia).
Prior irinotecan treatment
Previous treatment with Samarium-153 or Strontium-89.
Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 6 weeks prior to first administration of study treatment
The subject with a previous history of a non-invasive carcinoma is eligible if he/she has had successful curative treatment any time prior to Screening.
Inclusion Criteria:\n\n        All Participants:\n\n          -  Confirmed diagnosis of multiple myeloma (MM)\n\n          -  Measurable disease\n\n          -  Archival or newly obtained bone marrow material available. In addition, for\n             participants in the United States (US) and Canada, able to provide newly obtained bone\n             marrow aspirate for biomarker analysis.\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n\n          -  Adequate organ function\n\n          -  Female participants of childbearing potential must be willing to use 2 methods of\n             birth control or be surgically sterile, or abstain from heterosexual activity for the\n             course of the study through 120 days after the last dose of study treatment\n\n          -  Male participants must agree to use a latex condom during sexual contact with females\n             of childbearing potential even if they have had a successful vasectomy starting with\n             the first dose of study treatment through 120 days after the last dose of study\n             treatment\n\n          -  Able to swallow capsules and able to take or tolerate oral medications on a continuous\n             basis\n\n        Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:\n\n          -  Failed at least 2 lines of prior therapy (e.g. bortezomib or carfilzomib and either\n             thalidomide, pomalidomide, or lenalidomide)\n\n          -  Prior anti-MM treatments must have included an immunomodulatory (IMiD) treatment\n             (lenalidomide, pomalidomide or thalidomide) AND proteasome inhibitor (bortezomib or\n             carfilzomib) alone or in combination and participant must have failed therapy with an\n             IMiD OR proteasome inhibitor\n\n          -  Must agree to follow the regional requirements for lenalidomide counseling, pregnancy\n             testing, and birth control; willing and able to comply with the regional requirements\n             (for example, periodic pregnancy tests and safety labs)\n\n        Cohort 2 Participants:\n\n          -  MM with relapsing or refractory disease at study entry\n\n          -  Received prior treatment with 1 to 3 lines for MM\n\n          -  Achieved a partial response to at least one prior regimen (defined as ?50% decrease in\n             tumor burden)\n\n          -  Left ventricular ejection fraction of at least 40%\n\n        Exclusion Criteria:\n\n        All Participants:\n\n          -  Currently participating in and receiving study therapy or has participated in a study\n             of an investigational agent or using an investigational device within 4 weeks of the\n             first dose of study treatment\n\n          -  History of repeated infections; primary amyloidosis; hyperviscosity; plasma cell\n             leukemia; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and\n             skin changes (POEMS) syndrome or Waldenström's macroglobulinemia\n\n          -  Diagnosis of immunosuppressive disorder or on any other immunosuppressive therapy\n             within 7 days prior to the first dose of study treatment\n\n          -  Received a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who\n             has not recovered (i.e. ? Grade 1 or at baseline) from a baseline AE or a Grade 1 AE\n             associated with agents administered more than 4 weeks earlier\n\n          -  Prior anti-MM therapy (including dexamethasone), targeted small molecule therapy, or\n             radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to\n             a previously administered agent\n\n          -  An additional malignancy that is progressing or requires active treatment within the\n             last 5 years\n\n          -  Clinically active central nervous system (CNS) involvement\n\n          -  Active autoimmune disease or a documented history of autoimmune disease, or a syndrome\n             that requires systemic steroids or immunosuppressive agents\n\n          -  Has a history of (non-infectious) pneumonitis that required steroids or current\n             pneumonitis\n\n          -  Active infection requiring intravenous systemic therapy\n\n          -  Known psychiatric or substance abuse disorders that would interfere with cooperation\n             with the requirements of the study\n\n          -  Pregnant or breastfeeding, or expecting to conceive or father children within the\n             projected duration of the study, starting with the pre-screening or screening visit\n             through 120 days after the last dose of study treatment\n\n          -  Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1\n             (anti-PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-Cytotoxic\n             T-lymphocyte-associated antigen-4 (CTLA-4) agent\n\n          -  Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C\n             Virus (HCV) infection\n\n          -  Clinically significant coagulopathy\n\n          -  Known symptomatic congestive heart failure, unstable angina pectoris, or cardiac\n             arrhythmia\n\n          -  Has had or is planning for allogeneic stem cell transplant\n\n          -  Autologous stem cell transplant within 12 weeks before the first infusion\n\n          -  History of Grade 4 rash associated with thalidomide treatment\n\n          -  Known hypersensitivity to thalidomide, lenalidomide or pomalidomide\n\n          -  Received a live vaccine within 30 days of planned start of study treatment\n\n        Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:\n\n          -  Known gastrointestinal disease that may significantly alter the absorption of\n             lenalidomide\n\n          -  Unable or unwilling to undergo antithrombotic prophylactic treatment\n\n        Cohort 2 Participants:\n\n          -  Smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma\n             cell leukemia or Waldenström's macroglobulinemia\n\n          -  Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to the\n             first dose of study treatment\n\n          -  Myocardial infarction within 4 months prior to randomization, New York Heart\n             Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of\n             severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick\n             sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3\n             conduction system abnormalities unless participant has a pacemaker.\n\n          -  Known history of allergy to CAPTISOL® (a cyclodextrin derivative used to solubilize\n             carfilzomib)\n\n          -  Hypersensitivity to carfilzomib, bortezomib, boron, or mannitol\n\n          -  Contraindication to any of the required concomitant drugs or supportive treatments,\n             including hypersensitivity to all anticoagulation and antiplatelet options, antiviral\n             drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment\n\n          -  Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first\n             dose of study treatment\n\n          -  Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14\n             days prior to the first dose of study treatment
Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Subjects must have discontinued use of such agents prior to beginning study treatment.
Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-0610. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive or aggressive subtypes of lymphoma following discussion with the medical monitor.
Prior treatment with rigosertib;
EXCLUSION FOR TREATMENT: Prior neurologic toxicity to previous immunotherapy
Current treatment on another therapeutic clinical trial
History of peptic ulcer disease within 3 months of treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
Prior treatment with lenalidomide
Treatment with other locoregional therapies (other than study treatment) has not been planned for the duration of the clinical study period
Prior yttrium-90 microsphere treatment to the liver
Prior treatment with transarterial chemoembolization (TACE) or bland embolization >2 months prior to randomization and must have been applied to a treatment field and/or lobe not targeted for treatment under this protocol
Treatment for the studied cancer within 28 days prior to initiation of study treatment
Prior treatment with plitidepsin.
Symptomatic arrhythmia (excluding grade ? 2 anemia-related sinusal tachycardia) or any arrhythmia requiring ongoing treatment, and/or prolonged grade ? 2 QT-QTc, or presence of unstable atrial fibrillation. Patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion.
Del(5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as either: 1) having received at least 3 months of lenalidomide treatment without RBC transfusion benefit (International Working Group [IWG] 2006); 2) progression or relapse after hematologic improvement with lenalidomide (IWG 2006); 3) discontinuation of lenalidomide due to toxicity; or 4) unable to receive lenalidomide due to a contraindication. Source documentation for lenalidomide treatment failure must be verified by the sponsor
Patients must have progressed on or within 60 days after end of previous therapy before to study entry, i.e., refractory to the last line of treatment.
All patients who disagree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.
Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
Treatment Naive MCL patients requiring treatment with no exposure to prior therapies. Relapsed/Refractory patients defined as disease relapsed or been refractory to ? 1 prior therapies for MCL and requiring further treatment. Patient who discontinued any prior treatment for MCL for tolerability reasons can also be enrolled.
Have been informed of other treatment options
Prior treatment with lenvatinib.
Has received a front line platinum-based regimen (administered via either intravenous or intraperitoneal route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence (note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment)
Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
Requires intermittent or chronic treatment with antiherpetic drugs, except for topical agents
Has progressed on more than 2 prior treatment regimens for acute GVHD.
Subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles (full therapeutic dose) and must have been deemed as relapsed, refractory, or intolerant. Refractory is defined as progressing on-treatment or within 60 days of the last dose.
Previous treatment with decitabine or azacitidine or other hypomethylating agent.
Live vaccines should ideally not be administered to any patients undergoing treatment with chemotherapy or immunotherapy, but if need be, they should be administered >4 months prior to the initiation of treatment or >4 months after the completion of all treatment
Concomitant treatment with:
For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment
For women who are not postmenopausal or surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than [<] 1 percent [%] per year during the treatment period and for at least 18 months after the last dose of study treatment for participants in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 12 months after the last dose of study treatment for participants in the Atezo-R-CHOP treatment group
Previous systemic chemotherapy is permitted if administered as induction treatment (=< 2 cycles) before definitive chemoradiotherapy for early stage disease and there is no evidence of tumor progression during or after treatment completion
Did not receive any anti-cancer treatment since the last dose of MK-3475
Patients must discontinue treatment with H2-blockers (cimetidine, ranitidine, etc.) prior to beginning protocol therapy
Vaccinated with any of the vaccines planned for administration in the trial within 8 weeks of starting treatment on the study
Prior treatment with a therapeutic agent targeting CD19 and/or CD3
A clinical indication for treatment as determined by the investigator
Ongoing infection that requires parenteral treatment with antibiotics
Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
Previous antiangiogenic treatment
History of prior experimental cancer vaccine treatment (e.g., dendritic cell therapy, heat shock vaccine) within the last year
Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy.
Any prior treatment with carfilzomib
Prior treatment with carfilzomib or oprozomib
More than one previous treatment line with erlotinib, gefitinib or afatinib
Previous first line treatment with at least standard dose of radiotherapy (total dose >= 54 gray [Gy]) and temozolomide
Has prior treatment with Gliadel (carmustine) unless it was administered as first line treatment and at least 3 months prior to study treatment
Current treatment for active connective tissue disorders, such as lupus or scleroderma
Uncontrolled infection; to be eligible, patients receiving treatment for an infection (antibiotic, antifungal or antiviral treatment) must be afebrile (< 38.3 degrees Celsius [C]) and without hemodynamic instability or dyspnea from pneumonia for > 48 hours (hrs) prior to the start of induction therapy
Any cytotoxic chemotherapy,or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen within 14 days of the first dose of study treatment
Current treatment with steroids
Prior treatment with temozolomide, dacarbazine or procarbazine
Have chosen a radical prostatectomy for treatment of their disease after the medical team has presented all possible treatment options
Currently requiring any type of full-dose anti-coagulation treatment, systemic administration of antibiotics or chronic administration of anti-viral agents
Is receiving concomitant treatment with drugs that may interact with capecitabine
Prior treatment with bleomycin
Prior treatment with systemic steroids within 4 weeks prior to lymphodepletion (except for physiologic replacement doses for adrenal insufficiency, premedication for contrast allergies for scans, and for drug fever related to targeted therapy)
Previous treatment with SB-485232 or ofatumumab
Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible
Ongoing treatment with chronic immunosuppressants.
Phase1: Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IV melanoma.
Subjects previously treated with anti-program death-1 (PD1) or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibodies must not have discontinued therapy due to any treatment-related adverse events including immune-related adverse events. Prior treatment-related adverse events should also be fully resolved and not requiring treatment for at least 28 days prior to randomization.
Treatment-naïve
Patients must have been previously treated, as defined by treatment with at least one prior cytotoxic regimen or agent
Prior treatment with cabozantinib
The subject has received radiation therapy:\r\n* To the thoracic cavity or gastrointestinal tract within 3 months before the first dose of study treatment\r\n* To brain metastasis within 14 days before the first dose of study treatment\r\n* To any other site(s), with the exception of bone, within 28 days before the first dose of study treatment
The subject has received radionuclide treatment within 6 weeks before the first dose of study treatment
Subject has had previous treatment with ART-123.
Currently tolerating imatinib 400mg QD. Patients with prior imatinib treatment interruption or dose reductions are required to be on treatment with 400 mg imatinib for two weeks immediately prior to randomization to ensure tolerance to imatinib
TREATMENT
TREATMENT
An infection requiring antibiotic treatment within seven days of starting study treatment (day -1)
Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]
Prior treatment with irinotecan, topotecan, or dinutuximab.
Subject must agree to undergo two research-directed biopsies during treatment
Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), are allowed
Be eligible for treatment with physician's choice of comparator treatment (abiraterone acetate, enzalutamide or docetaxel)
Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting.
Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN) per institutional guidelines, or <55%, if threshold for normal not otherwise specified by institutional guidelines, for patients with the following risk factors: Prior treatment with anthracyclines; Prior treatment with trastuzumab; Prior central thoracic RT, including exposure of heart to therapeutic doses of ionizing RT; History of myocardial infarction within 6-12 months prior to start of IPs; Prior history of other significant impaired cardiac function
Prior treatment with other agents targeting the HGF/c-Met pathway
Subject agrees not to participate in another interventional study while on treatment.
Subject has cholesterol panel and triglyceride done before first treatment
Prior treatment with IMGN779
Prior treatment with neratinib
Have a central venous catheter line in place prior to study treatment administration
Prior treatment in clinical trial UTX-TGR-304
Those with BRAF wild type may have had a maximum of two previous systemic regimens for the treatment of melanoma.
Those with a BRAF mutation may have had a maximum of three previous systemic regimens for the treatment of melanoma.
Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.
Prior treatment with imetelstat
Patients may not have been included in any prior IMCgp100 trial, regardless of treatment cohort
Inclusion Criteria:\n\n          -  Age >= 18 years\n\n          -  Indicated and planned to receive primary radiation therapy for prostate cancer\n\n          -  Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following\n             at diagnosis: 1) Gleason score >=8 and >=cT2c, 2) Gleason score >=7, PSA >=20 nanogram\n             per milliliters (ng/mL), and >=cT2c\n\n          -  Charlson index (CCI) <=3\n\n          -  An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1\n\n          -  Adequate organ function: (1) aspartate aminotransferase (AST), alanine\n             aminotransferase (ALT), within normal limits (WNL), (2) serum creatinine less than (<)\n             1.5 milligram/deciliter (mg/dL) (<133 micromoles/Liter [mcmol/L]), (3) platelets\n             greater than or equal to (>=)140,000/microLiter (mcL), independent of transfusion\n             and/or growth factors within 3 months prior to randomization, (4) Hemoglobin >= 12.0\n             gram/deciliter (g/dL) (7.4 millimloes [mmol], independent of transfusion and/or growth\n             factors within 3 months prior to randomization\n\n          -  Participants who are sexually active (even men with vasectomies) and willing to use a\n             condom and agree not to donate sperm during the trial\n\n          -  Signed, written, informed consent\n\n          -  Be able to swallow whole study drug tablets\n\n        Exclusion Criteria: -\n\n          -  Presence of distant metastasis, (clinical stage M1). Isolated pelvic nodal disease\n             below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of\n             distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal\n             disease (clinical N stage; N1 versus N0) will be assessed by central radiological\n             review. Patients are considered eligible only if the central radiological review\n             confirms clinical stage M0.\n\n          -  Prior treatment with gonadotropin releasing hormone (GnRH) analogue or anti-androgen\n             or both for >3 months prior to randomization\n\n          -  Bilateral orchiectomy\n\n          -  History of pelvic radiation\n\n          -  Prior systemic (example [e.g.], chemotherapy) or local (e.g. radical prostatectomy,\n             cryotherapy) treatment for prostate cancer\n\n          -  History of seizure or any condition that may predispose to seizure (including, but not\n             limited to prior stroke, transient ischemic attack or loss of consciousness <= 1 year\n             prior to randomization; brain arteriovenous malformation; or intracranial masses such\n             as schwannomas and meningiomas that are causing edema or mass effect)\n\n          -  Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone,\n             ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational\n             agents (including cyproterone acetate) for prostate cancer\n\n          -  Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy\n             (e.g., sipuleucel-T) for prostate cancer\n\n          -  Prior treatment with systemic glucocorticoids ?4 weeks prior to randomization or is\n             expected to require long-term use of corticosteroids during the study\n\n          -  Use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) <=4 weeks prior\n             to randomization\n\n          -  Use of any investigational agent <=4 weeks prior to randomization\n\n          -  Current chronic use of opioid analgesics for >=3 weeks for oral or >7 days for\n             non-oral formulations\n\n          -  Major surgery <=4 weeks prior to randomization\n\n          -  Current or prior treatment with anti-epileptic medications for the treatment of\n             seizures\n\n          -  Gastrointestinal conditions affecting absorption\n\n          -  Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide\n             or GnRH agonists or any of the components of the formulations\n\n          -  Any condition for which, in the opinion of the investigator, participation would not\n             be in the best interest of the subject
Prior progesterone treatment for either diagnosis is ALLOWED
Concurrent treatment with estrogens or progestins; patients must stop these drugs at least two weeks prior to study entry
?1 prior systemic hematologic therapy for a free light chain (FLC) producing hematologic malignancy underlying the initial diagnosis of AL amyloidosis with at least a partial FLC response (PR, VGPR, CR) to treatment deemed stable and not requiring further treatment
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma creatine kinase (CK) levels should be avoided while on MEK162 treatment
If the patient has been using the Optune™ device, it will be discontinued at least four days prior to commencing treatment with VAL-083, and the patient must have recovered from all treatment-related toxicities to Grade 1 or less.
Prior treatment with letrozole is allowed if the patient meets the washout period of 10 days.
Prior treatment with anti-CTLA-4 therapeutic antibody or pathway-targeting agents
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
Capecitabine and bevacizumab considered appropriate treatment for the patient
Has a known blood clotting disorder requiring treatment
Previous treatment with ibrutinib
Repeat palliative RT will be permitted for the treatment of isolated, non-target lesions
For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
Patients must have disease progressing after treatment with at least one line of therapy including mitotane and/or chemotherapy; Note: Patients who are deemed ineligible to receive first line treatment with mitotane and/or chemotherapy or who decline first line treatment may be eligible for this study after discussion with the principal investigator (PI)
FOCBP and men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment and the designated post-treatment period
Have completed the required components of the previous study and be appropriate for enrollment into this long-term continued treatment and follow-up study, as determined by the Sponsor
Is receiving other concomitant anticancer treatment
Previous treatment with specific chemotherapy (cytarabine, idarubicin, daunorubicin) or hypomethylating drug (decitabine or azacitidine) for a hematological disorder; EXCEPTIONS: prior hydroxyurea allowed; secondary AML is allowed
Treatment with short-acting somatostatin analogs less than 3 days and Sandostatin depot injection less than 5 weeks before scanning and treatment
Inclusion:\n\n          1. Signed and dated written informed consent prior to any mandatory study specific\n             procedures, sampling and analyses.\n\n          2. Signed and dated written informed consent for tumour biopsies. If the tumour is found\n             not to be safely accessible the biopsy will not be taken. Accessible lesions are\n             defined as those which are biopsiable and amenable to repeat biopsy, unless clinically\n             contraindicated. In this case the patient will remain in the study and there will be\n             no penalty or loss of benefit to the patient and they will not be excluded from other\n             aspects of the study.\n\n          3. Postmenopausal women aged ? 18 years\n\n          4. Negative pregnancy test prior to dosing and willing to use a highly effective method\n             of contraception for the duration of the study and for 90 days after the last dose of\n             IP if they are under 50 unless they have medically confirmed irreversible premature\n             ovarian failure, bilateral oophorectomy, bilateral salpinectomy, or complete or\n             partial hysterectomy.\n\n             Highly effective methods of contraception are:\n\n             • Use of oral, injected or implanted hormonal methods of contraception which inhibit\n             ovulation, either estrogen and progestogen containing intravaginal, transdermal) or\n             only progesterone containing (oral, injectable, implantable)\n\n             • Placement of an intrauterine device (IUD or intrauterine system (IUS)\n\n             • True abstinence\n\n             • Bilateral tubal ligation\n\n             • Vasectomised partner\n\n          5. World Health Organisation/Eastern Cooperative Oncology Group (ECOG) performance status\n             of patient is 0-1 with no deterioration over the previous 2 weeks and minimum life\n             expectancy of 12 weeks.\n\n          6. Histologically or cytologically proven diagnosis of breast cancer with evidence of\n             locally advanced or metastatic disease, not amenable to resection or radiation therapy\n             with curative intent.\n\n          7. Documentation of estrogen receptor positive (ER+) breast cancer based on most recent\n             tumour biopsy (unless bone-only disease).\n\n          8. Documented human epidermal growth factor receptor 2 negative (HER2-) tumor on most\n             recent tumor biopsy.\n\n          9. Where regionally permitted, all patients must agree to provide if available a\n             formalin-fixed paraffin embedded (FFPE) tissue biopsy sample taken at the time of\n             presentation with recurrent or metastatic disease.\n\n         10. At least one lesion (measurable and/or non measurable) that can be accurately assessed\n             at baseline with computerised tomography (CT) or magnetic resonance imaging (MRI)\n             which is suitable for accurate repeated measurements.\n\n         11. Meet the following study part specific criteria related to previous therapy for breast\n             cancer:\n\n        For Part A: Postmenopausal patient suitable for fulvestrant. Patient is allowed to have a\n        maximum of 3 prior lines of chemotherapy. Previous treatment with CDK4/6 inhibitors is\n        allowed\n\n        For Part B: Postmenopausal patient with locally advanced or metastatic ER+ve breast cancer\n        and refractory to AIs defined as:\n\n          -  Disease recurrence while on, or within 12 months of end of adjuvant treatment with\n             letrozole, anastrozole, or exemestane, or\n\n          -  Disease progression while on, or within one month of end of letrozole, anastrozole or\n             exemestane treatment for locally advanced or metastatic breast cancer\n\n               -  Letrozole or anastrozole do not have to be the last treatment prior to\n                  randomization.\n\n               -  Patients who received one prior chemotherapy line for advanced/metastatic breast\n                  cancer are allowed.\n\n        Previous treatment with fulvestrant (or letrozole) is allowed. Other prior anticancer\n        therapy (e.g. tamoxifen) are also allowed.\n\n        For Part C: Postmenopausal patient with locally advanced or metastatic ER+ve breast cancer\n        and refractory to AIs defined as:\n\n          -  Disease recurrence while on, or within 12 months of end of adjuvant treatment with\n             letrozole, anastrozole, or exemestane, ot\n\n          -  Disease progression while on, or within one month of end of letrozole, anastrozole or\n             exemestane treatment for locally advanced or metastatic breast cancer\n\n               -  Letrozole or anastrozole do not have to be the last treatment prior to\n                  randomization.\n\n               -  Patients who received one prior chemotherapy line for advanced/metastatic breast\n                  cancer are allowed.\n\n        Previous treatment with CDK4/6 inhibitors is allowed. Other prior anticancer therapy (e.g.\n        tamoxifen) are also allowed.\n\n        For inclusion in the optional research component:\n\n          1. Genetic research: Provision of signed and dated written consent for genetic research\n             sampling and analyses. If a patient declines to participate in genetic component of\n             the study, there will be no penalty or loss of benefit to the patient. The patient\n             will not be excluded from other aspects of the study described in this Clinical Study\n             Protocol, so long as they consent to the main study.\n\n        Exclusion:\n\n          1. Prior chemotherapy, biological therapy, radiation therapy, or immunotherapy,\n             androgens, thalidomide, other anticancer agents, investigational drug or\n             corticosteroids within 14 days. Patients who received prior radiotherapy to >= 25% of\n             bone marrow are not eligible independent of when it was received. Patients is not\n             eligible if there are unresolved toxicities from prior therapy > CTCAE grade 1 at the\n             start of study treatment with the exception of alopecia.\n\n          2. Exposure to potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) or BCRP\n             within stated washout periods.\n\n          3. Exposure to sensitive or narrow therapeutic range substrates of drug transporters\n             OATP1B1, OATP1B3, MATE1 and MATE2K within wash-out period (5 x elimination half-life).\n\n        4 Exposure to proton pump inhibitors within wash-out period (5 x elimination half-life).\n\n        5. Previous AZD2014, AZD8055 or other dual mTORC1/2 inhibitor\n\n          -  In Part B only: Prior treatment with CDK4/6, or everolimus or any PI3K-mTOR pathway\n\n          -  In Part C only: Prior treatment with fulvestrant, or with everolimus, or any agent\n             whose mechanism of action is to inhibit the PI3K-mTOR pathway\n\n             6. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis,\n             or leptomeningeal disease. Patients with a history of CNS metastases or cord\n             compression are eligible if definitively treated and clinically stable and off\n             anticonvulsants and steroids for at least 4 weeks. Patients are not eligible if there\n             is spinal cord compression and/or brain metastases, unless asymptomatic or treated and\n             stable and off steroids for at least 4 weeks.\n\n             7. Evidence of severe or uncontrolled systemic diseases such as:\n\n             • Severe hepatic impairment\n\n               -  Interstitial lung disease (bilateral, diffuse, parenchymal lung disease)\n\n               -  Current unstable or uncompensated respiratory or cardiac conditions\n\n               -  Uncontrolled hypertension\n\n               -  Active bleeding diatheses\n\n               -  Any active infection\n\n                  8. Other malignancy within 3 years, except adequately treated basal cell or\n                  squamous cell skin cancer, or carcinoma in situ of the cervix\n\n                  9. Experienced any of the following currently or in the last 12 months:\n\n               -  Coronary/peripheral artery bypass graft\n\n               -  Angioplasty\n\n               -  Vascular stent\n\n               -  Myocardial infarction\n\n               -  Angina pectoris\n\n               -  Congestive heart failure NYHA Grade ? 2\n\n               -  Ventricular arrhythmias requiring continuous therapy\n\n               -  Supraventricular arrhythmias including atrial fibrillation of any grade\n\n               -  Symptomatic pulmonary embolism\n\n               -  Haemorrhagic or thrombotic stroke\n\n                  10. Abnormal ECHO or MUGA at baseline (LVEF <50%).\n\n                  11. Mean resting QTc >470 msec, family or personal history of long or short QT\n                  syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de\n                  Pointes within 12 months.\n\n                  12. Clinically important abnormalities in rhythm, conduction or morphology of\n                  resting ECG.\n\n                  13. Hepatitis B (HBV), Hepatitis C (HCV) or Human Immunodeficiency virus (HIV).\n\n                  14. Concomitant medications known to predispose to Torsade de Pointes, or factors\n                  that increase the risk of QT prolongation or risk of arrhythmic events such as:\n\n               -  Heart failure\n\n               -  Hypokalaemia\n\n               -  Congenital long QT syndrome\n\n               -  Family history of long QT syndrome\n\n               -  Family history of unexplained sudden death under 40 years-of-age\n\n                  15. Inadequate bone marrow reserve or organ function as demonstrated by:\n\n               -  ANC <1.5 x 10^9/L.\n\n               -  In Part A only - Cohorts of patients with specific baseline ANC range to be\n                  enrolled defined as follows: I) Low ANC patients: between 1.5 x 10^9/L and 3.0 x\n                  10^9/L; ii) High ANC patients > 3.0 x 10^9/L.\n\n               -  Platelets <100 x 10^9/L\n\n               -  Haemoglobin <90 g/L\n\n               -  ALT >2.5 x ULN or > 5 x ULN in the presence of liver mets.\n\n               -  AST >2.5 x ULN or > 5 x ULN in the presence of liver mets.\n\n               -  Total bilirubin >1.5 x ULN. Total bilirubin >3 x ULN in patients with documented\n                  Gilbert's Syndrome.\n\n               -  Serum creatinine >1.5 x ULN concurrent with creatinine clearance ?50 mL/min.\n\n                  16. Pre-existing renal disease including glomerulonephritis, nephritic syndrome,\n                  Fanconi Syndrome or Renal tubular acidosis.\n\n                  17. Refractory nausea/vomiting, chronic GI diseases, inability to swallow the\n                  product or previous significant bowel resection.\n\n                  18. Hypersensitivity to excipients of AZD2014, Palbociclib or Fulvestrant or\n                  drugs with a similar structure.\n\n                  19. Diabetes Type I or uncontrolled Type II, as defined in WHO 2006 (fasting\n                  serum glucose of > 7.0 mmol/L [126 mg/dL]).\n\n                  20. Patient with advanced/metastatic, symptomatic, visceral spread, that are at\n                  risk of life-threatening complications in the short term including patients with\n                  massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary\n                  lymphangitis, and over 50% of liver involvement in metastases.\n\n                  21. Prior hematopoietic stem cell or bone marrow transplant.\n\n                  22. Regular coumadin therapy. Low-molecular-weight heparin therapy or oral Factor\n                  Xa antagonists are allowed.\n\n                  23. Known abnormalities in coagulation, e.g. bleeding diathesis.\n\n                  24. Hematopoietic growth factors (such as erythropoietin, granulocyte colony\n                  stimulating factor [G-CSF], granulocyte macrophage colony stimulating factor\n                  [GM-CSF]) within 2 weeks prior. Primary prophylactic use of G-CSF is not\n                  permitted.\n\n                  25. Other severe acute or chronic psychiatric condition that may increase the\n                  risks associated with study participation.
Previous treatment with any other compound that targets CD40
Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial
Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), and imaging trials, are allowed
Prior treatment with fulvestrant
Prior treatment with oxaliplatin
No prior therapy with the exception of prior radiation therapy and/or prednisone alone, at the discretion of the investigator based on current diagnosis and clinical condition; this prednisone treatment will not count toward the 6 cycles of treatment given in the study
No prior treatment with carmustine wafers
Subject agrees not to participate in another interventional study while on treatment.
The subject with a previous history of a noninvasive carcinoma is eligible if in the opinion of the investigator he/she has had successful curative treatment any time prior to Screening and requires no further therapy for the malignancy.
New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment\r\n* Addition of a new systemic immune suppressive treatment simultaneously with ixazomib is also prohibited
Chronic treatment with glucocorticoids within one year
New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment
Prior systemic cytotoxic chemotherapies and/or novel immunotherapy treatments for MCC are allowed. A wash-out period of 2 weeks prior to aNK treatment will be required.
Prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones; the participant has received treatment with olaratumab or has participated in a prior olaratumab trial.
Actively breastfeeding women unless it is interrupted during treatment and at least 6 weeks after treatment discontinuation
biologic therapy (e.g., bevacizumab) as part of their primary treatment regimen or part of their treatment for management of recurrent or persistent disease.
Prior treatment with dasatinib
Prior treatment with PM01183, trabectedin, or with both PLD and topotecan.
Any prior treatment with T-DM1 (trastuzumab emtansine) or any trastuzumab therapy
Prior treatment with either carfilzomib or oprozomib
ELIGIBILITY FOR TREATMENT ON ARM 1: Ninety days must have passed since the last doses of radiation or chemoradiation treatment involving lung tissue or thorax prior to T cell infusion (to avoid confounding pneumonitis)
ELIGIBILITY FOR TREATMENT ON ARM 2: Ninety days must have passed since the last definitive doses of radiation or chemoradiation treatment prior to T cell infusion (to avoid confounding pneumonitis)
Documented infections or known oral temperature > 38.2 degrees Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance; the start of treatment may be delayed
Patients willing to have regular blood draws, one before treatment and four during or after treatment
Progression or recurrence after treatment
Prior enzalutamide, abiraterone acetate, aminoglutethimide, ketoconazole, radium Ra 223 dichloride or other bone-targeting radionuclides, or cytotoxic chemotherapy in the CRPC setting for the treatment of prostate cancer or participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless treatment was placebo);
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Prior treatment with regorafenib
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Prior treatment with ibrutinib
Any number of prior treatment regimens is allowed
Current treatment or known prior treatment with ribavirin
Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce torsades de pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
Prior treatment with cetuximab or panitumumab
Subject must have received no prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Subject may have been treated for prior Myelodysplastic Syndrome.
Patient plans to receive treatment at MD Anderson
Patients who have received prior systemic anti-cancer treatment, such as cyclical chemotherapy or biological therapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment
Patients receiving anti-herpes medication within 1 week prior to initiating HF10 treatment.
Prior radiotherapy to the region of the body that would result in overlap of RT fields with the current protocol treatment
Patients who have had previous treatment with selinexor
Prior systemic treatment with an azole drug within four weeks of screening visit
Inclusion Criteria: Provision of signed and dated, written informed consent prior to any\n        mandatory study specific procedures, sampling and analyses. Aged at least 18 years. Any\n        menopausal status. Pre- or peri-menopausal women must have commenced treatment with an LHRH\n        agonist at least 4 weeks prior to starting study treatment and must be willing to continue\n        to receive LHRH agonist therapy for the duration of the trial. Histological or cytological\n        confirmation of adenocarcinoma of the breast. ER-positive according to local laboratory;\n        HER-2 negative. Metastatic disease or locoregionally recurrent disease which is not\n        amenable to treatment with curative intent. Disease progression after at least 6 months of\n        endocrine therapy for ER+ breast cancer. Radiological or objective evidence of progression\n        on or after the last systemic therapy prior to starting study treatment. Receipt of ?2\n        lines of prior chemotherapy for advanced disease. Females of child-bearing potential must\n        agree to use adequate contraceptive measures, must not be breast feeding and must have a\n        negative pregnancy test prior to start of dosing. Eastern Cooperative Oncology Group (ECOG)\n        performance status 0-1 with no deterioration over the previous 2 weeks and minimum life\n        expectancy of 12 weeks.\n\n        Exclusion Criteria: Any cytotoxic chemotherapy, investigational agents or other anti-cancer\n        drugs for the treatment of advanced breast cancer from a previous treatment regimen or\n        clinical study within 14 days of the first dose of study treatment. Any unresolved\n        toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events\n        (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia.\n        Presence of life-threatening metastatic visceral disease, uncontrolled central nervous\n        system metastatic disease or symptomatic pulmonary lymphangitic spread. Any evidence of\n        severe or uncontrolled systemic diseases, including uncontrolled hypertension, active\n        bleeding diatheses, or active infection. Unexplained symptomatic endometrial disorders.\n        Uncontrolled symptomatic thyroid dysfunction. Inadequate bone marrow reserve or organ\n        function
Concurrent radiotherapy is not permitted for disease progression on treatment on protocol; however, symptomatic treatment for pre-existing non-target lesions would be allowed with approval from the principal investigator
Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, Sunitinib, Pazopanib, Axitinib, Tivozanib, and Bevacizumab)
Prior treatment with bosutinib.
Prior treatment with ponatinib.
In the opinion of the invesgator likely to complete ? 8 weeks of treatment.
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Prior treatment with pertuzumab, Lapatinib, and/or Trastuzumab emtansine is allowed; however, the last treatment for MBC must not include Trastuzumab in combination with pertuzumab.
No limit on number or type of prior therapies\r\n* Prior treatment with docetaxel is permitted but not required\r\n* Prior treatment with ketoconazole, estrogens, abiraterone or novel antiandrogens allowed, including past enzalutamide\r\n* Require at least a 6 week withdrawal period from the last dose of bicalutamide, or nilutamide or 4 weeks from last flutamide or enzalutamide dose\r\n** Must have a documented PSA rise after stopping the antiandrogen\r\n* Will require a 2 week washout period from last dose of ketoconazole, chemotherapy, radiation (including radium-223), or prior investigational systemic agents
Prior treatment with enzalutamide
Prior cytotoxic chemotherapy with the exception of docetaxel or cabazitaxel; treatment with docetaxel or cabazitaxel must be discontinued >= 4 weeks from the time of enrollment, and recovery of adverse events (AEs) to grade 1 or baseline (however, ongoing neuropathy is permitted)
For inclusion in the study patient should fulfil the following criteria:\n\n          1. Male or female, aged at least 18 years.\n\n          2. Histological or cytological confirmation diagnosis of NSCLC.\n\n          3. Radiological documentation of disease progression while on a previous continuous\n             treatment with an EGFR TKI, eg gefitinib, afatinib or erlotinib. In addition, other\n             lines of therapy may have been given. All patients must have documented radiological\n             progression on the last treatment administered prior to enrolling in the study.\n\n          4. Confirmation that the tumour harbours an EGFR mutation known to be associated with\n             EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration\n             over the previous 2 weeks (Appendix G).\n\n          6. Patients must have a life expectancy of ?12 weeks as estimated at the time of\n             screening.\n\n          7. Females should be using adequate contraceptive measures and must have a negative\n             pregnancy test prior to start of dosing if of child-bearing potential, or must have\n             evidence of non-child-bearing potential by fulfilling one of the following criteria at\n             screening: Post-menopausal defined as aged more than 50 years and amenorrhoeic for at\n             least 12 months following cessation of all exogenous hormonal treatments; women under\n             50 years old would be considered post-menopausal if they have been amenorrhoeic for 12\n             months or more following cessation of exogenous hormonal treatments and with LH and\n             FSH levels in the post-menopausal range for the institution; documentation of\n             irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or\n             bilateral salpingectomy, but not tubal ligation.\n\n          8. Male patients should be willing to use barrier contraception, ie, condoms, until 6\n             months after last study drug is taken.\n\n        Exclusion criteria:\n\n          1. Participation in another study with an IP during the last 14 days (or a longer period\n             depending on the defined characteristics of the agents used).\n\n          2. Treatment with any of the following: Treatment with an EGFR TKI (eg, erlotinib or\n             gefitinib) within 8 days or approx. 5 x half-life, whichever is the longer, of the\n             first dose of study treatment; any cytotoxic chemotherapy, investigational agents or\n             other anticancer drugs from a previous treatment regimen or clinical study within 14\n             days of the first dose; major surgery (excluding placement of vascular access) within\n             4 weeks of the first dose of study treatment; radiotherapy with a limited field of\n             radiation for palliation within 1 week of the first dose of study treatment, with the\n             exception of patients receiving radiation to more than 30% of the bone marrow or with\n             a wide field of radiation which must be completed within 4 weeks of the first dose;\n             patients currently receiving (or unable to stop use prior to receiving the first dose\n             of study treatment) medications or herbal supplements known to be potent inhibitors of\n             CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior).\n             All patients must avoid concomitant use of any medications, herbal supplements and/or\n             ingestion of foods with known inducer/inhibitory effects on CYP3A4.\n\n          3. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of\n             starting study treatment with the exception of alopecia and Grade 2, prior\n             platinum-therapy related neuropathy.\n\n          4. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,\n             or other products containing grapefruit or Seville oranges within 7 days of the first\n             administration of the IP until the final PK sample collection on Day 32 of Part A.\n\n          5. Spinal cord compression or brain metastases unless asymptomatic, stable and not\n             requiring steroids for at least 4 weeks prior to start of study treatment.\n\n          6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled\n             hypertension and active bleeding diatheses, which in the PI's opinion makes it\n             undesirable for the patient to participate in the study or which would jeopardise\n             compliance with the protocol, or active infection including hepatitis B, hepatitis C,\n             and HIV. Screening for chronic conditions not required.\n\n          7. Inadequate bone marrow reserve or organ function as demonstrated by any of the\n             following laboratory values: ANC <1.5 x 10^9/L; platelet count <100 x 10^9/L;\n             haemoglobin <90 g/L; ALT >2.5 times ULN if no demonstrable liver metastases or >5\n             times ULN in the presence of liver metastases; Aspartate aminotransferase (AST) >2.5\n             times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver\n             metastases; total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in\n             the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or\n             liver metastases; creatinine >1.5 times ULN concurrent with creatinine clearance <50\n             ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of\n             creatinine clearance is only required when creatinine is >1.5 times ULN.\n\n          8. Any of the following cardiac criteria: mean resting corrected QT interval corrected\n             for heart rate using Fridericia's correction factor (QTcF) >470 msec obtained from 3\n             ECGs; any clinically important abnormalities in rhythm, conduction or morphology of\n             resting ECG eg, complete left bundle branch block, third degree heart block, second\n             degree heart block, PR interval >250 msec; any factors that increase the risk of QTc\n             prolongation or risk of arrhythmic events such as heart failure, hypokalaemia,\n             congenital long QT syndrome, family history of long QT syndrome or unexplained sudden\n             death under age of 40 or any concomitant medication known to prolong the QT interval.\n\n          9. Patients unable to swallow oral medication or patients with GI disorders or\n             significant GI resection likely to interfere with the absorption of AZD9291.\n\n         10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required\n             steroid treatment, or any evidence of clinically active ILD.\n\n         11. Women who are breastfeeding.\n\n         12. Patients with a known hypersensitivity to AZD9291, simvastatin, or any of the\n             excipients of the products.\n\n         13. Concomitant medication contraindicated for use with simvastatin due to drug\n             interaction associated with increased risk of rhabdomyolysis (including, but not\n             limited to): itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin,\n             telithromycin, HIV protease inhibitors (eg, nelfinavir), nefazodone, cyclosporine,\n             danazol, gemfibrozil, amiodarone, amlodipine.\n\n         14. 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors, such as\n             lovastatin and simvastatin.\n\n         15. For optional genetic research: Previous allogenic bone marrow transplant or\n             non-leukocyte depleted whole blood transfusion within 120 days of the date of the\n             genetic sample collection.
Current treatment with sirolimus AND either cyclosporine or tacrolimus.
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
A confirmed diagnosis of WM, which requires treatment.
Previous treatment with pomalidomide
Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor Eligibility Criteria for Open-label Substudy Treatment Arm C The Inclusion/Exclusion criteria for the substudy (Arm C) are identical to those described above for the randomized study but, to be eligible, subjects need to be considered refractory to the last prior rituximab-containing therapy defined as either
Subjects should be willing to undergo a research related biopsy prior to treatment and at the time of progression
Unable to receive prophylactic treatment for pneumocystis
Treatment with more than one prior line of treatment for advanced NSCLC
Systemic therapeutic radionuclide delivery within 30 days prior to treatment
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment; patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment, should also be excluded; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment
Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment; NOTE: muscular activities, such as strenuous exercise, that can result in significant increases in plasma creatine kinase (CK) levels should be avoided whilst on LDE225 treatment
Treatment naïve or have failed on previous treatment for PRCC. Previous treatments may include: targeted therapy (i.e. sunitinib, sorafenib, bevacizumab, pazopanib, temsirolimus, and everolimus), traditional immunotherapy (i.e. interferon-a, Interleukin-2), chemotherapy or a combination of chemoimmunotherapy.
Prior treatment with a cancer vaccine for this indication
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Dose-escalation: prior treatment with abiraterone acetate; at least 4 weeks must have elapsed from the last dose of abiraterone acetate
Previous treatment with 2 or more courses of decitabine (all stages) or azacitidine (Dose Confirmation stage only)
Prior treatment with nab-paclitaxel.
Requirement for RBC transfusion while on ruxolitinib treatment, OR
Dose adjustment of ruxolitinib to < 20 mg twice daily at start of or during ruxolitinib treatment AND at least one of the following while on ruxolitinib treatment:
Prior treatment with MMB
Radiotherapy to >= 3 sites at the same time within 1 week prior to the first day of treatment
Acute active infection requiring treatment (IV antibiotics, antivirals, or antifungals) within 14 days prior to the first day of treatment
Patients with prior or current treatment of sorafenib are excluded
Current treatment on another therapeutic clinical trial
Prior treatment with bortezomib
Patients who have not recovered from toxicities of prior therapy to the point that they would be appropriate for re-dosing will be ineligible for study treatment; all patients must have a two week washout period from prior chemotherapy
Male and female, ages 18 and above, with relapsed or refractory FL lymphoma after > or =2 prior treatment lines; each of the 2 prior treatment lines must include at least CD20 antibody and/or an alkylating agent
Inclusion Criteria\n\n        Each participant must meet all the following inclusion criteria to be enrolled in the\n        study:\n\n          1. Male or female participants ? 18 years old.\n\n          2. Have a pathologically (histology or cytology) confirmed diagnosis of SCLC.\n\n          3. Have received and progressed after a platinum-based standard chemotherapy regimen for\n             first line treatment of SCLC, either limited stage (LS) or extensive stage (ES).\n\n          4. Have measurable disease within ? 2 weeks before randomization. Clear radiographic\n             evidence of disease progression after initial therapy should have been documented.\n\n          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0-1).\n\n          6. Participants with treated brain metastases (surgery, whole or stereotactic brain\n             radiation) are allowed provided the lesions have been stable for at least 2 weeks and\n             the participant is off steroids or is on a stable dose of steroids. Participants\n             should be without neurologic dysfunction that would confound the evaluation of\n             neurological and/or other AEs.\n\n        Exclusion Criteria\n\n        Participants meeting any of the following exclusion criteria are not to be randomized to\n        treatment:\n\n          1. Any prior therapy for second-line treatment of SCLC.\n\n          2. Participants who relapsed ? 180 days after their response to first-line treatment.\n\n          3. Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent,\n             including alisertib, or any other investigational agent.\n\n          4. Prior treatment with paclitaxel or any other taxane agent.\n\n          5. Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.\n\n          6. Any comorbid condition or unresolved toxicity that would preclude administration of\n             alisertib or weekly paclitaxel.\n\n          7. Prior history of ? Grade 2 neurotoxicity that is not resolved to ? Grade 1.\n\n          8. Participants with symptomatic and/or progressive brain metastases or with\n             carcinomatous meningitis.\n\n          9. Treatment with clinically significant enzyme inducers within 14 days prior to the\n             first dose of alisertib and during study conduct. Major prohibited enzyme inducers\n             include: phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine,\n             and St. John's wort.\n\n         10. Inability to swallow alisertib or other orally administered medications.\n\n         11. Requirement for administration of proton pump inhibitor (PPI), H2 antagonist, or\n             pancreatic enzymes.\n\n         12. Diagnosed with or treated for another malignancy within 2 years before the first dose\n             of study drug, or previously diagnosed with another malignancy and have any evidence\n             of residual disease.\n\n         13. Other severe acute or chronic medical or psychiatric condition(s) per protocol.\n\n         14. History of myocardial infarction, unstable symptomatic ischemic heart disease,\n             uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac\n             arrhythmias of Grade > 2, thromboembolic events (eg, deep vein thrombosis, pulmonary\n             embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg,\n             pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving\n             the first dose of study drug.\n\n         15. Known history of human immunodeficiency virus (HIV) infection, hepatitis B or\n             hepatitis C.\n\n         16. Surgery within 3 weeks (or 2 weeks for a minor surgery) before study enrollment and\n             not fully recovered to baseline or to a stable clinical status.\n\n         17. Participants who are pregnant, lactating, or do not agree to use effective methods of\n             contraception during the study treatment period through 6 months after the last dose\n             of study drug per protocol.
Inclusion Criteria\n\n        Patients must meet the following criteria to be eligible for the study:\n\n          1. Metastatic breast cancer, documented as HER2+ by fluorescence in situ hybridization\n             (FISH) and/or 3+ staining by immunohistochemistry (IHC).\n\n          2. Progressive disease, with a history of prior treatment with both trastuzumab and T-DM1\n             (unless deemed intolerant to or ineligible for T-DM1 by the investigator) for\n             metastatic disease.\n\n          3. ? 18 years at time of consent.\n\n          4. If female and of child-bearing potential, has negative pregnancy test within 14 days\n             prior to treatment.\n\n          5. If a sexually active male or a sexually active female of child-bearing potential,\n             agrees to use dual (two concurrent) forms of medically accepted contraception from the\n             time of consent until 6 months after the last dose of ONT-380, capecitabine, or\n             trastuzumab, whichever is longest.\n\n          6. Signed an informed consent document that has been approved by an institutional review\n             board or independent ethics committee (IRB/IEC).\n\n          7. Must have target or non-target lesions as per Response Evaluation Criteria In Solid\n             Tumors (RECIST) 1.1.\n\n          8. All toxicity related to prior cancer therapies must have resolved to ? Grade 1, with\n             the following exceptions: alopecia; neuropathy, which must have resolved to ? Grade 2;\n             and congestive heart failure (CHF), which must have been ? Grade 1 in severity at the\n             time of occurrence and must have resolved completely.\n\n          9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.\n\n         10. In the opinion of the Investigator, life expectancy > 6 months.\n\n         11. Adequate hematologic function as defined by:\n\n               1. Hemoglobin ? 9 g/dL\n\n               2. Absolute neutrophil count (ANC) ? 1000 cells/?L\n\n               3. Platelets ? 100,000/?L\n\n         12. Adequate hepatic function as defined by the following:\n\n               1. Total bilirubin ? 1.5 X upper limit of normal (ULN), unless a known history of\n                  Gilbert's disease\n\n               2. Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase\n                  [AST/SGOT] and alanine aminotransferase/serum glutamic pyruvic transaminase\n                  [ALT/SGPT]) ? 2.5 X ULN (< 5 X ULN if liver metastases are present)\n\n         13. International normalized ratio (INR) and activated partial thromboplastin time (aPTT)\n             ? 1.5 X ULN unless on medication known to alter INR and aPTT.\n\n         14. Creatinine clearance ? 50 mL/min.\n\n         15. Left ventricular ejection fraction (LVEF) must be within institutional limits of\n             normal as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)\n             documented within 4 weeks prior to first dose of study drug.\n\n        Exclusion Criteria\n\n        Patients will be excluded from the study for any of the following reasons:\n\n          1. Medical, social, or psychosocial factors that, in the opinion of the Investigator,\n             could impact safety or compliance with study procedures.\n\n          2. Patient is breastfeeding.\n\n          3. Previous treatment with any experimental agent within 14 days or five half-lives of\n             study treatment, whichever is greater.\n\n          4. Previous treatment with trastuzumab or other antibody-based therapy within three weeks\n             of starting study treatment or with chemotherapy or hormonal cancer therapy within two\n             weeks of starting study treatment.\n\n          5. Previous treatment with cumulative dose of doxorubicin > 360 mg/m2 or previous\n             treatment with another anthracycline with cumulative dose equivalent to > 360 mg/m2\n             doxorubicin.\n\n          6. Previous treatment with:\n\n               1. Capecitabine for metastatic disease at any time, for patients assigned to cohorts\n                  using capecitabine plus ONT-380 (Combination 1) or capecitabine plus trastuzumab\n                  plus ONT-380 (Combination 3). However, patients who have previous treatment with\n                  capecitabine for metastatic disease are eligible for enrollment into cohorts\n                  using trastuzumab plus ONT-380 (Combination 2). Patients who have received\n                  capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to\n                  starting study treatment are eligible to enroll into all cohorts (Combination 1,\n                  2, or 3).\n\n               2. Any small molecule HER2 inhibitors including (but not limited to) lapatinib,\n                  neratinib, or afatinib within the last 4 weeks prior to initiation of study\n                  therapy.\n\n          7. CNS disease:\n\n               1. Patients with leptomeningeal disease are excluded.\n\n               2. Dose escalation and expansion cohorts: Patients with symptomatic CNS metastases\n                  are excluded. Patients with treated CNS metastases or untreated asymptomatic CNS\n                  metastases not requiring immediate local therapy may be eligible. Enrollment of\n                  patients with metastases must be approved by the study medical monitor.\n\n               3. Optional CNS disease expansion cohorts: Patients with untreated asymptomatic CNS\n                  metastases not requiring immediate local therapy or patients with progressive CNS\n                  disease following local therapy may be eligible with medical monitor approval.\n\n          8. History of allergic reactions to compounds of similar chemical or biological\n             composition to capecitabine (for patients assigned to Combination 1 or 3 only),\n             trastuzumab (for patients assigned to Combination 2 or 3 only), or ONT-380, except for\n             a history of Grade 1 or Grade 2 Infusion Related Reaction to trastuzumab, which has\n             been successfully managed.\n\n          9. Patients with uncorrectable electrolyte abnormalities.\n\n         10. Known to be HIV positive. HIV testing is not required for those patients who are not\n             known to be positive.\n\n         11. Known carrier of Hepatitis B and / or Hepatitis C (whether active disease or not).\n\n         12. Known liver disease, autoimmune hepatitis, or sclerosing cholangitis.\n\n         13. Inability to swallow pills or any significant gastrointestinal diseases, which would\n             preclude adequate absorption of oral medications.\n\n         14. Use of a strong CYP3A4 inhibitor or inducer within three elimination half-lives of the\n             inhibitor or inducer prior to the start of study treatment.\n\n         15. Use of a strong CYP2C8 inducer or inhibitor within three elimination half-lives of the\n             inducer or inhibitor prior to the start of study treatment. (See Appendix F).\n\n         16. Radiotherapy within 14 days of first dose of ONT-380; patient must have recovered from\n             acute effects of radiotherapy to baseline.\n\n         17. Known impaired cardiac function or clinically significant cardiac disease such as\n             ventricular arrhythmia requiring therapy, congestive heart failure, and uncontrolled\n             hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood\n             pressure > 100 mmHg on antihypertensive medications).\n\n         18. Myocardial infarction or unstable angina within 6 months prior to the first dose of\n             study drug.\n\n         19. Patient with known dihydropyrimidine dehydrogenase deficiency (for patients assigned\n             to Combination 1 or 3 only).\n\n         20. Patient requiring warfarin therapy with known history of difficulty in management of\n             maintaining INR within therapeutic range. Patients on warfarin may be included if on a\n             stable dose with a therapeutic INR.
Advanced unresectable, metastatic or recurrent colorectal carcinoma (CRC) for which treatment with FOLFOX6 with or without bevacizumab, FOLFIRI with or without bevacizumab, CAPOX, or regorafenib would be acceptable as determined by the Investigator. FOLFIRI-refractory patients with CRC enrolling on the FOLFIRI study arm must have failed treatment with one FOLFIRI with or without bevacizumab regimen for unresectable or metastatic disease. Treatment failure is defined as progression of disease (clinical or radiologic) during treatment with FOLFIRI with or without bevacizumab or < 3 months after the last dose of treatment with FOLFIRI with or without bevacizumab. Patients with CRC enrolling on the regorafenib arm of this study will have previously received at least two previous lines of therapy for advanced colorectal cancer, and will have previously received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Patients with K-ras wild type tumors enrolling on the regorafenib arm will also have previously received either cetuximab or panitumumab.
Prior treatment with BBI608.
Prior treatment with radium-223 dichloride
Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
Prior bevacizumab or other Vascular Endothelial Growth Factor (VEGF) or anti-angiogenic treatment (Cohort 2 only)
Prior hypomethylating agent treatment for MDS
Prior treatment with a cancer vaccine for this indication
History of prior venetoclax treatment
Prior treatment with eribulin, fulvestrant or anastrozole, paclitaxel, abraxane, docetaxel, vinorelbine, or capecitabine
Prior treatment of any duration with pomalidomide
Inclusion Criteria:\n\n        All Participants:\n\n          -  At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5\n             centimeters (cm) in its longest dimension\n\n          -  Life expectancy of at least 24 weeks\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2\n\n          -  Adequate hematologic function (unless inadequate function is due to underlying\n             disease, as established by extensive bone marrow involvement or is due to\n             hypersplenism secondary to the involvement of the spleen by lymphoma per the\n             investigator)\n\n          -  Agreement to use highly effective contraception measures. Women of childbearing\n             potential must agree to remain abstinent or use contraceptive measures that result in\n             a failure rate of <1 percent (%) per year during the treatment period and for at least\n             12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of\n             study drug. Men must agree to remain abstinent or to use a condom plus an additional\n             contraceptive method that together result in a failure rate of <1% per year during the\n             treatment period and for at least 5 months after the last dose of study drug\n\n        Dose-Escalation Portion of the Study:\n\n          -  Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or\n             relapsed/refractory B-cell NHL are eligible\n\n          -  No more than one prior systemic treatment regimen for B-cell NHL (single agent\n             anti-cluster of differentiation [CD] 20 monoclonal antibody therapy will not be\n             counted as a prior treatment regimen)\n\n          -  No prior treatment with anthracyclines\n\n        Expansion Portion of the Study:\n\n          -  Previously untreated participants with diffuse large B-cell lymphoma (DLBCL)\n\n          -  International Prognostic Index score of 2-5\n\n        Exclusion Criteria:\n\n        Dose-Escalation Portion of the Study:\n\n          -  Diagnosis of primary mediastinal DLBCL\n\n        Expansion Portion of the Study:\n\n          -  Participants with transformed lymphoma\n\n          -  Prior therapy for NHL\n\n        All Participants:\n\n          -  Prior stem cell transplant\n\n          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal\n             antibodies or known sensitivity or allergy to murine products\n\n          -  Contraindication to receive any of the individual components of R-CHP or G-CHP\n\n          -  Current Grade greater than (>) 1 peripheral neuropathy\n\n          -  Ongoing corticosteroid use of >30 milligrams per day (mg/day) of\n             prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment\n             with less than or equal to (</=) 30 mg/day of prednisone//prednisolone or equivalent\n             must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1\n             Day 1\n\n          -  Primary central nervous system (CNS) lymphoma\n\n          -  Vaccination with live vaccines within 6 months before Cycle 1 Day 1\n\n          -  History of other malignancy that could affect compliance with the protocol or\n             interpretation of results. Participants with a history of curatively treated basal or\n             squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are\n             eligible. Participants with a malignancy that has been treated with surgery alone with\n             curative intent will also be excluded unless the malignancy has been in documented\n             remission without treatment for greater than or equal to (</=) 5 years before\n             enrollment\n\n          -  Evidence of significant, uncontrolled concomitant diseases, including renal disease\n             that would preclude chemotherapy administration, or pulmonary disease (including\n             obstructive pulmonary disease and history of bronchospasm)\n\n          -  Significant cardiovascular disease (such as New York Heart Association Class III or IV\n             cardiac disease, congestive heart failure, myocardial infarction within the previous 6\n             months, unstable arrhythmias, or unstable angina) or significant pulmonary disease\n\n          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection\n             (excluding fungal infections of nail beds) at study enrollment or any major episode of\n             infection requiring treatment with IV antibiotics or hospitalization (relating to the\n             completion of the course of antibiotics) within 4 weeks before Cycle 1 Day 1\n\n          -  Clinically significant history of liver disease, including viral or other hepatitis,\n             current alcohol abuse, or cirrhosis\n\n          -  Positive for hepatitis B or hepatitis C infection\n\n          -  Prior radiotherapy to the mediastinal/pericardial region\n\n          -  Pregnant or lactating women\n\n          -  Recent major surgery within 6 weeks before the start of Cycle 1 Day 1\n\n          -  Abnormal laboratory values
Previous laser therapy within one year prior to protocol treatment
Previous treatment with T-DM1 at any time; or previous treatment with any small molecule HER2 inhibitors including (but not limited to) lapatinib, neratinib, or afatinib within the last 4 weeks prior to initiation of study therapy.
Alemtuzumab treatment within 8 weeks of HSCT admission
Subject agrees not to participate in another interventional study while on treatment.
Have been informed of other treatment options.
Prior neck and/or upper thoracic radiotherapy that would cause an overlap of treatment fields
At least 1 prior treatment with a CD20 antibody combination chemo-immunotherapy regimen
Prior treatment according to protocol-defined criteria
Previous treatment in the present study.
Last radiotherapy treatment >= 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation
Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of cycle 1, day 1
Prior flutamide (Eulexin) treatment within 4 weeks of cycle 1, day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to cycle 1, day 1)
Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
Subject agrees not to participate in another interventional study while on treatment.
Additional experimental anti-cancer treatment and/or standard chemo-, immunotherapy, hormone treatment (with the exception of megestrol acetate), or concurrent radiotherapy is not allowed concomitantly with the administration of study treatment; 89Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted
Concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. Bisphosphonates are permitted without restriction even during protocol treatment.
Anticancer treatment (e.g., radiation therapy, chemotherapy) within 21 days of first dose\r\n* An exception is cetuximab treatment, which can be received within 21 days of the first treatment on study.
Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances.
Willingness to undergo pre- and on-treatment biopsies unless not clinically feasible while on treatment
Treatment with systemic immunostimulatory agents
Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
For phase II, up to 4 prior chemotherapy-based treatments are allowed; patients must have had prior trastuzumab-based therapy; prior neratinib treatment is not permitted; prior capecitabine is allowed, if not combined with neratinib
Has a previous treatment with irinotecan
Inclusion Criteria: All subjects\n\n          1. Unsuitable for chemoimmunotherapy with FCR in the opinion of the investigator.\n\n          2. Confirmed diagnosis of CD20-positive CLL or SLL.\n\n          3. Binet Stage C disease, or Binet Stage B or A disease requiring treatment.\n\n          4. ECOG performance status of 0, 1 or 2.\n\n          5. Life expectancy ? 6 months.\n\n          6. Adequate bone marrow function.\n\n          7. Adequate renal and hepatic function.\n\n          8. Females of childbearing potential and non-sterile males must agree to use highly\n             effective methods of birth control throughout the course of study\n\n          9. Male patients are eligible if vasectomized or if they agree to use of barrier\n             contraception with other methods described above throughout the course of study.\n\n         10. Written informed consent.\n\n        Exclusion Criteria: All subjects\n\n          1. Previous systemic treatment for CLL/SLL.\n\n          2. Known prolymphocytic leukemia or history of or suspected Richter's transformation.\n\n          3. Clinically significant cardiovascular disease.\n\n          4. Prior malignancy within the past 3 years, except for curatively treated basal or\n             squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the\n             cervix of breast.\n\n          5. Major surgery or significant injury ? 4 weeks prior to start of study treatment.\n\n          6. History of severe bleeding disorder.\n\n          7. History of stroke or intracranial hemorrhage within 6 months before the first dose of\n             study drug.\n\n          8. Severe or debilitating pulmonary disease.\n\n          9. Inability to swallow capsules or disease affecting gastrointestinal function.\n\n         10. Known central nervous system involvement by leukemia or lymphoma.\n\n         11. Active infection requiring systemic treatment.\n\n         12. Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C\n             infection.\n\n         13. Vaccination with live vaccine within 35 days prior to the first dose of study drug.\n\n         14. Known hypersensitivity to BGB-3111, bendamustine, or rituximab or any other\n             ingredients of the study drugs.\n\n         15. Requires ongoing treatment with strong CYP3A inhibitor or inducer.\n\n         16. Pregnant or nursing females.\n\n         17. Concurrent participation in another therapeutic clinical trial.
Prior treatment with any gene therapy product
Phase 1b: Participants with AML who are refractory to or have relapsed after initial treatment for their disease, with no more than three prior lines of therapy. Participants who have received prior treatment with cytarabine or decitabine are not excluded.
Palliative radiotherapy must have been discontinued 1 week prior to treatment in this study
Prior treatment with second generation anti-androgens
Prior treatment with enzalutamide
Prior treatment with abiraterone acetate or enzalutamide
Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of cycle 1, day 1
PART A: Able (physically and financially) to travel to University of Colorado for clinical trial treatment
No acute toxicities from previous treatment higher than grade 1 at the start of treatment with CPI-613
Treatment with any anti-cancer therapy within the 2 weeks prior to treatment with CPI-613
Prior treatment with Aurora A-targeted agents, including MLN8237
Prior treatment with irinotecan or aurora A-targeted agents, including MLN8237
Subjects who are refractory to initial induction or re-induction treatment
Prior treatment with four or more cycles of hypomethylator therapy
Concurrent treatment on another clinical trial; supportive care trials or non-treatment (i.e. quality of life) are allowed
Other than ongoing ADT, prior treatment with other hormonal agents such as antiandrogens or ketoconazole must have been stopped at least two weeks prior to enrollment
Prior treatment with enzalutamide, TOK-001, or ARN-509; prior therapy with abiraterone or orteronel is permitted, but must have been stopped a minimum of two weeks prior to study entry; prior and/or concurrent treatment with bone-targeted therapy such as bisphosphonates or denosumab is permitted
The most recent treatment prior to enrollment must be one of the following (duration of treatment >= 2 weeks), and must have been adequately tolerated according to the treating physician's judgment\r\n* Letrozole\r\n* Exemestane\r\n* Exemestane + everolimus (everolimus must be discontinued for >= 3 weeks prior to starting study treatment)\r\n* Letrozole or exemestane in combination with an experimental agent(s) on a clinical trial, provided that the experimental agent(s) is not a PI3K inhibitor or v-akt murine thymoma viral oncogene homolog 1 (AKT) inhibitor (experiment agent[s] must be discontinued for >= 3 weeks prior to starting study treatment)
Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
Patients who have progressed on initial therapy will not be considered for re-induction treatment
Prior treatment with doxorubicin and/or bevacizumab
Previous assignment to treatment during this study
Patients receiving concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea; however, prior treatment with DNMTi therapy (i.e., decitabine or azacitidine) for MDS or other antecedent hematologic malignancy is allowed\r\n* NOTE: if the patient has been initiated on the protocol defined regimen (i.e. decitabine without a FLT3 inhibitor) before the FLT3 mutation status was known, the patient may be registered on the protocol and start midostaurin on day 11
Treatment naïve patients
Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments
Prior treatment (somatostatin analogs excepted) must be completed at least 2 weeks prior to registration; in addition, prior treatment (somatostatin analogs excepted) must be completed at least 4 weeks prior to initiation of study drug; treatment-related toxicities must have improved to =< grade 1 prior to registration, with the exception of alopecia
Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon
Prior treatment with 5-azacytidine followed immediately by HiDAC and mitoxantrone as proposed in this study (NOTE: prior therapy with 5-azacytidine or decitabine or HiDAC or mitoxantrone would be allowed-in patients with relapsed/refractory disease- unless the prior therapy was identical to the schema/schedule proposed in this study)
Prior treatment with eribulin
Patients may not be receiving Coumadin while on treatment; other anticoagulants are allowed
Subjects may be receiving anti-cancer treatment, but this treatment should be have been instituted at least 4 weeks prior to enrollment, and may not change during the study period
Prior treatment with doxorubicin (doxorubicin hydrochloride) up to 400 mg/m^2
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Previous treatment with chemotherapy (cytarabine, idarubicin, daunorubicin) for a hematological disorder; Exceptions: patients with prior diagnosis of myelodysplastic syndrome (MDS) and/or treatment with hypomethylating agent (azacytidine or decitabine) are not excluded, prior hydroxyurea allowed
Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
Prior treatment with letrozole is allowed
Patients who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment.
There is no limit on the number of prior chemotherapy regimens allowed; any prior treatment (with the exception of lanreotide or octreotide) must be completed at least 4 weeks prior to initiation of treatment
Any systemic anti-cancer treatment out of allowed timelines
Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment
Previous treatment with any HER2-directed therapy, at any time, for any duration
Angina pectoris requiring treatment
Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last treatment with sorafenib.
Prior treatment with trastuzumab emtansine
Prior treatment with bevacizumab
Refractory to or relapsed after at least 1 prior treatment regimen;
Patients with a prior history of grade 4 rash associated with thalidomide treatment
Prior treatment with KW-0761 or vorinostat.
Patient may have any prior therapy allowed aside from having had prior radiotherapy to the treatment site
Patient who has had any prior radiotherapy to the treatment site(s); as in, definitive therapy for lesion of interest; field overlap from previous treatment is permitted at the discretion of the treating investigator
STEP 2 ENROLLMENT AND RANDOMIZATION: treatment to central nervous system lesions, such as the brain or spine (prior to first line systemic therapy), or symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization, in which case the patient would be randomized to treatment of other metastatic sites or the primary sites (based on the disease remaining after first-line treatment); these treated lesions should be counted towards the total number of metastases at the time of enrollment
Patient is eligible for Low-Dose Cytarabine (LDAC) treatment.
Any treatment in a BMS-936558 (Nivolumab) trial
Prior treatment with an anti-angiogenic agent is not an exclusion criterion.
Prior treatment with CYP17 inhibitors or AR antagonists (e.g. abiraterone, TAK-700, ARN-509, ketoconazole*, enzalutamide, or galeterone) - Treatment naïve only
Prior treatment with Alpharadin® (Xofigo®)
Patient has at least 2 years of nilotinib treatment prior to study entry.
Current treatment with nitrates
Treatment with antiandrogens (e.g., bicalutamide, flutamide, or nilutamide) within 4 weeks of enrollment (day 1 visit)
Previous treatment with an anti-CD19 antibody or fragments
Prior treatment with cabozantinib
The subject has received radiation therapy:\r\n* To the thoracic cavity or gastrointestinal tract within 3 months before the first dose of study treatment\r\n* To bone or brain metastasis within 14 days before the first dose of study treatment\r\n* To any other site(s) within 28 days before the first dose of study treatment
The subject has received radionuclide treatment within 6 weeks prior to the first dose of the study treatment
The subject has had treatment with docetaxel for the treatment of metastatic castrate-sensitive prostate cancer within 6 months before the first dose of study treatment
Require immediate treatment for progressive CTCL
Are unable to discontinue current treatment for CTCL due to risk of progression
Within 8 weeks of treatment initiation (day 0), have received treatment with:\r\n* Imiquimod\r\n* Total body electron beam radiation\r\n* Investigational drugs or treatments
Within 2 weeks of treatment initiation (day 0), have received at or adjacent to the target treatment lesions:\r\n* Any surgical procedures other than biopsies related to CTCL diagnosis or follow up\r\n* Any topical treatment other than bland moisturizers (creams, lotions, emollients, etc)
Have other concurrent cutaneous conditions in the treatment area or immediately adjacent to the treatment area that would be exacerbated by resiquimod or interfere with assessments
Prior treatment with Docetaxel
Prior treatment with murine 3F8 is allowed; patients with prior m3F8, hu3F8, monoclonal antibody ch14.18 (ch14.18) or hu14.18 monoclonal antibody (hu14.18) treatment must have human anti-hu3F8 antibody (HAHA) titer =< 1300 enzyme-linked immunosorbent assay (ELISA) units/ml
Prior crenolanib treatment for a non-leukemic indication
Patients must not have prior, current or planned treatment as defined below:\r\n* Previous treatment with > 2 anticancer regimens\r\n* Any prior radiotherapy to the pelvis or abdomen\r\n* Surgery (including open biopsy) within 4 weeks prior to the start of study, or anticipation of the need for major surgery during study treatment\r\n* Minor surgery procedures, within 24 hours prior to the first study treatment\r\n* Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (> 325 mg/day)\r\n* Current or recent treatment with another investigational drug within 30 days of first study treatment dosing or earlier participation in this study\r\n* Chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisolone equivalent), excluding inhaled steroids
Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria
Use previously of intra-articular treatment within 4 weeks prior dosing.
Treatment with BT062 in previous studies
Biological agents (antibodies, immune modulators, cytokines, or vaccines) or radionuclide treatment within 6 weeks of the first dose of study treatment
Prior treatment with cabozantinib
Subjects with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents)
Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen
Prior treatment with eribulin
Prior therapy with pazopanib, gemcitabine or docetaxel; patients who have had prior treatment with gemcitabine or docetaxel for a prior malignancy are eligible if they meet the criteria in exclusion #3 and did not experience significant drug related toxicity
Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), are allowed
Prior treatment with cabozantinib
The participant has received radiation therapy:\r\n* To the thoracic cavity or gastrointestinal tract within 3 months of the first dose of study treatment\r\n* To bone or brain metastasis within 14 days of the first dose of study treatment\r\n* To any other site(s) within 28 days of the first dose of study treatment
Prior bevacizumab as 1st line treatment for GB (if treatment was concluded 12 months prior to enrollment, the patient may be eligible to participate in the trial)
Prior therapies for treatment of HL including involved field radiation therapy or any prior treatment for any malignancy with anthracyclines
Have been informed of other treatment options
Participants who relapsed from their previous treatment(s) but were not refractory to any previous treatment.
Prior treatment with fulvestrant
No prior treatment with bendamustine; prior therapy with gemcitabine is permitted
Currently benefitting from continued treatment and have an acceptable safety profile with GSK2110183 as determined by the investigator following previous treatment with GSK2110183 either as monotherapy or as part of a combination treatment regimen.
Previous treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody or cancer vaccine
Any prior treatment with capecitabine for patients enrolled to cohorts 3a/3b and prior lapatinib for participants on cohort 3a
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as hydroxymethyl glutaryl coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment
Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment; note that muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on LDE225 treatment
Previous treatment with SGN-35 or any other prior anti-cluster of differentiation (CD)30-based antibody therapy
Either no previous trans-hepatic arterial treatment or progressive hepatic metastasis after prior regional treatment with trans-arterial embolization; embolization of hepatic artery with different types of medication will be considered to be one regional treatment
Previous treatment with isolated hepatic perfusion
Only prior cytokine based treatment for metastatic RCC [eg, interferon-alpha (IFN-alpha) or interleukin 2 (IL-2)] as prior therapy is allowed
Radiotherapy prior to initiation of therapy is allowed to a limited area (e.g., palliative treatment for painful bone metastases), if it is not the sole site of disease; subjects must have completed treatment at least one week prior to starting study drugs, and must have recovered from all treatment-related toxicities
Prior treatment with epidermal growth factor receptor targeting small molecules or antibodies.
Cannot have received radionuclide treatment within 6 weeks of first dose of study treatment
Patients who are currently receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with LGH447:
Must be at least 21 days since treatment with chemotherapy, biochemotherapy, surgery, radiation, or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
Prior treatment with an anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody if treatment failure was due to adverse events (AEs); if a subject was discontinued from the prior anti-CTLA-4 treatment due to an AE or serious adverse event (SAE), regardless of the type of event, that discontinuation constitutes an exclusion criterion; if AEs were serious enough to require a subject’s withdrawal from prior treatment, the subject should be excluded from this study
Previous treatment with agents that target the IGF receptor
No prior treatment with cytarabine or clofarabine; prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, filgrastim [G-CSF], sargramostim [GM-CSF], Procrit, Aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient
Patient is willing to have two biopsies while on treatment for correlative studies
Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on sonidegib treatment
Chronic treatment with systemic steroids or another immuno-suppressive agent
Prior treatment with intracystic P-32, intracystic bleomycin or radiosurgery
Previous treatment with radiotherapy to the target lesions
Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
Previous treatment for APL, except tretinoin, which may be given for up to 7 days prior to study entry
For patients with MPN: Ruxolitinib treatment requirements will be waived for patients who have failed this treatment in the past or for whom this treatment is otherwise contraindicated
Prior treatment with approximately 60 Gy of radiotherapy
Prior treatment with radiosurgery
Must have relapsed or refractory disease (refractory is defined as progression during treatment or within 60 days after the completion of treatment) requiring 2nd or 3rd line therapy
Has demonstrated compliance during the parent study with study treatment(s), treatment visit schedules, and the requirements and restrictions listed in the consent form.
Is currently participating in GSK1120212 study and is receiving treatment with GSK1120212.
Is currently receiving clinical benefit as determined by the investigator from previous treatment with GSK1120212 either as monotherapy or as part of a combination treatment regimen.
Women with planned treatment of primary definitive chemoradiation therapy
Women with planned treatment of palliative radiotherapy
Patients who have had prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C); patients must be off treatment with temozolomide for at least 23 days; patients who received non-cytotoxic drug therapy must be off treatment for at least 2 weeks; for patients enrolling in Part 1 or Part 3 AND who have progressed on a prior bevacizumab-containing regimen, patients may continue treatment with bevacizumab 10 mg/kg monotherapy, with last dose of bevacizumab administered no fewer than 14 days from start of plerixafor and bevacizumab; for participants enrolling in Part 1 or Part 3 AND who have progressed on a prior anti-VEGF(R) (other than bevacizumab) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days before receiving plerixafor and bevacizumab; for patients enrolled in Part 2 (surgical substudy) AND who have progressed on a prior bevacizumab or other anti-VEGF(R) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days prior to surgery; NOTE: participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide); for any patient who received prior bevacizumab or an anti-VEGF(R) therapy, patient must NOT have discontinued that treatment regimen due to a treatment-related toxicity
Previous treatment with dacarbazine (DTIC) or TMZ
Prior Navelbine allowed provided Navelbine therapy discontinued >= 12 months from day 1 of treatment under this protocol
Patients requiring treatment with any other systemic glucocorticoid; NOTE: this restriction regarding choice of glucocorticoid does not apply should patient need < 2 week course of glucocorticoid for treatment of non-infectious pneumonitis during study
Prior treatment with treatment doses of capecitabine (prior radio-sensitizing doses of capecitabine are allowed as long as the patient did not progress on capecitabine)
Currently receiving treatment with medication known to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Prior treatment with regorafenib
At least one prior HMTA treatment with either azacitidine or decitabine and subsequent loss of response to HMTA, progression while on HMTA, or no response to HMTA, defined as failure to achieve at least hematologic improvement (HI) after 4 cycles of treatment
Treatment with drugs interacting with S-1, 5-FU, or cisplatin.
Prior treatment with lapatinib or trastuzumab are allowed, provided that the agents have never been given in combination
Patients must have an indication for treatment by 2008 IWCLL Criteria
Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication (not known to affect QT interval) prior to course 1 day 1 (C1D1)
Prior treatment with Lenalidomide permitted if:
Currently has no evidence of progressive disease, as determined by the investigator, following previous treatment with GSK2118436 (either as monotherapy or as part of a combination treatment regimen)
Currently receiving treatment with any prohibited medication(s)
Current treatment on another clinical trial
EXPANSION COHORT ONLY: Current treatment on another clinical trial
Prior treatment with MDV3100
Prior treatment with abiraterone
Prior treatment with ketoconazole
Patients with AML and ALL should have received at least 1 prior treatment regimen and either failed to achieve response or relapsed on treatment
Subject has any underlying conditions, which would contraindicate therapy with study treatment (or allergies to reagents used in this study)
Subjects who have progressed on Bevacizumab treatment
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
Participants may have received radiotherapy for palliative purpose, but must not be experiencing > grade 1 treatment related toxicities, and must have completed treatment > 14 days prior to registration
Prior treatment with HAI FUDR
If a patient has any serious medical problems which may preclude receiving this type of treatment
Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) ?14 days prior to the first dose of study treatment,
a. Indication A - ASPS: Prior treatment with cediranib.
Patients must have achieved PR to primary treatment and not be refractory to prior treatment
Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 3 weeks prior to first administration of study treatment
Patient may have any prior therapy allowed aside from having had prior radiotherapy to the treatment site
Patient who has had any prior radiotherapy to the treatment site(s)
Any radiotherapy within 1 week of starting treatment on protocol
Receiving sirolimus for treatment of chronic GVHD (sirolimus for prophylaxis or treatment of acute GVHD is acceptable).
Prior radiotherapy that would overlap the anticipated study treatment fields
Previous treatment with brentuximab vedotin
There is no limit on the number of prior treatment regimens
Prior treatment with fludarabine or alemtuzumab based regimens.
Patients who were assigned to an axitinib containing treatment arm in a previous clinical trial
Patients may not participate in this trial if the conditions for continuing treatment in the previous AG-013736 protocol are not met
Patients who have demonstrated relapse to 3 or more prior regimens of SM treatment (not including those given for supportive care)
Grade 4 rash due to prior thalidomide treatment
INCLUSION CRITERIA\n\n        PART 1:\n\n          -  confirmed pathologic diagnosis of a solid tumor not curable with available therapies\n             for which neratinib plus capecitabine is a reasonable treatment option.\n\n        PART 2:\n\n          -  confirmed histologically and/or cytologically confirmed diagnosis of breast cancer,\n             metastatic or locally advanced.\n\n          -  erbB-2 gene amplified tumor (FISH or CISH) or erbB-2 overexpression (IHC 3+, or IHC2+\n             with FISH or CISH confirmation), based on local testing, or based on centralized FISH\n             testing prior to day 1.\n\n          -  disease progression on or following at least 1 prior trastuzumab containing treatment\n             regimen (at least 6 weeks) for metastatic or locally advanced disease. (Prior adjuvant\n             trastuzumab is allowed but not required). A 2 week period is required between the last\n             dose of trastuzumab treatment and first dose of the test article.\n\n          -  Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, and/or\n             metastatic disease treatment setting.\n\n        PARTS 1 and 2:\n\n          -  At least 1 measurable lesion as defined by RECIST criteria.\n\n          -  LVEF within institutional range of normal as measured by multi-gated acquisition\n             (MUGA) or echocardiogram (ECHO).\n\n        EXCLUSION CRITERIA\n\n        PART 2:\n\n          -  prior treatment with capecitabine, lapatinib (20 subjects with prior lapatinib\n             exposure will be enrolled) or any erbB-2 targeted agents except trastuzumab. Treatment\n             with erbB-2 targeted therapy must exceed 2 weeks (14 days) in order to be\n             exclusionary.\n\n          -  prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater\n             than 400 mg/m², epirubicin dose of greater than 800 mg/m², or the equivalent dose for\n             other anthracyclines.\n\n        PARTS 1 and 2:\n\n          -  Subjects with bone as the only site of disease.\n\n          -  Active uncontrolled or symptomatic central nervous system (CNS) metastases, as\n             indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects\n             with a history of CNS metastases or cord compression are allowable if they have been\n             considered definitively treated and are off anticonvulsants and steroids for at least\n             4 weeks before the first dose of test article.\n\n          -  Any other cancer within 5 years prior to screening with the exception of adequately\n             treated cervical carcinoma in situ, or adequately treated basal or squamous cell\n             carcinoma of the skin.
Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part 2.
Both naive and previous systemically treated patients are included \r\n* Prior chemotherapy or immunotherapy is permitted\r\n* Prior investigational agents are permitted, however, no prior treatment with targeted therapies directed to c-KIT/PDGFR allowed (e.g., imatinib or sunitinib)\r\n* Limb perfusion allowed\r\n* If radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions
Prior treatment with isotretinoin is allowed because the trial is based on the hypothesis that HDAC inhibition will potentially overcome resistance to retinoids.
Prior treatment with bevacizumab is not allowed.
Patients on previous treatment with carboplatin.
For patients who are Her2 positive and will be treated on the trastuzumab + mDCF cohort, prior trastuzumab treatment is not allowed
Prior cytotoxic or cyclosporin treatment for HLH.
Previous ZD6474 treatment
Prior history of treatment with dasatinib
Prior treatment with Herceptin (Arm B only)
Subject agrees not to participate in another interventional study while on treatment.
Prior treatment with any anti-androgens, including but not limited to, enzalutamide and bicalutamide
Treatment with any of the following hormone replacement therapies, unless discontinued at least 14 days prior to the first dose of study treatment:
Key Inclusion Criteria for Tumor Collection:\n\n          1. Diagnosis or clinical signs of advanced RCC\n\n          2. Scheduled for cytoreductive or partial nephrectomy\n\n        Key Exclusion Criteria for Tumor Collection:\n\n          1. Known inability to undergo sunitinib treatment as currently labeled, due to\n             pre-existing medical conditions\n\n          2. Requirement for systemic chronic immunosuppressive drugs or corticosteroids\n\n          3. Evidence of brain metastases prior to nephrectomy\n\n        Key Inclusion Criteria for Treatment Study:\n\n          1. Advanced disease, histologically assessed as RCC, with predominantly clear cell\n             histology\n\n          2. Metastatic disease (measurable or non-measurable) that can be monitored throughout the\n             course of the study participation per RECIST 1.1\n\n          3. Subjects who are candidates for standard first-line therapy initiating with sunitinib\n\n          4. Time from diagnosis to treatment < 1 year\n\n          5. Karnofsky performance status (KPS) ? 70%\n\n          6. Life expectancy of 6 months or greater\n\n          7. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to\n             Grade ? 1 according to National Cancer Institute Common Terminology Criteria for\n             Adverse Events Version 4.0\n\n          8. Adequate hematologic, renal, hepatic, and coagulation function\n\n          9. Negative serum pregnancy test for female subjects with reproductive potential, and\n             agreement of all male and female subjects of reproductive potential to use a reliable\n             form of contraception during the study and for 12 weeks after the last dose of study\n             drug\n\n         10. Normal ECG or clinically non-significant finding(s) at Screening\n\n         11. Able to abstain from taking prohibited drugs, either prescription or non-prescription,\n             during the treatment phase of the study\n\n         12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory\n             tests, and other study procedures\n\n        Key Exclusion Criteria for Treatment Study:\n\n          1. Prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC,\n             including immunotherapy, chemotherapy, hormonal, or investigational therapy\n\n          2. Prior history of malignancy within the preceding 3 years, except for adequately\n             treated in situ carcinomas or non-melanoma skin cancer, adequately treated early stage\n             breast cancer, superficial bladder cancer, and non-metastatic prostate cancer with a\n             normal PSA\n\n          3. History of or known brain metastases, spinal cord compression, or carcinomatous\n             meningitis, or evidence of brain or leptomeningeal disease\n\n          4. Patients with 4 or more of the following risk factors:\n\n               1. Hgb < LLN\n\n               2. Corrected calcium > 10.0 mg/dL\n\n               3. KPS < 80%\n\n               4. Neutrophils > ULN\n\n               5. Platelets > ULN\n\n          5. Planned or elective surgical treatment post-nephrectomy for the direct management of\n             RCC, within 28 days before Visit 1 (Week 0)\n\n          6. NCI CTCAE Grade 3 hemorrhage < 28 days before Visit 1 (Day 0)\n\n          7. Clinically significant cardiovascular conditions within 3 months prior to\n             Randomization\n\n          8. Significant gastrointestinal abnormalities\n\n          9. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in\n             the normal range with medication\n\n         10. Active autoimmune disease or condition requiring chronic immunosuppressive therapy\n\n         11. Clinically significant infections, including human immunodeficiency virus, syphilis,\n             and active hepatitis B or C\n\n         12. Current treatment with an investigational therapy on another clinical trial\n\n         13. Pregnancy or breastfeeding\n\n         14. Any serious medical condition or illness considered by the investigator to constitute\n             an unwarranted high risk for investigational treatment
Prior treatment with gemcitabine
Patient meets the FDA-approved indication for Atezolizumab treatment in NSCLC.
Prior treatment with investigative androgen receptor (AR) agents
Prior treatment with regorafenib.
Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
Patients who have had previous treatment with topotecan
Prior treatment with any gene therapy product
Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting treatment
Previous treatment with anthracycline antibiotics (e.g. Doxorubicin) or sorafenib.
Treatment with prohibited medications less than or equal to 14 days prior to first day of study treatment
Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication prior to administration of study drug
Prior treatment with temozolomide, dacarbazine or procarbazine.
French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 28 days.
Prior irinotecan treatment.
For subjects receiving neoadjuvant therapy only, time between start of neoadjuvant treatment and randomization must be ? 8 weeks and subjects must be scheduled to undergo definitive treatment (including surgery and/or radiotherapy) with curative intent within approximately 9 months of starting neoadjuvant treatment
Osteoporosis requiring treatment at the time of randomization or treatment considered likely to become necessary within the subsequent six months
Study treatment must begin within 30 days of surgical resection or adjuvant treatment; this timeline may be extended if further time for recovery from treatment related toxicities is required
Willing to undergo or must have had a lower GI biopsy within 7 days of informed consent to confirm GI GvHD. Biopsy results are not needed to initiate treatment; however, if biopsy results are not consistent with aGvHD, treatment with GLASSIA will be discontinued.
Participants must be receiving systemic corticosteroids. Treatment with methylprednisolone/systemic steroids must have been initiated within 72 hours prior to the first dose of study treatment after enrollment
Any prior history of treatment with maytansine (DM1 or DM4)-based ADC
Weekly paclitaxel must be an acceptable treatment option
Prior treatment with antiPD-1, or antiPD-L1 therapeutic antibody or pathway targeting agents
Other concomitant anticancer treatment
Prior treatment with abiraterone acetate
Prior treatment with cabazitaxel
Patients whose tumors have progressed on first-line treatment
Prior treatment with ibrutinib
Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
Use of drugs known to inhibit UDP glycosyltransferase 1 family, polypeptide A1 gene (UGT1A1), such as Atazanavir, Gemfibrozil, Indinavir, or Ketoconazole while on study treatment; (patients using these drugs must not take these drugs on the day study treatment begins and for the duration of study treatment)
Subject is not expected to show a therapeutic response to existing available treatment.
Current treatment on another therapeutic clinical trial
Must have had prior treatment with brentuximab vedotin or not a candidate for treatment with brentuximab vedotin
Completion of at least 1 cycle of treatment with ibrutinib and confirmed evidence of disease progression or refractoriness to treatment or
Discontinuation of ibrutinib treatment at an earlier time due to toxicity
Subjects who progressed after receiving at least 2, but no more than 3, prior SoC treatment lines
Prior treatment with second generation anti-androgens (e.g. abiraterone, enzalutamide)
Treatment with immune modulators including
Must not be taking hydroxychloroquine for treatment or prophylaxis of malaria
In the absence of rapidly progressing disease and after discussion with the Principal Investigator (PI), the interval from prior treatment to time of IMGN901 administration will be at least 2 weeks or at least 5 half-lives for cytotoxic/noncytotoxic agents; for prior monoclonal antibody therapy the interval from prior monoclonal antibody treatment to time of IMGN901 administration will be at least 2 weeks; the use of chemotherapeutic or anti-leukemic agents other than hydroxyurea is not permitted during the study with the exception of intrathecal (IT) therapy for patients with controlled central nervous system (CNS) leukemia at the discretion of the PI; hydroxyurea is allowed prior to the initiation of IMGN901 and during the first 3 cycles, either prior to or concomitantly with IMGN901 administration initially to control leukocytosis
More than one prior treatment regimen for ALL or LL
Prior treatment with pacritinib
Previous treatment with sunitinib.
Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume
For Cohort 3 subjects, prior treatment with hypomethylating agents (eg, azacitidine, decitabine)
Previous treatment with docetaxel.
Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox (CAT-8015, HA22), any pseudomonas-exotoxin-containing compound, or any anti-CD22 directed therapy at any time in the past
Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Subjects must be able to receive outpatient treatment and laboratory monitoring (where specifically indicated) at the institution that administers study drug for the entire treatment period
Prior treatment for glioblastoma or gliosarcoma.
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
Patients receiving treatment with any medications that have the potential to prolong the QT interval who cannot discontinue such treatment or be switched to a different medication prior to starting study drug are excluded from the study entry
Accessible for treatment and follow-up
At least one previous line of treatment for the metastatic disease and the last treatment must have included cetuximab or panitumumab. Documentation of clinical benefit and subsequent progression on cetuximab or panitumumab as the most recent line of treatment is required for patients in the expansion part
Treatment with radiotherapy-response or biological-response modifiers
Inclusion Criteria:\n\n        Donors:\n\n          -  Read, understood and provided written informed consent and willing to comply with all\n             study requirements and procedures\n\n          -  6 out of 6 HLA-matched sibling\n\n          -  Negative test for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C\n\n          -  Both male and female patients of childbearing potential enrolled in this trial must\n             use adequate birth control measures\n\n          -  Subjects should be in generally good health and without significant medical\n             conditions, based upon pre-study medical history, physical examination,\n             electrocardiogram (ECG), chest X- ray, and laboratory tests\n\n          -  Meets all criteria to serve as a mobilized blood cell donor in accordance with all\n             applicable individual Transplant Center criteria\n\n        Recipient:\n\n          -  Read, understood and provided written informed consent and willing to comply with all\n             study requirements and procedures\n\n          -  6 out of 6 HLA-matched sibling\n\n          -  Both male and female patients of childbearing potential enrolled in this trial must\n             use adequate birth control measures\n\n        Diagnosis of one of following:\n\n          -  Acute Myelogenous Leukemia (AML) in 1st remission or beyond\n\n          -  Acute Lymphoblastic Leukemia (ALL) in 1st remission or beyond\n\n          -  Chronic Myelogenous Leukemia (CML)\n\n          -  Chronic Lymphoblastic Leukemia (CLL), relapsing after at least one prior regimen\n\n          -  Myelodysplastic Syndrome (MDS), either intermediate 1,2, or high risk by IPI Scoring\n             System or transfusion dependent\n\n          -  Non-Hodgkins Lymphoma (NHL) or Hodgkins Disease (HD) in 2nd or greater complete\n             remission, partial remission, or in relapse\n\n          -  Meets all criteria to serve as a transplant recipient in accordance with all\n             applicable individual Transplant Center criteria\n\n        Exclusion Criteria:\n\n        Donors:\n\n          -  Unwilling or unable to give informed consent, or unable to comply with the protocol\n             including required follow-up and testing\n\n          -  Prior treatment with any rhuFlt3L product\n\n          -  Any vaccination within 4 weeks prior to CDX-301 dosing\n\n          -  Donation of blood within 8 weeks, or donation of plasma within 2 weeks prior to\n             CDX-301 dosing\n\n          -  Any experimental treatment within 4 weeks prior to CDX-301 dosing\n\n          -  Use of systemic immunosuppressive agents (excluding topical steroids) within 12 months\n             prior to CDX-301 dosing.\n\n          -  History of first degree relatives with primary or secondary immunodeficiency to\n             include type 1 diabetes, multiple sclerosis, rheumatoid arthritis, scleroderma or\n             psoriasis\n\n          -  History of tuberculosis infection\n\n          -  Herpes zoster within 3 months prior to starting study drug\n\n          -  Pregnant or nursing\n\n        Recipient:\n\n          -  Unwilling or unable to give informed consent, or unable to comply with the protocol\n             including required follow-up and testing\n\n          -  Prior allogeneic transplant\n\n          -  More than one prior autologous transplant\n\n          -  Prior treatment with any rhuFlt3L product\n\n          -  Any vaccination within 4 weeks prior to transplant\n\n          -  Uncontrolled infection at the time of the transplant conditioning regimen\n\n          -  Pregnant or nursing\n\n          -  Any condition, which, in the opinion of the clinical investigator, would interfere\n             with the evaluation of the study outcome
The participant may have prior treatment for bladder tumor (excluding radiation therapy) provided that treatment:\r\n* Was completed greater than 30 days prior to the first dose of study agent
Prior treatment with refametinib or regorafenib.
Prior treatment with bortezomib
Any steroid treatment except for that required for replacement therapy in adrenal insufficiency or inhaled steroids for the treatment of asthma
Previous local therapy of any KS-indicator lesion unless the lesion has clearly progressed since treatment; any prior local treatment to indicator lesions regardless of the elapsed time is not allowed unless there is evidence of clear-cut progression of said lesion
Prior treatment with regorafenib.
Prior treatment with an anti-4-1BB antibody
Concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea
Prior treatment with anti-vascular endothelial growth factor (VEGF) drugs other than bevacizumab
Prior treatment with TPI 287
Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1
Systemic drug treatment to induce ovarian suppression if woman is premenopausal
Subject currently participating in a clinical investigation that includes an active treatment arm
Completed at least one cycle of the treatment
Concurrent treatment on another clinical trial; supportive care trials, surgical clinical trials, or non-treatment trials, e.g. quality of life (QOL), are allowed
Documented progression on or after treatment with sorafenib, confirmed by the Investigator upon review of appropriate imaging documentation
Previous treatment with sorafenib for more than 4 weeks during the previous 2 months; prior sorafenib-related toxicity
Must have received the following treatment for glioblastoma: •Prior treatment with radiotherapy and temozolomide; Note: A maximum of two prior chemotherapy/antibody regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted.
Patient must have failed (progressed on or been intolerant of) prior treatment with cabozantinib or vandetanib
Have been informed of other treatment options.
Patients should NOT have had prior therapy for primary myelofibrosis. This includes treatment with cytoreductive drugs (Hydroxyurea), immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), JAK2 inhibitors, or other therapies specifically for myelofibrosis. If they received these classes of drugs for indications other than PMF, treatment should be discontinued at least 6 weeks prior to randomization.
Unable to comply with treatment with the NovoTTF-100A device
The subject has received radiation therapy:\r\n* To the thoracic cavity or gastrointestinal tract within 3 months of the first dose of study treatment\r\n* To bone or brain metastasis within 14 days of the first dose of study treatment\r\n* To any other site(s) within 28 days of the first dose of study treatment
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
For Phase II, Arms 1 and 2, prior cetuximab or other EGFR-targeted antibody therapy is allowed only if administered in the induction setting, or concurrently with radiation in the curative setting, with the last dose of cetuximab administered at least 12 months prior to starting the study treatment. For Arm 3, prior cetuximab must have been administered in the curative, recurrent or metastatic disease setting and disease progression documented within 9 months of the last dose of cetuximab administered in that setting. This regimen (including both platinum and cetuximab) must be the most recent anti-neoplastic treatment regimen administered.
Patients receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti- inflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is also not allowed
Hydroxyurea to control peripheral blood blast count must be discontinued within 24 hours prior to the initiation of treatment; hydroxyurea can also be given through the first cycle of treatment, but should not be initiated earlier than day 5
Any previous treatment with study drug (RO5185426) or participation in a clinical trial that includes RO5185426
Prior treatment with drugs of the immunotoxin class
TREATMENT: Patients who were initially rendered NED by surgical resection must remain NED at the time of treatment
TREATMENT:
ENROLLMENT INTO THE TREATMENT ARMS:
Prior treatment with AN-152
Participants may be treatment naive, refractory to or intolerant of one or more prior therapies, or treated with prior systemic treatment including but not limited to liposomal doxorubicin
Previous local therapy of any KS-indicator lesion unless the lesion has clearly progressed since that local treatment; any prior local treatment to indicator lesions regardless of the elapsed time should not be allowed unless there is evidence of clear-cut progression of said lesion
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of study treatment
Treatment with any approved anti-cancer therapy within 3 weeks prior to the first dose of study treatment
History of prior significant toxicity or intolerance to BCG requiring discontinuation of treatment
Calcium levels must be normalized and maintained within normal limits for study entry and while on treatment
Have received at least one prior course of treatment for ccRCC. Part C only: Prior treatment must include at least 1 course of VEGF-directed therapy.
Received an immune-suppressive based treatment for any reason within 14 days prior to the first dose of study treatment.
For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody (mAb) and for which no other more appropriate treatment option exists, as determined by the investigator
Prior treatment with bicalutamide will not be allowed
Patients may have had treatment for an unlimited number of prior relapses
Prior treatment with albumin-bound paclitaxel or gemcitabine
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
Prior abiraterone treatment completed at least 4 weeks prior to cycle 1 day 1. Participants must have failed prior abiraterone treatment.
Prior treatment with enzalutamide.
Prior systemic treatment with an azole drug (fluconazole, itraconazole) within 4 weeks of cycle 1 day 1.
Serum cholesterol < ULN with or without treatment for hyperlipidemia; if > ULN and untreated, may be rescreened for eligibility after treatment
Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up
All pre-treatment laboratory tests and scans must be performed within 14 days prior to initiation of treatment
Treatment of cGVHD with anti-thymocyte globulins (ATG), or campath within 60 days of screening visit unless used for treatment of acute GVHD
Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-0610. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive myeloma, following discussion with the medical monitor
Lack of treatment with a bisphosphonate or denosumab
Prior treatment with MMB
Patient has had prior treatment with mesenchymal stem cells (MSCs), including remestemcel-L.
Willingness to undergo pre-treatment and on-treatment biopsy.
Prior treatment with TNFRSF agonists.
Prior treatment with more than 3 lines of cytostatic therapies for metastatic disease unless specifically agreed between investigator and sponsor. Subjects with a history of any prior Grade =/> 3 toxicity associated with taxane treatment will be excluded.
Prior treatment with interferon alfa is allowed
Requires initiation of daily PE treatment and has received 1 PE treatment prior to randomization
Patients who are on (or will require) prolonged systemic corticosteroid treatment during the study, except for:
topical applications for treatment of e.g., rash, inhaled sprays for treatment of e.g., obstructive airways diseases, eye drops or local Protocol No. PQR309-003 Protocol Amendment 3, 23 September 2015 PIQUR Therapeutics AG - Confidential Page 15 of 108 injections (e.g., intra-articular);
Previous treatment for MDS or MPN for dose escalation cohorts
Prior treatment with anti-CD70 directed therapy unless CD70 expression is confirmed on tumor tissue obtained after the treatment
Prior treatment with MUC16 targeted therapy (e.g., oregovomab [OvaRex] or abagovomab) including DMUC5754A
Prior treatment with a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC)
Treatment with therapeutic doses of an anticoagulant other than that used for pretreatment of the current (index) VTE episode prior to randomization;
Subject has had prior treatment with cabozantinib
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
Prior treatment with a CD33 antibody
Prior sunitinib treatment.
Prior treatment with mirvetuximab soravtansine
Diagnosis must be confirmed clinically at baseline with 1-2 lesions having been biopsied no sooner than 2 weeks prior to treatment
Currently undergoing treatment with photodynamic therapy, topical chemotherapy agents including imiquimod, fluorouracil, ingenol mebutate (picato) to the selected treatment lesion sites
Previous treatment with brentuximab vedotin or bendamustine.
Radiographic progression, defined by RECIST v.1.1, after the last cancer treatment and within 12 weeks prior to enrollment, compared with scans within 1 year of enrollment.
Subjects must be able to safely be on lithium carbonate treatment for a period of at least four weeks prior to the scheduled prostatectomy
Conditions that could interfere with treatment and procedures
Lack of treatment with a bisphosphonate or denosumab
Prior treatment with ANG1005/GRN1005
NSCLC that has failed crizotinib treatment
Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel
Prior treatment with trastuzumab emtansine, docetaxel, or paclitaxel either as single\n             agents or as part of a treatment regimen.
Prior exposure to experimental treatment targeting either the hepatocyte growth factor (HGF) or Met pathway
Stable brain metastasis (defined as asymptomatic and off steroids ?3 months) are permitted in subjects entering LPT112515 on second-line treatment (completed 12-24 weeks of second-line treatment with trastuzumab plus chemotherapy)
Other investigational agents within 4 weeks prior to study treatment, except for subjects with anaplastic/undifferentiated thyroid cancer who may be enrolled immediately of discontinuation of previous therapy
Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical). -Exceptions: Surgery for melanoma and/or postresection brain radiotherapy (RT) if central nervous system (CNS) metastases and/or prior treatment with adjuvant interferon (IFN) (as described in Exclusion Criterion 2).
The complete set of baseline radiographic images must be available before treatment initiation.
Hematologic growth factors are not allowed at screening or during the first cycle of treatment
Eligible and agreeable for percutaneous biopsy of a primary or metastatic lesion prior to treatment and after approximately 16 weeks of treatment
Prior treatment with trastuzumab, pertuzumab, and T-DM1, either alone or in combination, is required.
Therapeutic anti-coagulative or long term anti-platelet treatment.
Patient must be eligible for treatment with enzalutamide
No previous treatment with chemotherapy for AML, other than hydroxyurea; previous treatment with hypomethylating agents is acceptable
Participants With AML: treatment naive or relapsed for whom experimental therapy is appropriate (as assessed by their treating physician) For Part B:
Subject agrees not to participate in another interventional study while on treatment.
Subject has unavoidable concomitant treatment with any drug known for causing Torsades de Pointes.
Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment.
Previous treatment defined as follows:\r\n* Previous participation in this study\r\n* Previous radiotherapy to the site of vertebroplasty prior to study enrollment\r\n* Samarium therapy at any previous time
Grade 3 (or higher) adverse event assessed as treatment-related at any time during the course of treatment under Protocol 8400-401.
Prior treatment with docetaxel or mogamulizumab;
Requires administration of a prohibited medication or treatment;
Prior treatment with selinexor
Current treatment with steroids
Prior treatment with docetaxel
Prior crenolanib treatment for a non-leukemic indication
Has received prior treatment with ONT-10 or varlilumab, or prior treatment with other MUC1 vaccines or CD27-targeted agents
Previous treatment with azacitidine (any formulation), decitabine, any other hypomethylating agent.
Therapeutic treatment with Coumadin or any other coumarin-derivative anticoagulant
Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment.
Abiraterone acetate; primary resistance to abiraterone will be defined as:\r\n* No PSA decline\r\n* PSA decline less than 50% after 12 weeks of abiraterone therapy\r\n* PSA progression within 12 weeks of abiraterone acetate (AA) treatment (by Prostate Cancer Working Group-2 [PCWG2] criteria), after initial response to therapy\r\n* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone treatment\r\n* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting abiraterone treatment
Enzalutamide; primary resistance to enzalutamide will be defined as:\r\n* No PSA decline\r\n* PSA decline less than 50% after 12 weeks of enzalutamide therapy\r\n* PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria), after initial response to therapy\r\n* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide treatment\r\n* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting enzalutamide treatment
Other second-generation investigational anti-androgen/androgen-receptor targeted therapies, including apalutamide (ARN-509); primary resistance will be defined as:\r\n* No PSA decline\r\n* PSA decline less than 50% after 12 weeks of enzalutamide therapy\r\n* PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria), after initial response to therapy\r\n* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide treatment\r\n* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting enzalutamide treatment
Combination therapy with abiraterone, enzalutamide and/or other second- generation investigational anti-androgen/androgen-receptor targeted therapies, including ARN-509; primary resistance to combination therapy will be defined as:\r\n* No PSA decline\r\n* PSA decline less than 50% after 12 weeks of abiraterone and enzalutamide therapy\r\n* PSA progression within 12 weeks of abiraterone and enzalutamide treatment (by PCWG2 criteria), after initial response to therapy\r\n* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone and enzalutamide treatment\r\n* Unequivocal clinical progression (per the treating provider’s discretion) within 12 weeks of starting abiraterone and enzalutamide treatment
Part A only: For patient who has been treated with afatinib: last treatment at reduced dose below the assigned dose level
Previous treatment with agents targeting the insulin like growth factor (IGF) signalling pathway.
Any prior treatment with topoisomerase I therapy.
Prior treatment with any drugs or therapies that will be administered during the course of this trial including CRLX101, any topoisomerase 1 inhibitor, bevacizumab or the conventional molecularly targeted agent intended for use as standard of care treatment.
Patients must be accessible for treatment and follow up.
Prior treatment with BBI608.
Able to initiate study treatment within 2 weeks of completion of last chemoradiation treatment;
Participants with newly detected enhancement are eligible, with bevacizumab treatment hoped to prevent symptoms
3 months must have elapsed between any prior anti-vascular endothelial growth factor (VEGF) treatment (for example, given as a component of primary treatment) and study participation; these therapies include bevacizumab, cediranib, axitinib, sunitinib as well as other therapeutics targeting VEGF
Previous treatment with nintedanib
Prior treatment with a compound of the same mechanism
Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel, and carboplatin is allowed.
patient had been permanently discontinued from oral dovitinib study treatment, either alone or in combination with fulvestrant, in the parent study
Prior treatment with any agent targeting the hepatocyte growth factor (HGF)/c-Met pathway
Patients who have neuromuscular or muscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are known to cause rhabdomyolysis (such as statins and fibrates), and that cannot be discontinued at least 2 weeks prior to starting LDE225; if it is essential that the patient stays on a statin for hyperlipidemia, only pravastatin may be used with extra caution; patients should not plan to embark on a new strenuous exercise regimen after initiation of study treatment; (nota bene [NB]: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment)
Inclusion Criteria\n\n        Subjects must meet the following criteria to be eligible for study participation:\n\n          1. At least 18 years at the time of signing the informed consent form.\n\n          2. Able to understand and voluntarily sign an informed consent form prior to any\n             study-related assessments/procedures.\n\n          3. Able to adhere to the study visit schedule and other protocol requirements.\n\n          4. Documented diagnosis of multiple myeloma and measurable disease by serum or urine\n             protein electrophoresis (SPEP or UPEP): SPEP ?0.5 g/dL, UPEP ?200 mg/24 hours, or\n             involved serum free light chain (FLC) level ?10 mg/dL provided the serum FLC ratio is\n             abnormal.\n\n          5. Previously received 1 or more lines of anti-myeloma therapy that must have included\n             both lenalidomide and bortezomib (either separately or in combination).\n\n          6. Documented disease progression during or within 60 days after their most recent line\n             of anti myeloma therapy.\n\n          7. Eastern Cooperative Oncology Group (ECOG) performance status score ?2.\n\n          8. All study participants in the USA must be registered into the mandatory POMALYST REMS™\n             (Risk Evaluation & Mitigation Strategy) program, and be willing and able to comply\n             with the requirements of the POMALYST REMS™ program.\n\n          9. All study participants in the USA who are females of child-bearing potential (FCBP)\n             must adhere to the scheduled pregnancy testing as required in the POMALYST REMS™\n             program.\n\n         10. All study participants outside the USA must agree to comply with the POMALYST® PPRMP\n             requirements.\n\n         11. All subjects must be able and agree to take aspirin (81 or 325 mg) daily as\n             prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low\n             molecular weight heparin).\n\n         12. For females of child bearing potential (FCBP): Agree to use 2 reliable forms of\n             contraception simultaneously or practice complete abstinence from heterosexual contact\n             for at least 28 days before starting study treatment, while participating in the study\n             (including dose interruptions), and for at least 28 days after study treatment\n             discontinuation; must follow pregnancy testing requirements as outlined in the\n             POMALYST REMS™ program or the PPRMP.\n\n         13. For all females: Agree to abstain from breastfeeding during study participation and\n             for at least 28 days after study treatment discontinuation.\n\n         14. For all males: Agree to use a latex or synthetic condom during any sexual contact with\n             FCBP while participating in the study and for at least 28 days following\n             discontinuation from study treatment, even if he has undergone a successful vasectomy.\n\n         15. For all males: Agree to refrain from donating semen or sperm while on study and for at\n             least 28 days after discontinuation from study treatment.\n\n         16. Refrain from donating blood while on study treatment and for at least 28 days after\n             discontinuation from study treatment.\n\n         17. Agree not to share medication.\n\n        Exclusion Criteria\n\n        Subjects with any of the following will be excluded from participation in the study:\n\n          1. Peripheral neuropathy Grade ?2.\n\n          2. Non-secretory multiple myeloma.\n\n          3. Any of the following laboratory abnormalities:\n\n               -  ANC <1,000/µL;\n\n               -  Platelet count <50,000/µL for subjects in whom <50% of bone marrow nucleated\n                  cells are plasma cells; or a platelet count <30,000/µL for subjects in whom ?50%\n                  of bone marrow nucleated cells are plasma cells;\n\n               -  Creatinine clearance (CrCL) <45 mL/min as measured directly or as calculated\n                  according to Cockcroft Gault formula;\n\n               -  Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L);\n\n               -  Hemoglobin <8 g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion or\n                  recombinant human erythropoietin use is permitted before study entry);\n\n               -  Serum aspartate aminotransferase (AST) >3.0 x upper limit of normal (ULN);\n\n               -  Serum alanine aminotransferase (ALT) >3.0 x ULN;\n\n               -  Serum total bilirubin >1.5 x ULN (>3.0 x ULN for subjects with known Gilbert's\n                  disease).\n\n          4. Prior history of malignancies, other than MM, unless the subject has been free of the\n             disease for ?5 years. Subjects may be entered earlier than 5 years if they have\n             received curative treatment for the following:\n\n               -  Basal cell carcinoma of the skin;\n\n               -  Squamous cell carcinoma of the skin;\n\n               -  Carcinoma in situ of the cervix;\n\n               -  Carcinoma in situ of the breast;\n\n             Or if they have:\n\n             o Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor,\n             nodes, metastasis] clinical staging system) or non metastatic prostate cancer that is\n             in complete remission or does not require treatment.\n\n          5. Previous therapy with POM and/or MRZ.\n\n          6. History of allergic reaction or hypersensitivity to thalidomide, lenalidomide,\n             bortezomib, carfilzomib, boron, mannitol, or DEX.\n\n          7. Grade ?3 rash during prior thalidomide or lenalidomide therapy.\n\n          8. Gastrointestinal disease that may significantly alter the absorption of POM.\n\n          9. History of the following:\n\n               -  Congestive heart failure of Class III or IV of the New York Heart Association\n                  (NYHA) classification;\n\n               -  Myocardial infarction within 12 months prior to starting study treatment;\n\n               -  Unstable or poorly controlled angina pectoris, including Prinzmetal variant\n                  angina pectoris.\n\n         10. Any of the following within 14 days prior to initiation of study treatment:\n\n               -  Plasmapheresis;\n\n               -  Major surgery (kyphoplasty is not considered major surgery);\n\n               -  Radiation therapy;\n\n               -  Anti-myeloma drug therapy.\n\n         11. Received any investigational agents within 28 days or 5 half-lives (whichever is\n             longer) prior to initiation of study treatment.\n\n         12. Conditions requiring chronic steroid or immunosuppressive treatment (eg, rheumatoid\n             arthritis, multiple sclerosis, or lupus), which likely need additional steroid or\n             immunosuppressive treatments in addition to the study treatment.\n\n         13. Subjects may not receive corticosteroids (>10 mg/day of prednisone or equivalent)\n             within 3 weeks prior to enrollment (use of steroidal inhalation aerosol for asthma is\n             permitted).\n\n         14. Unable or unwilling to undergo antithrombotic prophylactic treatment.\n\n         15. Any condition, including the presence of laboratory abnormalities, which places the\n             subject at unacceptable risk if he/she were to participate in the study, as determined\n             by the Investigator.\n\n         16. Pregnant and/or breastfeeding females.\n\n         17. Known seropositive for or active viral infection with human immunodeficiency virus\n             (HIV).\n\n         18. Known seropositive for or active viral infection with hepatitis B virus (HBV), with\n             the following exceptions:\n\n               -  negative are eligible.\n\n               -  Subjects who had hepatitis B but have received an antiviral treatment and show\n                  non-detectable viral DNA for 6 months are eligible.\n\n               -  Subjects who are seropositive because of hepatitis B virus vaccine are eligible.\n\n         19. Known seropositive for or active viral infection with hepatitis C virus (HCV), with\n             the following exception: Subjects who had hepatitis C but have received an antiviral\n             treatment and show no detectable viral ribonucleic acid (RNA) for 6 months are\n             eligible.
Chemotherapy (except hydroxyurea or emergent use of single-agent cytarabine for cytoreduction), radiotherapy, biologics, and/or other treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug, unless progressive disease is documented; NOTE: hydroxyurea will be allowed during the first cycle of treatment
Prior treatment with a human DR5 agonist.
> 1 prior regimen
Other conditions that could interfere with treatment
Treatment with interferon within 4 weeks prior to first dose of study treatment
Lack of treatment with a bisphosphonate or denosumab
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe.
Willing to undergo pre-treatment lesion biopsy and post-treatment lesion biopsy
Prior treatment with dalantercept or other agent targeting the ALK1 pathway.
Any therapeutic regimen for treatment of recurrent tumor after first line treatment with surgery, radiation and temozolomide.
Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
Subject agrees not to participate in another interventional study while on treatment.
Has >= Grade 2 persistent non-hematological toxicity related to the transplant. Donor lymphocytes infusion (DLI) is not permitted <= 30 days prior to study registration or during the first cycle of treatment on the study in Cohort 1 and first two cycles of the treatment in Cohort 2
Subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
NSCLC that has progressed on prior treatment
Has the subject elected not to undergo treatment with the Gliadel® wafer?
Antimicrobial treatment active against CDAD administered for > 24 hours except for metronidazole treatment failures (MTF)
No other drug treatment for malignant melanoma administered after completing study treatment with trametinib
Treatment with antiarrythmic drugs and any medication known to cause QTc prolongation within 4 weeks before screening and during the study
Prior treatment with Regorafenib
Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab
Known significant dose delays during prior treatment with a taxane due to drug-related toxicities
Treatment with any anti-cancer therapy within 3 weeks prior to initiation of study treatment
Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
Prior treatment with docetaxel for recurrent or advanced NSCLC
Treatment with any anti-cancer therapy within 3 weeks prior to initiation of study treatment
Lack of treatment with a bisphosphonate or denosumab
Prior treatment with docetaxel-containing therapy
Prior vemurafenib treatment
Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes
Any anti-cancer therapy or treatment incorporating chemotherapy, immunotherapy, hormonal therapy, or biologic therapy within 28 days of the start of trial treatment or within 5 times the half life of such treatment, whichever is shorter. Treatment with nitrosoureas or mitomycin C are exceptions to this for which a treatment interval of at least 6 weeks is required
No more than 2 prior regimens are allowed
Previous AML treatment (other than hydroxyurea).
Prior treatment with IL2 within the last 5 years
French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 30 days.
Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel,carboplatin, and gemcitabine is allowed
Participants with NSCLC to be treated with docetaxel need to have received at least one prior anti-cancer treatment regimen in an advanced setting and to have docetaxel be considered appropriate treatment
Prior treatment with cabazitaxel
Part 2 only: Patients may not have had prior treatment with docetaxel.
Prior history of treatment with ABT-263
Patients who have received prior systemic anti-cancer treatment, such as cyclical chemotherapy or biological therapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting study treatment.
Current unstable ventricular arrhythmia requiring treatment
Previous treatment with azacitidine or decitabine
History of treatment with docetaxel in any setting. Participants treated with prior paclitaxel are eligible.
Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the three weeks prior to first dose (unless enrolling on this study after progression Cancer Molecular Analysis Project [CMAP] compassionate use carfilzomib protocol, in which case subject may proceed with current study treatment on next expected date of treatment)
Patients receiving treatment with bupropion.
Prior treatment with AEZS-108.
Application of any topical haemostatic material on the resection surface of the liver prior to application of study treatment.
Inclusion criteria:\n\n        Phase 1 Part (dose escalation): Participants with a histologically confirmed solid tumor\n        including tumors of the central nervous system that was recurrent or refractory and for\n        which no further effective standard treatment was available. All participants must had\n        measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy\n        after evidence of progressive disease post radiation therapy.\n\n        Phase 2 Part (safety and activity): Participants with recurrent or refractory high grade\n        glioma or diffuse intrinsic pontine glioma for whom no further effective therapy was\n        available. All participants must had measurable disease. Participants with diffuse pontine\n        glioma were eligible without a biopsy after evidence of progressive disease post radiation\n        therapy. Participants with a grade III or grade IV glioma must had pathologic confirmation\n        either at the time of initial diagnosis or at the time of recurrence.\n\n        Participants aged ?2 years and ?18 years\n\n        Participants met the body surface area (BSA) requirements to be eligible:\n\n          1. Minimal BSA requirements for a particular dose level;\n\n          2. During the Phase 1 part participants must had a BSA <2.1 m² at the time of enrollment\n\n          3. During the Phase 2 part participants with a BSA ?2.1 m² were eligible, however the\n             actual dose of cabazitaxel for these participants were adjusted to a maximum dose\n             calculated with (capped at) the BSA of 2.1 m²\n\n        Performance status by:\n\n          1. Lansky score ?60 (participants ?10 years of age)\n\n          2. Karnofsky score ?60% (participants >10 years of age) Participants who were unable to\n             walk because of paralysis, but who were mobile in a wheelchair, were considered\n             ambulatory for the purpose of assessing the performance score.\n\n        Participants must had adequate liver, renal and marrow function as defined below:\n\n          1. Total bilirubin ?1.0 x the upper limit of normal (ULN) for age\n\n          2. AST (SGOT) and ALT (SGPT) ?2.5 x ULN\n\n          3. Serum creatinine ?1.5 x ULN for age or creatinine clearance ?60 mL/min/1.73 m²\n\n          4. Absolute neutrophil count ?1.0x10^9 /L\n\n          5. Platelets ?75x10^9/L (transfusion independent)\n\n          6. Hemoglobin ?8.0 g/dL (could be transfused)\n\n        Female participants of child-bearing potential must had a negative pregnancy test ?7 days\n        before starting cabazitaxel treatment.\n\n        Male and female participants of reproductive potential must agreed to use adequate\n        contraception prior to study entry, for the duration of study participation and for 6\n        months following the last dose of cabazitaxel.\n\n        Written informed consent/assent prior to any study-specific procedures. Consent must be\n        obtained from the participant and/or parent(s) or legal guardian(s) and the signature of at\n        least one parent or guardian was required. Investigators also obtained assent of\n        participants according to local, regional or national guidelines.\n\n        Participants must have recovered from the acute toxic effects of all prior therapy to ?\n        grade 1 before entering the study.\n\n        Exclusion criteria:\n\n        Prior treatment within the following timeframes:\n\n          1. Systemic anti-cancer treatment within 3 weeks (6 weeks for nitrosourea, mitomycin and\n             monoclonal antibodies including bevacizumab)\n\n          2. Surgery or smaller field radiation therapy within 4 weeks\n\n          3. Treatment with an investigational agent within 4 weeks or within 5 half-lives of the\n             agent, whichever was longer Craniospinal or other large field radiation therapy\n             (defined as >25% of bone marrow irradiated) within 6 months prior to the first dose.\n\n        Prior systemic radioisotope therapy (this did not include diagnostic imaging or\n        radioimmunoconjugates lacking myelosuppressive properties) or total body irradiation.\n\n        Prior bone marrow or stem cell transplant\n\n        Participants with any clinically significant illness that, in the investigator's opinion,\n        could not be adequately controlled with appropriate therapy, would compromise a\n        participant's ability to tolerate cabazitaxel or result in inability to assess toxicity.\n        This included, but was not limited to uncontrolled intercurrent illness including ongoing\n        or active infection, cardiac disease, renal impairment, planned surgery or psychiatric\n        illness/social situations that would limit compliance with study requirements.\n\n        Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency-syndrome\n        (AIDS)-related disease Known history of hepatitis C or known active hepatitis B infection.\n        Pregnant or breast feeding women Treatment with strong inhibitors or strong inducers of\n        CYP3A4 or enzyme inducing anti-epileptic drugs (EIAED) within 14 days prior to first dose\n        of cabazitaxel and for the duration of study. Non-EIAEDs were permitted.\n\n        Known history of hypersensitivity to taxanes or polysorbate 80 or G-CSF. Participation in\n        another interventional clinical trial and/or concurrent treatment with any investigational\n        drug.\n\n        Participants not able to comply with scheduled visits, treatment plans, laboratory tests,\n        and other study procedures.\n\n        The above information was not intended to contain all considerations relevant to a\n        participant's potential participation in a clinical trial.
Prior treatment with lenalidomide
Patients with a history of prior treatment with ipilimumab
Prior treatment with bortezomib (Velcade) is acceptable with a wash-out of 2 weeks
Participants with GBM can be enrolled 2 weeks after last treatment
Current treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
Any number of prior treatment regimens are allowed
If epidural catheter was used - the catheter must be removed prior to treatment
Prior treatment with investigational drugs that target the human growth factor (HGF) or MET pathway
Subject agrees not to participate in another interventional study while on treatment
Treatment with ritonavir at the time of first dose of study treatment.
Treatment with a cyclical chemotherapy within a period of time that is less than the cycle length used for that treatment prior to first dose of study treatment.
Treatment with any other investigational agents within a period of time that is less than the cycle length used for the treatment or within 28 days (whichever is shorter) prior to first dose of study treatment.
Treatment with prior radiotherapy within 21 days prior to first dose of study treatment; however, if the radiation portal covered ? 10% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy.
Prior treatment with TRC105
Patients with a history of prior treatment with ipilimumab or dasatinib
Local treatment (e.g., surgery, cryotherapy, laser ablation) to any Study Lesion within 4 weeks of initial study treatment
Must have had no previous systemic anti-cancer treatment, though previous loco-regional therapy is allowed: a. Prior treatment with any of the following is allowed: trans-arterial embolization, trans-arterial chemo-embolization, percutaneous ethanol injection, radio-embolization, radio-frequency ablation, or other ablation techniques.
Previous treatment with sorafenib
Completed at least 12 weeks of prior continuous therapy with enzalutamide. A 2 week or less treatment (enzalutamide) holiday will be permitted prior to initiating study treatment.
Prior treatment with floxuridine (FUDR)
The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
Prior treatment with cabozantinib
Prior treatment with HAI floxuridine (FUDR)
If a patient has any serious medical problems which may preclude receiving this type of treatment
Patients must be accessible for treatment and follow-up; investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
In accordance with CCTG policy, protocol treatment is to begin within 3 weeks of patient randomization
Radiotherapy delivered to non-target lesions within one week prior to starting study treatment or delivered to target lesions that will be followed on the study (NOTE: prior sites of radiation will be recorded)
Patient must agree to complete PROs (quality of life [QoL] questionnaire) throughout the study, including after study treatment discontinuation.
Prior treatment with immunomodulators, including toll-like receptor (TLR) agonists, inhibitors of indoleamine 2,3-dioxygenase (IDO)/ tryptophan-2,3-dioxygenase (TDO), or agonists of OX40, is allowed provided that at least 5 half-lives of the drug or a minimum of 3 weeks have elapsed between the last dose of the prior treatment and the proposed Cycle 1, Day 1, with the exception as specified in protocol
Prior treatment with AIs
Hyper sensitivity to fulvestrant treatment excipients
No prior treatment with temsirolimus or an agent specifically targeting met proto-oncogene (c-Met)
Prior treatment with any anti-HER3 (Human Epidermal growth factor Receptor 3) treatment
Concurrent anticancer treatment with any agent other than iniparib and any co-administered chemotherapeutic agent(s) specified on the parental study protocol are not permitted throughout the course of the study.
Previous treatment with vemurafenib
Patients who are on concomitant treatment with drugs that are contraindicated in this study and that cannot be discontinued within the time frames
Patients who are receiving treatment with statins that are known to cause rhabdomyolysis and that cannot be discontinued at least 2 days prior to starting LDE225 treatment
History of prior significant toxicity from a same class of agents as GDC-0575 or gemcitabine requiring discontinuation of treatment
Patients who have received docetaxel plus anti-androgen therapy (ADT) for metastatic castrate sensitive prostate cancer are eligible for the study; (patients may enroll as long as they did not have progressive disease while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1)
Progression on or after endocrine treatment
Previous treatment with fulvestrant
Subjects enrolled into the previously untreated subject cohort must also meet all of the following criteria: No prior treatment for CLL (prior corticosteroid immunosuppression treatment for autoimmune hemolytic anaemia and idiopathic thrombocytopenic purpura (ITP) is permitted); Be considered inappropriate for fludarabine-based therapy for reasons that include, but are not limited to, advanced age or presence of co-morbidities.
Previous treatment with any anti-CD30 antibody
One prior curative regimen (induction, primary or postoperative chemoradiotherapy) should have been given AND all patients should have been exposed to cetuximab as part of prior potentially curative treatment (i.e. with radiotherapy or induction therapy); the last cetuximab dose should be > 3 months
Serum calcium (corrected for serum albumin) or ionized calcium >= lower limit of normal (LLN) (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment)
As per national or local treatment guidelines, endocrine therapy (i.e., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not necessary for participants, at time of entry into the study.
Prior treatment with PM01183.
Have previously been enrolled in Study C0328T03 or CNTO328MCD2001 (either treatment arm)
> 4 weeks since discontinuation of tivozanib treatment on a previous protocol
Prior anti-cancer treatment permitted (with specific criteria)
Patients with either previous vascular endothelial growth factor (VEGF) inhibition based treatment or previous vorinostat based treatment are eligible; however, patients who received both VEGF and histone deacetylase (HDAC) inhibition simultaneously are ineligible
Any number of prior treatment regimens, including treatment naive subjects. Prior treatment with tyrosine kinase inhibitors is permitted.
Prior treatment with pazopanib.
DISEASE CHARACTERISTICS:\n\n          -  Histologically or cytologically confirmed\n\n          -  Locally advanced or metastatic non-hematologic malignancies\n\n          -  Measureable\n\n          -  Refractory to standard therapies or single agent gemcitabine is indicated as a\n             standard treatment option\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No concurrent radiotherapy, chemotherapy, immunotherapy or other investigational\n             agents\n\n          -  Must have recovered from side effects of prior therapies\n\n        PATIENT CHARACTERISTICS:\n\n        Life expectancy\n\n          -  > 12 weeks\n\n        Performance Status\n\n          -  ECOG 0 or 1\n\n        Bone Marrow Reserve\n\n          -  Absolute Neutrophil count (AGC/ANC) ? 1,500/uL\n\n          -  Platelets ? 100,000/uL\n\n          -  Hemoglobin > 9 g/dL\n\n        Renal Function\n\n          -  Calculated Glomerular filtration rate (GFR) > 59mL/min/1.73M^2\n\n        Hepatic Function\n\n          -  Total bilirubin ? 1.5 X ULN\n\n          -  AST, ALT, and ALP ? 3 X ULN or ? 5.0 x ULN, if liver metastasis exists\n\n          -  PT INR ? 1.5 X ULN\n\n        Cardiovascular\n\n          -  No history of clinically significant vascular disease\n\n          -  No New York Heart Association (NYHA) Class > II heart failure\n\n        Hematologic\n\n          -  No history of bleeding disorders\n\n          -  No evidence of bleeding diathesis or coagulopathy\n\n          -  No presence of clinically significant hemoptysis or hematuria, presence of serious\n             non-healing wound or ulceration, or signs of other bleeding\n\n          -  No evidence of a tumor invasion of any major blood vessel\n\n          -  No trauma with increased risk of life-threatening bleeding or history of severe head\n             trauma or intracranial surgery within two months of study entry\n\n        Surgery/Procedures\n\n          -  No major surgery or open biopsy within 28 days before drug infusion or evidence of\n             active bleeding postoperatively\n\n          -  No plan for any major surgery during treatment period\n\n          -  No presence or requirement of an epidural catheter or lumbar puncture within 48 hours\n             prior to each dose of study treatment\n\n          -  No anticipation of receiving an epidural catheter or a lumbar puncture within 48 hours\n             after each dose of study treatment\n\n        Excluded Medications or Treatment Regimens\n\n          -  Unfractionated heparin of > 15,000 units/day within 8 hours prior to each dose of\n             study treatment\n\n          -  Low-molecular weight heparin at a higher dose than recommended for prophylactic used\n             or required within 20 hours prior to each dose of study treatment\n\n          -  Warfarin used or required within 48 hours prior to each dose of study treatment and\n             the prothrombin time (INR) exceeded the upper limit of normal range\n\n          -  Direct thrombin inhibitors or Xa inhibitors\n\n          -  Acetylsalicylic acid used or required within 72 hours prior to each dose of study\n             treatment\n\n          -  Clopidogrel bisulfate used or required within 48 hours prior to each dose of study\n             treatment\n\n          -  Anticipated requirement for anti-platelet or anti-coagulant agents excluding\n             non-aspirin NSAID within 48 hours following study treatment infusion\n\n        Other\n\n          -  No active systemic infection requiring parenteral antibiotic therapy\n\n          -  No history of or presence of a CNS disease\n\n          -  No history of allergic reactions to compounds of similar chemical or biologic\n             composition\n\n          -  Not HIV positive\n\n          -  No women who are pregnant or nursing\n\n          -  A negative serum pregnancy test if female\n\n          -  Patients, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study\n\n          -  No history of significant renal, endocrinologic, metabolic, immunologic or hepatic\n             disease\n\n          -  No evidence of psychiatric illness/social situations\n\n          -  Other illness that in the opinion of the investigator would exclude the patient from\n             participating\n\n          -  Must provide informed consent and HIPAA authorization and comply with\n             protocol-specified procedures and follow-up evaluations
Subjects must have undergone prior treatment with ? 2 treatment lines of anti-myeloma therapy
All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [? partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ? minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
Patients who are currently receiving treatment with QT prolonging medication with a known risk to induce Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
At least two prior treatment regimens for chronic lymphocytic leukaemia.
Any infectious disease requiring treatment at the time of enrolment or within the previous 2 weeks.
Prior treatment with BI 836826.
Previous treatment with ofatumumab.
Part A2: Unable to swallow tablets. Intolerant of therapy with erlotinib. Concomitant treatment with the cytochrome P450 3A (CYP3A) modulators. Must not have received treatment with any of these modulators within 14 days of study treatment.
Treatment with investigational parenteral anti-influenza drugs (IV peramivir, IV zanamivir or IV oseltamivir) in the 4 weeks prior to Baseline.
Prior treatment with lenalidomide or everolimus
Treatment-related MDS
Treatment-related MDS
Previous treatment with ofatumumab.
subject elected not to undergo treatment with Gliadel wafer
Is treatment naive or has received prior treatment for metastatic melanoma.
If previously treated with bortezomib (alone or in combination), progression during treatment
Any progression during treatment if the len/dex combination was the subject's most recent line of therapy
Prior carfilzomib treatment
For patients >= 60 years old: at least one induction chemotherapy treatment or alternative treatment.
In the investigator's opinion and in compliance with the Institution Hematology Tumor Board's guidances, the patient should not be eligible for any additional chemotherapy treatment before the ASCI treatment.
The patient is receiving full dose subcutaneous heparins or is under anti-coagulation treatment.
Current diagnosis for depression, including treatment with an SSRI.
Active diagnosis of psoriasis or currently receiving treatment for psoriasis.
Any patient taking hydroxychloroquine for treatment or prophylaxis of malaria
prior treatment with PF-02341066
current treatment in another clinical trial
Previous treatment with brentuximab vedotin.
Patients may have had treatment (including radiotherapy) for any number of relapses prior to this recurrence
Prior treatment with taxanes or anthracyclines is required;
Concurrent treatment with bisphosphonates is permitted, however treatment must be initiated prior to the first dose of study therapy;
Permanent discontinuation of lapatinib in the previous study due to intolerance or treatment failure.
Treatment with any anticancer therapy (standard or investigational) within 21 days prior to Cycle 1, Day 1 or ongoing adverse events from previous treatment
The patient has received intravenous administration of antibiotics within 2 weeks prior to first study treatment or oral antibiotics within 1 week prior to first study treatment.
Suitable for either treatment regimen.
Inclusion Criteria:\n\n        A subject will be eligible for inclusion in this study only if all of the following\n        criteria apply:\n\n          -  Subjects must have histologically confirmed invasive breast cancer with Stage IV\n             disease at primary diagnosis or at relapse after curative-intent surgery. Where the\n             disease is restricted to a solitary lesion, the neoplastic nature of the lesion should\n             be confirmed by cytology or histology.\n\n          -  Documented amplification of ErbB2 3+ by immunohistochemistry or a positive score\n             (>2.2) by FISH using a local laboratory result (which will be considered sufficient in\n             this study with no further verification by a central laboratory).\n\n          -  Subjects must have received no more than one prior chemotherapeutic regimen in the\n             metastatic setting.\n\n          -  If a taxane had been administered in the neoadjuvant, adjuvant or metastatic setting,\n             progression must have occurred ?12 months after completion of this treatment.\n\n          -  Prior therapy with radiation for this breast cancer population is permitted if it was\n             administered in the neoadjuvant or adjuvant non metastatic setting. Radiotherapy given\n             in the metastatic setting, prior to initiation of study medication, is allowed to a\n             limited area (e.g., palliative therapy and involving less than 25% of bone marrow), if\n             it is not the sole site of disease. Subjects must have completed radiation treatment\n             and recovered from all acute radiation treatment related toxicities (e.g., bone marrow\n             suppression) prior to commencement of combination treatment.\n\n          -  The subject must have received all prior chemotherapy treatment at least 4 weeks prior\n             to enrollment in this study and must have recovered from all related toxicities.\n             Subjects who have received weekly dose of prior chemotherapy e.g. gemcitabine or\n             capecitabine may enroll 2 to 3 weeks after cessation of treatment provided that they\n             have recovered from all related toxicities.\n\n          -  Prior therapy with trastuzumab in the neoadjuvant, adjuvant or metastatic setting is\n             permitted. The subject must have received all prior trastuzumab treatment at least 4\n             weeks prior to enrollment in this study and must have recovered from all related\n             toxicities.\n\n          -  Prior endocrine therapy is permitted in the neoadjuvant or adjuvant or metastatic\n             setting. The subject must have received all prior endocrine treatment at least 1 week\n             prior to enrollment in this study and must have recovered from all related toxicities.\n\n          -  Prior diagnosis of cancer is allowed as long as the subject is free of disease for 5\n             years. Subjects with completely resected basal or squamous cell skin cancer, thyroid\n             cancer or successfully treated cervical carcinoma in-situ will be allowed if it has\n             been 1 year or greater since definitive surgery.\n\n          -  Subjects must have measurable disease, according to Response Evaluation Criteria in\n             Solid Tumors (RECIST) guidelines; defined as at least 1 lesion that can be accurately\n             measured in at least 1 dimension (longest diameter [LD] to be recorded) by mammogram,\n             ultrasound or physical exam [Therasse, 2000].\n\n          -  Subjects with liver metastases or stable chronic liver disease are permitted into the\n             study.\n\n          -  Women ?18 years of age:\n\n          -  Non-child-bearing potential (i.e., women with functioning ovaries who have a current\n             documented tubal ligation or hysterectomy, or women who are postmenopausal); or\n\n          -  Child-bearing potential (i.e., women with functioning ovaries and no documented\n             impairment of oviductal or uterine function that would cause sterility). This category\n             includes women with oligomenorrhoea (severe), women who are perimenopausal and young\n             women who have begun to menstruate. These subjects must provide a negative serum\n             pregnancy test at Screening and agree to 1 of the following:\n\n          -  Complete abstinence from intercourse from 2 weeks prior to administration of the first\n             dose of study medication until 5 days after the final dose of study medication; or\n\n          -  Consistent and correct use of 1 of the following acceptable methods of birth control:\n\n          -  Male partner who is sterile prior to the female subject's entry into the study and is\n             the sole sexual partner for that female subject.\n\n          -  Implants of levonorgestrel.\n\n          -  Injectable progestogen.\n\n          -  Any intrauterine device with a documented failure rate of less than 1% per year.\n\n          -  Oral contraceptives (either combined or progestogen only).\n\n          -  Barrier methods, including diaphragm or condom with a spermicide.\n\n          -  Considered by the Investigator to have a life expectancy of ?6 months.\n\n          -  ECOG Performance Status (PS) of 0 or 1 (Karnofsky ?80%) [Oken, 1982].\n\n          -  Subjects must have normal organ and marrow function as defined in Table 3:\n\n        CONFIDENTIAL UM2007/00382/01 LPT111111 28\n\n          -  Table 3 Baseline Laboratory Values for Adequate Organ Function\n\n          -  Hematologic\n\n          -  Absolute neutrophil count ?1.5 × 10^9/L\n\n          -  Hemoglobin ?9 g/dL\n\n          -  Platelets ?100 × 10^9/L\n\n          -  Hepatic\n\n          -  Serum bilirubin ? upper limit of normal (ULN)\n\n          -  Aspartate aminotransferase and alanine aminotransferase\n\n          -  ?3 × ULN without liver metastases\n\n          -  ?5 × ULN if documented liver metastases\n\n          -  Renal\n\n          -  Serum creatinine ?1.5 mg/dL\n\n          -  OR -\n\n          -  Calculated creatinine clearance ?40 mL/min\n\n          -  Subjects must have a cardiac ejection fraction of >50% as measured by echocardiogram\n             (ECHO) or multigated acquisition scan (MUGA) and within the institutional range of\n             normal.\n\n          -  Subjects with stable central nervous system metastases (stable for at least 3 months)\n             as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) or\n             evidence of leptomeningeal involvement are eligible only if they are not taking\n             steroids or enzyme-inducing anticonvulsants.\n\n          -  Subject must be free of gastrointestinal diseases that impede swallowing and retaining\n             of oral medications.\n\n          -  Signed, informed consent prior to registration.\n\n          -  Bisphosphonate therapy for bone metastases is allowed; however, treatment must be\n             initiated prior to the first dose of study medication. Prophylactic use of\n             bisphosphonates in subjects without bone disease, except for the treatment of\n             osteoporosis, is not permitted.\n\n          -  Subjects whose disease is estrogen receptor + and/or progesterone receptor + or\n             unknown status will only be included in the study if they meet the following criteria:\n\n          -  They have symptomatic visceral disease that requires chemotherapy.\n\n          -  Significant visceral organ tumor burden\n\n          -  The disease is considered by the Investigator to be progressing rapidly or is life\n             threatening.\n\n          -  Subjects who have received prior endocrine therapy and who are no longer benefiting\n             from this therapy.\n\n        Exclusion Criteria:\n\n        A subject will not be eligible for inclusion in this study if any of the following criteria\n        apply:\n\n          -  Subjects who have received more than one prior chemotherapeutic regimen in the\n             metastatic setting\n\n          -  Subjects taking treatment with medications provided in the list of restricted\n             medications and substances in the drug information section for lapatinib are not\n             eligible for the study (Section 5.11.2). This includes human immunodeficiency\n             virus-positive subjects receiving combination anti-retroviral therapy because of\n             possible pharmacokinetic interactions with lapatinib.\n\n          -  Prior treatment with lapatinib.\n\n          -  Concurrent anticancer or concomitant radiotherapy treatment;\n\n          -  Concurrent treatment with prohibited medications (Section 5.11.2);\n\n          -  Use of an investigational drug within 30 days or 5 half-lives, whichever is longer,\n             preceding the first dose of investigational treatment, or, concurrent treatment with\n             an investigational agent or participation in another clinical trial involving\n             investigational agents.\n\n          -  Known history of allergic reactions attributed to compounds of similar chemical or\n             biologic composition to lapatinib or nab-paclitaxel or excipients;\n\n          -  Known history of uncontrolled inter-current illness including, but not limited to,\n             ongoing or active infection, symptomatic congestive heart failure, unstable angina\n             pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social\n             situations that would limit compliance with study requirements.\n\n          -  Have current active hepatic or biliary disease (with exception of patients with\n             Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver\n             disease per investigator assessment)\n\n          -  Concurrent disease or condition that would make the subject inappropriate for study\n             participation or any serious medical disorder that would interfere with the subject's\n             safety.\n\n          -  Pregnant or lactating females at any time during the study (due to the potential\n             teratogenic or abortifacient effects of lapatinib and breastfeeding).\n\n          -  Subjects with diseases affecting gastrointestinal function resulting in an inability\n             to take oral medication, including; malabsorption syndrome, a requirement for iv\n             alimentation, prior surgical procedures affecting absorption e.g. gastric resection\n             and uncontrolled inflammatory bowel disease (e.g., Crohn's, ulcerative colitis).\n\n          -  Peripheral neuropathy of Grade 2 or greater.\n\n          -  Unresolved or unstable, serious toxicity from prior administration of another\n             investigational drug and/or of prior cancer treatment.\n\n          -  History of prior malignancy. However, subjects who have been disease-free for 5 years,\n             or subjects with completely resected basal or squamous cell skin cancer, thyroid\n             cancer or successfully treated cervical carcinoma in situ will be eligible if it has\n             been at least 1 year since definitive surgery.\n\n          -  or rendering of informed consent.\n\n        Other Eligibility Criteria Considerations:\n\n          -  To assess any potential impact on subject eligibility with regard to safety, the\n             Investigator must refer to the following document(s) for detailed information\n             regarding warnings, precautions, contraindications, AEs, and other significant data\n             pertaining to the investigational product(s) being used in this study: Clinical\n             Investigator's Brochure (IB), SPM, and the nab-paclitaxel Product Label.
Likely to continue to need treatment of OIC for the duration of participation in the study.
Prior treatment with alemtuzumab (Campath) or similar agents or procedures that depress blood T cell counts to below 50% of the lower limit of normal.
Patients must be suitable for treatment with lenalidomide & dexamethasone.
The subject has a treatment related serious adverse event that remains unresolved or unstable or had pazopanib permanently stopped in a previous study because of intolerate or because it was unsuccessful in treating your cancer
No prior anti-cancer treatment
At least one target lesion. In patients with prior loco-regional therapy, the target lesion(s) must be located in area(s) outside previous treatment
Failure of prior intravesical treatment(s), one of which must include a course of BCG; failure is defined as evidence of TCC on cystoscopic examination and biopsy or cystoscopic examination and urine cytology at least 6 weeks from completion of last treatment
Previous treatment with talimogene laherparepvec or any other oncolytic virus
Prior treatment with obinutuzumab
Minimum 3 weeks since prior systematic treatment or phototherapy
Prior treatment with an anti-CTLA-4 agent
Subject agrees not to participate in another interventional study while on treatment.
Subject who developed persistent intolerable toxicity to ASP8273 treatment in the parent study.
Patients who have been on a statin other than simvastatin within 2 weeks of starting treatment on current study; these include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, and rosuvastatin; if patient is on statin, will need to stop treatment 2 weeks prior to starting treatment on study
Prophylactic use of hematopoietic growth factors within 1 week prior to starting trial treatment
Previous treatment with lenvatinib mesylate (E7080)
Have been informed of other treatment options
Corticosteroids should not be used as anti-emetic therapy; corticosteroid therapy is not permissible except for the following indications: \r\n* As treatment or prophylaxis for anaphylactic reactions\r\n* As a treatment for symptoms of cytarabine (Ara-C) syndrome (including fever, rash, or conjunctivitis)\r\n* Physiologic replacement stress-dosing as indicated for suspected or confirmed adrenal insufficiency
Currently receiving treatment with any medication that has the potential to prolong the QT interval and the treatment cannot be discontinued or switched to a different medication
Carfilzomib was not part of their most recent therapy for the treatment of MM, and
Did not discontinue carfilzomib treatment because of adverse effects.
Previous treatment with tocilizumab (TCZ)
Patients who have had previous treatment with pazopanib or topotecan
The biopsy confirming diagnosis can be up to 12 weeks prior to registration as long as there is no intervening therapy; note: if patient has had lymphoma treatment since previous biopsy, a biopsy should be repeated
Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
Patients who have failed at least one line of a standard treatment, including bendamustine, fludarabine, ibrutinib, or alemtuzumab and require treatment within 2 years of completion of last treatment regimen or untreated with del17p by fluorescence in-situ hybridization (FISH) (high-risk) who do not have an allogeneic stem cell transplant option
Current treatment with steroids
NOTE: concomitant treatment with ongoing trastuzumab (Herceptin) or other targeted/biologic agents is allowed; concomitant treatment with any other type of chemotherapy or hormonal therapy is not allowed
Plan to be on chemotherapy or other allowable treatment for at least 3 months (minimum 70 days) and be willing to come in for study visits\r\n* The plan for treatment should be for at least 3 months at time of study enrollment; the treatment can stop earlier during the study at the discretion of the physician and patient (e.g., due to progression as noted through imaging, toxicity, or patient preference)
Patients must not co-enroll on other treatment trials
Documented, confirmed OIC defined as less than 3 laxations per week over a 1-week OIC confirmation period at any time during screening and prior to initial treatment period day 1
CHILD: Child has completed cancer treatment and is up to 7 years post-treatment
Patients receiving non-intensive treatment
More than 5 painful lesions, or more than 1 requiring immediate localized treatment
Prior acupuncture treatment within 5 years of enrollment
People who are on long-term (> 1 year) chronic treatment are eligible
Within 0-5 years post-active treatment for initial diagnosis or recurrence
Are receiving, or are likely to receive another intervention for the treatment of fatigue during the study period; (per provider report)
Appropriate for treatment with ADT in the opinion of the treating physician
Ongoing continuous treatment with ibrutinib.
Subject must have completed all assessments in their parent protocol and want to continue treatment with ibrutinib.
Meeting any requirement in the parent protocol to permanently discontinue ibrutinib treatment.
Any previous treatment for vulvar HSIL within 4 weeks prior to screening;
Immunosuppression as a result of underlying illness or treatment;
Patients who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.
Documented investigator-assessed relapse or progression after the last treatment is required if the participant responded and then progressed on the prior treatment.
And for Treatment Period 2 only: 1) Patients participating in Treatment Period 1 must have had disease progression after receiving at least 4 weeks of progestin therapy or 2) Patients must be determined as PrR negative status at Screening.
Prior treatment with selinexor
Participants on bisphosphonates/denosumab may continue receiving bisphosphonate therapy during study treatment
Subject agrees not to participate in another interventional study while on treatment.
Not amenable to treatment with curative intent
Prior treatment with the Optune® system.
Active treatment on another clinical trial.
Agree to undergo a pre-treatment and on treatment biopsy and have disease amenable to biopsy required in PK/pharmacodynamic dose expansion cohorts.
Toxicity from previous anticancer treatment.
Have completed active cancer treatment at least 1 year prior to study enrollment
Patients taking Viagra must have a 1 day washout period prior to treatment.\r\n* Note: patients must agree to discontinue Viagra while on study treatment.
Planned treatment with any VEGF?TKI treatment with treatment has not yet begun
Patients that are between 1-5 years post treatment
Current lymphedema treatment
Patients will be eligible for treatment of multiple synchronous osseous sites only if those sites can be included in no more than three treatment sites; for patients with painful metastases that are contiguous but do not fit into the definition of a site listed above, those patients will still be eligible but will be considered to have two treatment sites; for example, a patient with a lesion of T4, T7 and T9 would be eligible but would be considered as two treatment sites since more than five consecutive vertebral bodies would be treated; these lesions could be treated with one field, even though the treatment is coded as two sites
Treatment plan including autologous HSCT
Requires treatment with non-steroidal anti-inflammatory agents that cannot be stopped for one week during study participation
Subjects who began a medical intervention for treatment of their disease that has a possible impact on pain (including mitogen-activated protein kinase kinase [MEK] trials) will not be eligible until after one year on the medical treatment; at that time, eligibility will be discussed with the PI of the medical study to assess the stability of the patient’s pain and whether further pain-related changes due to the medical treatment are likely
Anytime from treatment
Has initiated treatment as part of an active St. Jude Children's Research Hospital (SJCRH) treatment plan
Pain appeared during or up to 12 weeks after treatment with oxaliplatin, paclitaxel, docetaxel or any combination of these
Current treatment with pregabalin
CIPN that may be associated with previous treatment with a vinca alkaloid (e.g. vincristine, vinblastine), or current treatment with a vinca alkaloid
If sexually active, patients will take contraceptive measures for the duration of protocol treatment and continue until two months after treatment; the effectiveness of hormonal contraceptives containing levonorgestrel has been shown to be reduced by perampanel at a 12 mg dose; therefore, alternative or back-up methods of contraception are recommended
If sexually active, patients will take contraceptive measures for the duration of protocol treatment and continue until one month after treatment; the efficacy of hormonal contraceptives during and for 28 days following the last dose of aprepitant may be reduced; alternative or back-up methods of contraception must be used
If patients are on opioids for the treatment of cancer pain, they must have had no dose changes (> 25%) for at least 48 hours prior to study entry; change in opioid dose after study entry is allowed
Subjects already receiving other treatment for hot flashes.
Post HNC primary treatment
In early survivorship phase, defined as being post-surgery to ending of active treatment to 18 months post active treatment for stage 0-3 breast cancer (BCA)
Patients receiving treatment for an IFI are not eligible
Child: child is in treatment remission and has completed intensive therapy
Patients receiving treatment for an IFI are not eligible
Off-treatment and progression-free for at least 12 months and =< 14 years; treatment cessation is defined as the final dose of chemotherapy, the last dose (fraction) of radiation, or date of surgery, whichever occurred last
Off treatment > 14 years
Previous treatment with low level laser (regardless of indication)
Serum creatinine acceptable for treatment with cisplatin per institutional guidelines
Diabetics requiring insulin treatment
Patient participants must be at a point of treatment initiation/change or evaluation for treatment initiation/change
Prior celiac plexus block, or other neurolytic pain control treatment
Received treatment for breast cancer, and treatment must have been completed at least 2 weeks prior to enrollment in trial, but no longer than 2 years post-treatment
Tried at least 1 prior pharmacological/non-pharmacological treatment for their genitourinary symptoms
Planned continuous antibiotic treatment during RT
If patients are on opioids for the treatment of cancer pain, they must have had no major dose change (> 25%) for at least 48 hours prior to study entry; change in opioid dose after study entry is allowed
Previous assignment to treatment during this study; subjects permanently withdrawn from study participation will not be allowed to re-enter study
Caregivers of patients who are receiving hospice care will be excluded; caregivers who are themselves undergoing active cancer treatment will be excluded (hormonal treatment allowed)
Have treatment with radical prostatectomy or radiation treatment > 3 months prior to enrollment, if receiving these treatments
Completed all primary treatment
Completed initial regional and systemic treatment
CANCER PATIENT GROUP: Currently receiving ADT treatment for at least 6 months (and continue to receive treatment during the duration of the study)
May be receiving maintenance therapy that has a goal of prevention of recurrence but there should be no expectations for further active treatment
Prior visit to a survivorship clinic or previously provided with a treatment summary and care plan
Prior treatment with an oxaliplatin-containing regimen
Prior chemotherapy treatment, including radio-sensitization in pre- and post-operative settings
Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.
Treatment for hyperleukocytosis with hydroxyurea;
Short course systemic corticosteroids is permissible for disease control, improvement of performance status or non-cancer indication if =< 10 days and must be discontinued prior to study treatment
melanoma: at least 1 prior treatment (including immunotherapy).
Pre-treatment with anti-CTLA4 antibodies in combination with any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway.
Other prior malignancy active within the previous 2 years except for local or organ confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study
Prior treatment with either obinutuzumab or ibrutinib
Regional nodal irradiation is part of the treatment plan
Prior treatment with an agent targeting the exportin
Relapsed after or are refractory to at least one prior line of chemotherapy which have not included a taxane (with the exception of Cohort 3 of the Lead-In Phase which will allow the enrollment of subjects with prior treatment with a taxane)
AYA has initial or relapsed cancer diagnosis and is actively on treatment and will continue to be on treatment long enough to complete the intervention and evaluation (4 to 6 weeks)
Subjects must be on current treatment with tamoxifen or an aromatase inhibitor for at least two months prior to study enrollment (defined as the date of consent) and should not be planning to discontinue treatment or to change dose or type of endocrine treatment during the duration of the study
Current or past treatment with fluocinonide cream for vaginal dryness, itching, or dyspareunia
Subjects who have had a venous or arterial embolic event AND who have received anti-coagulant treatment, where both the event and the treatment were within six months of the first Investigational Product administration
Minimum pre-treatment oNCF score >= 70
Patients taking drugs leading to significant QT prolongation must have an ECG prior to each treatment
Known previous treatment failure to erythropoiesis stimulating agents (ESAs) (eg, rHuEPO, darbepoetin alfa).
interested in behavioral sleep treatment
Sexually active prior to cancer treatment (>= 17 on the Sexual Health Inventory For Men?[“SHIM”])
Receiving hormonal treatment
Patient undergoing concomitant treatment for upper extremity lymphedema, or who have received treatment within the last 14 days
Previous acupuncture treatment for any indication within 30 days of enrollment
Radiation oncology and medical oncology consults must deem patient suitable for protocol treatment
Previous laser treatment of telangiectasias
Newly diagnoses or needing a new line of therapy and have not yet made a treatment decision
Post HNC primary treatment
Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment; if it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution\r\n* Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment; NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment
Treatment with amifostine or palifermin (keratinocyte growth factor) during radiotherapy
Previous acupuncture treatment for lymphedema
Currently in treatment for a major psychiatric disorder
Planned cisplatin treatment restricted to the following treatment course criteria:\r\n* Dose: > 50 mg/m^2\r\n* Frequency: every (q)3-q4 weeks\r\n* Cycles: 7 maximum
Previous cisplatin treatment
Previous acupuncture treatment for any indication within 30 days of enrollment
Planned continuous antibiotic treatment during RT
Patient must have completed cancer treatment >= 2 years prior to study enrollment
Receiving treatment for cardiomyopathy or heart failure
Men randomized to the treatment arm should not father a baby while receiving topical treatment during this study; men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment
Subjects scheduled to have > 3 Lumbar Punctures over the course of the study treatment period
Any previous treatment for HCV =< 6 months prior to registration
History of prior ductal carcinoma in situ (DCIS) treated within the past two years; patients completing all treatment for a previous diagnosis of DCIS over two years prior to the current diagnosis are eligible
Previous treatment for lymphedema of either arm.
Previous or current treatment with any insulin regimen other than basal insulin, e.g. prandial or pre-mixed insulin (short term treatment due to intercurrent illness including gestational is allowed at the discretion for the investigator).
Previous or current treatment with GLP-1 receptor agonists (e.g. exenatide, liraglutide).
Not engaged in smoking cessation treatment other than the MD Anderson Cancer Center (MDACC) Tobacco Treatment Program
Current sexually transmitted infection (STI) requiring treatment (women may participate after adequate treatment, at the discretion of the treating provider)
Prior treatment for cervical HSIL\r\n* Note: Cervical scarring that occurs after treatment with cryotherapy or LEEP may impact future visual evaluation of the cervix, making visual inspection with acetic acid (VIA) or colposcopy more challenging
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 6 weeks prior to first administration of study treatment
No prior history of NMSC in the treatment fields
Prior ALT-803
Exposure to cisplatin treatment without intervention
Interested in treatment that might change smoking behavior
Women who are receiving any other concomitant treatment for their DCIS/ADH
Patients on treatment with tamoxifen
Major depressive disorder in the last year requiring treatment
Seeking treatment for smoking cessation
Participants must not be currently receiving or have previously received thiazolidinedione treatment unless sputum atypia or endobronchial dysplasia are documented again after thiazolidinedione treatment and within 12 months of entry
Interested in treatment that might change smoking behavior
SUBJECTS ENROLLED IN THE TREATMENT GROUPS RECEIVING VACCINE ONLY (NOT THE IMIQUIMOD GROUP):
Participants must be willing to take supplemental oral calcium 1000 mg and vitamin D3 1000 IU daily for six months (which will be supplied by the research study) after receiving denosumab treatment or no treatment
Prior or concurrent eczema or other eczemoid skin disorders or active skin condition (acute, chronic, or exfoliative) that disrupts the epidermis; persons with psoriasis are not excluded except in cases of:\r\n* any active lesion\r\n* any active lesion in the previous 6 months that required treatment, either systemic or topical\r\n* any prior episode, at any time, extensive enough or severe enough as to require systemic treatment
TREATMENT GROUP
TREATMENT GROUP
Previous treatment wth any TERT or IL-12 containing therapy, or any other DNA immunotherapy;
As determined by the study investigators or consenting professionals, recent prolonged antibiotic treatment as prevention or suppression of an ongoing infection, where treatment involves gut-perturbing antianaerobic antibiotics
Currently undergoing treatment with photodynamic therapy, topical chemotherapy agents including imiquimod, fluorouracil
Currently being treated or scheduled to have treatment with any systemic or intravesical chemotherapeutic agent during the study
Adequate course of treatment with an injectable hypomethylating agent (azacitidine for injection or decitabine) as the last therapeutic intervention for MDS (MYELODYSPLASTIC SYNDROMES) prior to beginning screening for this study. Adequate is defined as:
having received at least 4 consecutive 6-week treatment cycles with decitabine (3-day regimen) or at least 6 consecutive 4-week treatment cycles with decitabine (5-day regimen), or
having demonstrated inability to tolerate treatment with an injectable hypomethylating agent because of unacceptable drug-related toxicity after at least 3 months of attempted treatment: Three 28-day cycles of azacitidine for injection or decitabine 5-day regimen; two 42-day cycles of decitabine 3-day regimen.
Have the last dose of the prior treatment regimen (injectable HMA (HYPOMETHYLATING AGENT) - azacitidine for injection or decitabine) not more than 16 weeks prior to screening for this study (date of informed consent signature).
No less than 3 weeks between the last dose of the prior treatment regimen (injectable HMA (HYPOMETHYLATING AGENT) - azacitidine for injection or decitabine) and the planned date of first dose of IP (IINVESTIGATIONAL PRODUCT).
Ongoing medically significant adverse events from previous treatment, regardless of the time period
Subjects who received prior treatment or are already receiving everolimus treatment prior to study entry are not eligible.
Systemic anti-cancer treatment with a small molecule therapeutic (other than Ruxolitinib for the Combination arm) other than hydroxyurea less than 2 weeks before the first dose of CPI-0610
Patients may have had treatment for no more than 2 prior relapses
Lenalidomide naïve; relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least one prior line of salvage therapy with no prior exposure to lenalidomide, or double-refractory FL subjects with no prior exposure to lenalidomide (FL-1 cohort)
Subjects with diabetes on active treatment (for subjects treated on CC-223 containing arms only)
Treatment with systemic immunostimulatory agents
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment
Prior treatment with pneumotoxic drugs within past year. If prior therapy in lifetime, then excluded if history of pulmonary toxicities from administration.
No previous radiotherapy or systemic treatment for SCCHN
Radiotherapy treatment prior to the first veledimex dose:
Prior treatment with capecitabine
Prior treatment with any prior gene therapy product
Prior treatment with a drug that targets BCMA on tumor cells or any other bi specific antibody construct or chimeric antigen receptor T cell (CAR-T) infusion for the treatment of multiple myeloma
Previous enrollment or randomization of treatment in the present study
Conditions contraindicated to progesterone treatment.
Major depressive disorder in the last year requiring treatment
Expected use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids used for greater than 14 days, investigational vaccines, interleukins, interferons, growth factors, or IVIG during study followup; hepatitis C co-infected subjects should not enroll in this study if they expect to initiate treatment for hepatitis C (e.g., interferons) during this trial
Patient must be scheduled to receive treatment with a bevacizumab containing chemotherapy regimen; patient can be treated with bevacizumab alone or in combination with other chemotherapies; patient may also be receiving treatment with Optune
Current treatment with bisphosphonates (as of time of enrollment)
Current treatment with the anticonvulsant depakote (at time of enrollment)
There will be no restrictions on prior treatment
Radical prostatectomy as definitive treatment for PCa
Prior treatment with alpha radiation therapy (Radium Ra 223 chloride; Xofigo™) during the previous 60 days
Prior endoscopic treatment for BE
Treatment plan for HDC-ASCT
Participants whose clinical care plan includes treatment with anti-angiogenic treatment-based therapy
Patients who are planning to undergo treatment in a different institution
PATIENT: Patients with other primary cancers requiring systemic treatment
Recipients of more than minimal anti-leukemia treatment, with minimal treatment defined as: leukapheresis, hydroxyurea, or cytarabine more than 1 g per square meter
Prior treatment with anti-GD2 monoclonal antibody is permitted only if human anti-human antibody titer is =< 1300 assay developed by Dr. Nai-Kong Cheung
Prior and current therapy:\r\n* For NF1 related benign tumor manifestations there is no standard effective medical treatment, and surgery is the only standard treatment; chemotherapy and radiation therapy are additional treatment options for malignant NF1 related tumors; for the purpose of this study subjects who have not previously received medical or surgical treatment, patients who have previously received medical or surgical treatment, and subjects who are currently receiving medical treatment and or radiation for a NF1 related manifestation will be eligible\r\n* Patients must be recovered from acute toxicities of prior therapy in order to be able to safely undergo biopsies proposed on the trial; prior and current treatment for NF1 related manifestations will be recorded on protocol 08-C-0079\r\n* Prior radiation therapy and chemotherapy in patients with MPNST must not have been administered within 4 weeks prior to enrollment
No prior treatment for this diagnosis of NSCLC
Subjects may be enrolled at any point in diagnosis or treatment
Plan to receive dental treatment during the study dates
Previous or on-going radioactive iodine treatment.
Patients must be selected for an endocrine targeted therapy regimen for treatment of their breast cancer by the referring oncologist; selected treatments may be part of experimental treatment protocols for which the patient would be separately consented
Planned total mastectomy for treatment
Patients with other primary cancers requiring systemic treatment.
Patients with other primary cancers requiring systemic treatment
Allowable type and amount of prior therapy: patients with newly diagnosed malignancies should not have initiated treatment for their disease before participating in this study; patients with recurrent or second malignancies may have had prior therapy as appropriate for their disease, but should have completed all prior treatment at least 30 days before participation in this study and should not have initiated new treatment for the current problem
Participants undergoing active treatment, or who have completed treatment, will have radiographic abnormalities that may or may not be recurrent tumor
Prior treatment
Patients that may need dose reduction to commence cycle 1 treatment
Prior treatment with cetuximab with tumor progression during or within 6 months after completing treatment.
Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents.
Prior treatment with CD47 or signal regulatory protein alpha (SIRP?) targeting agents (with exception of Hu5F9-G4 for patients in the Rollover cohort).
Treatment-naïve/Unfit Cohorts Only: Any prior anti-leukemic therapy (excluding hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low dose cytarabine.
Unresolved chronic toxicity of previous AML treatment
With relapsed or refractory AML (hydroxyurea is not considered a prior treatment regimen) OR with treatment-naive AML who decline intensive induction chemotherapy or who are unfit due to co-morbidity or other factors OR with MDS and >= 10% myeloblasts in the bone marrow
Prior treatment with a hypomethylating agent (including but not limited to azacitidine or decitabine), unless last treatment with hypomethylating agent was > 3 months prior to start of protocol treatment OR has received =< 2 cycles of hypomethylating agent without disease progression during those =< 2 cycles and last dose was not within 14 days of first protocol treatment
Prior treatment with SL-401
At least 1, but no more than 5, prior treatment regimens for MCL
Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed, provided all of the following criteria are met: Best response achieved with prior bortezomib at any time was ? PR and with the last PI (PI therapy (alone or in combination) was ? PR, AND Participant did not discontinue bortezomib due to ? Grade 3 related toxicity, AND Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment.
Requires prohibited treatment (i.e., non-protocol specified anticancer pharmacotherapy, surgery or conventional radiotherapy for treatment of malignant tumor).
Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS, MDS/MPN, CMML or AML within 14 days of the first day of study drug treatment
Actively breastfeeding women unless it is interrupted during treatment and at least 6 weeks after treatment discontinuation
Subject agrees not to participate in another interventional study while on treatment.
The patient agrees to follow-up examinations out to 5-years post-treatment
Patients with other primary cancers requiring systemic treatment
TREATMENT GROUP: Elect to undergo, but have not yet started tamoxifen therapy
TREATMENT GROUP: Willing to avoid oral contraception use (which is not recommended while on tamoxifen treatment) for the duration of the study participation
Subjects must be planned for treatment with approved treatment doses of a VEGF receptor TKI (e.g., sunitinib, pazopanib, cabozantinib, axitinib, sorafenib, lenvatinib)
Prior treatment with a VEGF receptor TKI within a time period equivalent to 5 half-lives of the prior TKI (e.g., there should be no substantial amount of TKI remaining in the patient)
Patient undergoing current or recent treatment within past 6 weeks or scheduled for any treatment that could results in changes of lesion appearance between the two study examinations. This would include, but not restricted to, the following: current or recent radiation therapy, surgery, starting or recent chemotherapy.
Prior treatment with alpha radiation therapy (Radium Ra 223 chloride; Xofigo™) during the previous 60 days
Previous brachytherapy treatment will have occurred at least 2 years in the past
Patients 18 years of age and older who are being evaluated for and/or treated for cancer at the NIH Clinical Center or at participating sites:\r\n* Who have a newly diagnosed malignancy for which they have not yet received treatment, or\r\n* Who have a previously treated malignancy that is now recurrent or currently progressing on treatment indicated by:\r\n** Radiographic evidence of tumor growth and/or new metastases, or\r\n** Documented evidence by the treating physician of signs/symptoms of clinical disease progression, or\r\n* Who are currently undergoing treatment (adjuvant, neoadjuvant, etc.), are within the first two (2) cycles of treatment, and for whom disease response has not yet been assessed\r\n** In this circumstance, specimen collection should occur as distant in time from the most recent drug administration as possible such as after completion of a treatment cycle and immediately prior to initiation of the next cycle\r\n* For matched pair collections only (tissue + blood), patients with ongoing partial response (PR) or stable disease (SD) are eligible\r\n** Confirmation of viable malignancy and/or < 90% tumor necrosis must be confirmed to the coordinating site, as indicated in the final pathology report, for patients enrolled with PR or SD
Prior treatment with sipuleucel-T
Have a diagnosis of any type of NHL and =< 5 years from the last treatment
No treatment with systemic anti-cancer treatment (chemotherapy or biologics) within 2 weeks of starting interferon gamma
Current treatment with steroids (must be discontinued 1 week before starting IFN gamma)
Receiving induction treatment while hospitalized
Prior treatment with MORAb-009
Prior treatment with SS1(dsFv)PE38 (SS1P)
Prior treatment with trabectedin
Eligible for treatment with paclitaxel, doxorubicin and cyclophosphamide
Serum albumin must be planned to be collected after admission, but prior to treatment
Patients who underwent, currently undergoing or planned to start radiation treatment with curative, adjuvant or palliative intent, who have not yet had their first post-treatment visit
Ongoing or prior treatment with traditional disease-modifying anti-rheumatic drugs or biologic agents (RCT)
Have not had their initial doctor consultation to discuss treatment options
Must be candidates to receive endocrine therapy and palbociclib or ribociclib as first-line treatment for their advanced disease. Patients will be considered eligible for study enrollment if they have started on treatment with a standard dose and schedule of palbociclib or ribociclib and endocrine therapy (aromatase inhibitor or fulvestrant) as long as they have not started palbociclib or ribociclib treatment for longer than 4 weeks from time of study enrollment, have sufficient tissue to perform the proposed tissue analysis and must meet all other eligibility criteria. Endocrine therapy can be initiated up to 4 weeks prior to starting palbociclib or ribociclib.
Prior treatment with oxaliplatin.
Prior treatment with PM060184.
Ipilimumab-treated patients must be receiving treatment for the indication(s)\n             approved in their country of residence or where they are receiving treatment
Subjects with prior treatment with a mechanistic target of rapamycin (mTOR) are eligible
WOCBP must agree to follow instructions for method(s) of contraception at the restart of treatment with study drug (dasatinib) and for the duration treatment plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion
Sexually active subjects or their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec/placebo.
current enrollment in a smoking cessation treatment study
For inclusion in the study patient should fulfil the following criteria:\n\n        1. Male or female, aged at least 18 years. 2. Histological or cytological confirmation\n        diagnosis of NSCLC. 3. Radiological documentation of disease progression while on a\n        previous continuous treatment with an EGFR TKI, eg gefitinib, erlotinib or afatinib. In\n        addition, other lines of therapy may have been given. All patients must have documented\n        radiological progression on the last treatment administered prior to enrolling in the\n        study.\n\n        4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR\n        TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).\n\n        5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration\n        over the previous 2 weeks (Appendix G).\n\n        6. Patients must have a life expectancy of ?12 weeks as estimated at the time of screening.\n\n        7. Females should be using adequate contraceptive measures and must have a negative\n        pregnancy test prior to start of dosing if of child-bearing potential, or must have\n        evidence of non-child-bearing potential by fulfilling one of the following criteria at\n        screening: Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least\n        12 months following cessation of all exogenous hormonal treatments. Women under 50 years\n        old would be considered post-menopausal if they have been amenorrhoeic for 12 months or\n        more following cessation of exogenous hormonal treatments and with LH and FSH levels in the\n        post-menopausal range for the institution. Documentation of irreversible surgical\n        sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not\n        tubal ligation.\n\n        8. Male patients should be willing to use barrier contraception, ie, condoms, until 6\n        months after last study drug is taken.\n\n        9. Contact lens wearers must be prepared to not wear contact lenses and wear glasses for\n        the duration of the rifampicin dosing.\n\n          1. Participation in another clinical study with an IP during the last 14 days (or a\n             longer period depending on the defined characteristics of the agents used).\n\n          2. Treatment with any of the following: Treatment with an EGFR TKI (eg, erlotinib or\n             gefitinib) w/in 8 days or approx. 5 x half-life, whichever is the longer, of the first\n             dose of study treatment; any cytotoxic chemo, investigational agents or other\n             anticancer drugs from a previous treatment regimen w/in 14 days of the first dose of\n             study treatment; major surgery (excluding placement of vascular access) w/in 4 weeks\n             of the first dose of study treatment; radiotherapy with a limited field of radiation\n             for palliation w/in 1 week of the first dose of study treatment, with the exception of\n             patients receiving radiation to more than 30% of bone marrow or with a wide field of\n             radiation which must be completed w/in 4 weeks of the first; patients currently\n             receiving (or unable to stop use prior to receiving the first dose) medications or\n             herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and\n             potent inducers of CYP3A4 (at least 3 week prior). All patients must avoid concomitant\n             use of any medications, herbal supplements and/or ingestion of foods with known\n             inducer/inhibitory effects on CYP3A4.\n\n          3. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of\n             starting study treatment with the exception of alopecia and Grade 2, prior\n             platinum-therapy related neuropathy.\n\n          4. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,\n             or other products containing grapefruit or Seville oranges within 7 days of the first\n             administration of the IP until the final PK sample collection on Day 78 of Part A.\n\n          5. Spinal cord compression or brain metastases unless asymptomatic, stable and not\n             requiring steroids for at least 4 weeks prior to start of study treatment.\n\n          6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled\n             hypertension and active bleeding diatheses, which in the Investigator's opinion makes\n             it undesirable for the patient to participate in the study or which would jeopardise\n             compliance with the protocol, or active infection including hepatitis B, hepatitis C\n             and HIV. Screening for chronic conditions is not required.\n\n          7. Inadequate bone marrow reserve or organ function as demonstrated by any of the\n             following laboratory values: ANC <1.5 x 10^9/L; Platelet count <100 x 10^9/L;\n             Haemoglobin <90 g/L; ALT >2.5 times the ULN if no demonstrable liver metastases or >5\n             times ULN in the presence of liver metastases; AST >2.5 times ULN if no demonstrable\n             liver metastases or >5 times ULN in the presence of liver metastases; Total bilirubin\n             >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented\n             Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases; creatinine\n             >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated\n             by Cockcroft and Gault equation); confirmation of creatinine clearance is only\n             required when creatinine is >1.5 times ULN.\n\n          8. Any of the following cardiac criteria: Mean resting corrected QT interval corrected\n             for heart rate using Fridericia's correction factor (QTcF) >470 msec obtained from 3\n             electrocardiograms (ECGs); any clinically important abnormalities in rhythm,\n             conduction or morphology of resting ECG eg, complete left bundle branch block, third\n             degree heart block, second degree heart block, PR interval >250 msec; any factors that\n             increase the risk of QTc prolongation or risk of arrhythmic events such as heart\n             failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome\n             or unexplained sudden death under 40 years of age or any concomitant medication known\n             to prolong the QT interval.\n\n          9. Patients unable to swallow oral medication or patients with GI disorders or\n             significant GI resection likely to interfere with the absorption of AZD9291.\n\n         10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required\n             steroid treatment, or any evidence of clinically active ILD.\n\n         11. Women who are breastfeeding.\n\n         12. Patients with a known hypersensitivity to AZD9291 or rifampicin or any of the\n             excipients of the products.\n\n         13. Concomitant medication contraindicated for use with rifampicin (including, but not\n             limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide,\n             triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A\n             (HMG-CoA)-reductase inhibitors metabolised by CYP3A4, such as lovastatin and\n             simvastatin, ergot alkaloids metabolised by CYP3A4, such as dihydroergotamine,\n             ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine).\n\n         14. For optional genetic research: .Previous allogenic bone marrow transplant or\n             Non-leukocyte depleted whole blood transfusion within 120 days of the date of the\n             genetic sample collection.
For inclusion in the study, patients should fulfil the following criteria:\n\n          1. Male or female, aged at least 18 years.\n\n          2. Histological or cytological confirmation diagnosis of NSCLC.\n\n          3. Radiological documentation of disease progression while on a previous continuous\n             treatment with an EGFR TKI, eg, gefitinib or erlotinib. In addition, other lines of\n             therapy may have been given. All patients must have documented radiological\n             progression on the last treatment administered prior to enrolling in the study.\n\n          4. Confirmation that the tumour harbours an EGFR mutation known to be associated with\n             EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).\n\n          5. ECOG performance status 0-1 with no deterioration over the previous 2 weeks.\n\n          6. Patients must have a life expectancy of ?12 weeks as estimated at the time of\n             screening.\n\n          7. Evidence of non-childbearing status for women of childbearing potential, or\n             post-menopausal status: negative urine or serum pregnancy test within 28 days of study\n             treatment, confirmed prior to treatment on Day 1 of Part A, or post menopausal status.\n             Females should be using adequate contraceptive measures and must have a negative\n             pregnancy test prior to start of dosing if of child-bearing potential or must have\n             evidence of non-child-bearing potential by fulfilling one of the following criteria at\n             screening: post-menopausal defined as aged more than 50 years and amenorrhoeic for at\n             least 12 months following cessation of all exogenous hormonal treatments; women under\n             50 years old would be consider postmenopausal if they have been amenorrhoeic for 12\n             months or more following cessation of exogenous hormonal treatments and with LH and\n             FSH levels in the post-menopausal range for the institution; documentation of\n             irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or\n             bilateral salpingectomy but not tubal ligation.\n\n          8. Male patients should be willing to use barrier contraception, ie, condoms, until 6\n             months after last study drug is taken.\n\n        Patients should not enter the study if any of the following exclusion criteria are\n        fulfilled:\n\n          1. Participation in another clinical study with an IP during the last 14 days (or a\n             longer period depending on the defined characteristics of the agents used).\n\n          2. Treatment with any of the following: Treatment with an EGFR TKI w/in 8 days or\n             approximately 5x half-life, whichever is the longer, of the first dose of study\n             treatment; Any cytotoxic chemotherapy, investigational agents or other anticancer\n             drugs w/in 14 days of the first dose of study treatment; Major surgery (excluding\n             placement of vascular access) within 4 weeks of the first dose; Radiotherapy with a\n             limited field of radiation for palliation within 1 week of the first dose of study\n             treatment, with the exception of patients receiving radiation to more than 30% of the\n             bone marrow or with a wide field of radiation which must be completed within 4 weeks\n             of the first dose of study treatment; Patients currently receiving (or unable to stop\n             use prior to receiving the first dose of study treatment) medications or herbal\n             supplements known to be potent inhibitors of CYP2C8 and of CYP3A4 (at least 1 week\n             prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must try to\n             avoid concomitant use of any medications, herbal supplements and/or ingestion of foods\n             with known inducer/inhibitory effects on CYP3A4, CYP2C8, and/ or CYP1A2.\n\n          3. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of\n             starting study treatment with the exception of alopecia and Grade 2, prior\n             platinum-therapy related neuropathy.\n\n          4. Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,\n             or other products containing grapefruit or Seville oranges within 7 days of the first\n             administration of the IP until the end of Part A.\n\n          5. Spinal cord compression or brain metastases unless asymptomatic, stable and not\n             requiring steroids for at least 4 weeks prior to start of study treatment.\n\n          6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled\n             hypertension and active bleeding diatheses, which in the Investigator's opinion makes\n             it undesirable for the patient to participate in the study or which would jeopardise\n             compliance with the protocol, or active infection including hepatitis B, hepatitis C\n             and human immunodeficiency virus (HIV). Screening for chronic conditions is not\n             required.\n\n          7. Inadequate bone marrow reserve or organ function as demonstrated by any of the\n             following laboratory values: ANC <1.5 x 10^9/L; Platelet count <100 x 10^9/L;\n             Haemoglobin <90 g/L; ALT >2.5 x the institutional ULN if no demonstrable liver\n             metastases or >5 x institutional ULN in the presence of liver metastases; AST >2.5 x\n             institutional ULN if no demonstrable liver metastases or >5 x institutional ULN in the\n             presence of liver metastases; Total bilirubin >1.5 x institutional ULN if no liver\n             metastases or >3 x institutional ULN in the presence of documented Gilbert's Syndrome\n             or liver metastases; Creatinine >1.5 x institutional ULN concurrent with creatinine\n             clearance <50 mL/min (measured or calculated by Cockcroft-Gault formula); confirmation\n             of creatinine clearance is only required when creatinine is >1.5 x institutional ULN.\n\n          8. Any of the following cardiac criteria: Mean resting corrected QT interval corrected\n             for heart rate using Fridericia's correction factor (QTcF) >450 msec obtained from 3\n             ECGs; Any clinically important abnormalities in rhythm, conduction or morphology of\n             resting ECG eg, complete left bundle branch block, third degree heart block, second\n             degree heart block, PR interval >250 msec; Any factors that increase the risk of QTc\n             prolongation or risk of arrhythmic events such as heart failure, hypokalaemia,\n             congenital long QT syndrome, family history of long QT syndrome or unexplained sudden\n             death under 40 years of age or any concomitant medication known to prolong the QT\n             interval.\n\n          9. Patients unable to swallow oral medication or patients with GI disorders or\n             significant GI resection likely to interfere with the absorption of AZD9291.\n\n         10. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation\n             pneumonitis which required steroid treatment, or any evidence of clinically active\n             ILD.\n\n         11. Women who are breastfeeding.\n\n         12. Patients with a known hypersensitivity to AZD9291 or itranconazole or any of their\n             excipients.\n\n        12. Concomitant medication contraindicated for use with itraconazole (including, but not\n        limited to): cisapride, oral midazolam, nisoldipine, pimozide, quinidine, dofetilide,\n        triazolam, levacetylmethadol (levomethadyl), 3-hydroxy-3-methyl-glutaryl coenzyme A\n        (HMG-CoA)- reductase inhibitors metabolized by CYP3A4, such as lovastatin and simvastatin,\n        ergot alkaloids metabolized by CYP3A4, such as dihydroergotamine, ergometrine (ergonovine),\n        ergotamine and methylergometrine (methylergonovine).\n\n        13. For optional genetic research: Previous allogenic bone marrow transplant or\n        non-leukocyte depleted whole blood transfusion within 120 days of sample collection.
Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotinib treatment prior to pre-screening at approved total dialy dose of 600 mg BID or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis
Previous treatment with alpha-interferon of any duration
Prior treatment with BLZ-100.
Inclusion criteria:\n\n        In the dose escalation part: patients with high MET tumor expression, evaluable or\n        measurable solid tumors for which no standard therapy is available.\n\n        In the expansion cohorts: in the first cohort, patients with diagnosed MET gene amplified\n        including NSCLC patients and measurable tumors for which no standard therapy is available\n        will be eligible. In the second cohort, patients with advanced P-MET positive measurable\n        solid tumor without MET- gene amplification for which no standard therapy is available will\n        be eligible.\n\n        Exclusion criteria:\n\n        Patient less than 18 years old. ECOG performance status >2. Any serious active disease or\n        co-morbid condition, which, in the opinion of the Investigator, may interfere with the\n        safety or the compliance with the study.\n\n        Poor bone marrow reserve as defined by absolute neutrophil count <1.5 x 10^9/L or platelets\n        <100 x 10^9/L.\n\n        Poor organ function as defined by one of the following:\n\n          -  Total bilirubin >1.5 x ULN\n\n          -  AST, ALT, alkaline phosphatase >2.5 x ULN or >5 x ULN in case of documented liver\n             metastasis. Alkaline phosphatase up to 5 x ULN in case of osteolytic bone metastasis\n             without liver metastases is allowed\n\n          -  Serum creatinine >1.5 x ULN or\n\n          -  Serum creatinine between 1.0 and 1.5 x ULN associated with calculated creatinine\n             clearance <60 mL/min\n\n          -  Proteinuria >500 mg/24H Pregnant or breast-feeding women. No use of effective birth\n             control methods, when applicable. No measurable or evaluable tumor lesion in the Dose\n             Escalation part, and no measurable lesions in the expansion cohorts.\n\n        Brain metastasis (other than totally resected or previously pre-irradiated and no\n        progressive/relapsing) or lepto-meningeal carcinomatosis.\n\n        No resolution of any specific toxicities (excluding alopecia) related to any prior\n        anti-cancer therapy to grade ?1 according to the NCI CTCAE v.4.03.\n\n        Wash out period of less than 3 weeks from previous antitumor therapy or any investigational\n        treatment (and less than 6 weeks in case of prior nitroso-urea and or mitomycin C\n        treatment).\n\n        Any surgery with major risk of bleeding performed less than 10 days prior to study\n        treatment administration.\n\n        Any other severe underlying medical conditions, which could impair the ability to\n        participate in the study or the interpretation of its results.\n\n        Patients treated with potent CYP3A inhibitor unless it can be discontinued at least 2 weeks\n        prior to study treatment or 5 elimination half-life, whichever is the longest.\n\n        Patients treated with potent and moderate CYP3A inducers unless it can be discontinued at\n        least 2 weeks prior to study treatment or 5 elimination half-life, whichever is the\n        longest. Patients treated with weak CYP3A inducers such as dexamethasone are eligible.\n\n        Known hypersensitivity or any adverse event related to the study drug excipient.\n\n        Prior treatment with any compound in the same class. Mean QTc interval prolongation.\n\n        The above information is not intended to contain all considerations relevant to a patient's\n        potential participation in a clinical trial.
Patients who are not candidates for RT treatment
Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. There is no limit to the number of prior treatment regimens.
Participants with second/other active cancers requiring current treatment
For Concomitant Treatment: No prior treatment with MRZ or any other PIs, including BTZ, carfilzomib (CFZ), or ixazomib (IXZ)
Indication of systemic treatment for the relapsed EOC, FTC or PPC.
Patients with a known history of hepatitis C (HCV) will be eligible if they have an undetectable viral load; if the patient received treatment for HCV, then that treatment must have been completed at least three weeks prior to enrollment
Prior treatment with talimogene laherparepvec or any other oncolytic virus.
Sexually active subjects and their partners unwilling to use a male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec.
Prior treatment with any therapy targeting mutant IDH1 (including BAY1436032)
Prior treatment with TGR-1202
Prior treatment with lenvatinib.
Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or subjects who refuse standard treatment
Prior treatment with TRC105
Current treatment on another therapeutic clinical trial
Previous treatment with poziotinib prior to study participation.
Agreeable and clinically feasible pre-treatment biopsy
No prior treatment by cetuximab except if given for primary treatment (locally advanced disease) with no progressive disease for at least 4 months following the end of prior cetuximab treatment.
Arrhythmia requiring treatment which is not stabilized by the treatment