2030 lines (2029 with data), 505.1 kB

Patients with newly diagnosed, unresectable, metastatic and measurable ASPS will also be eligible if they show clinical evidence of disease progression (including history and increasing physical symptoms); on-study documentation will include a physician’s rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain)
Patients with evidence of distant metastases or leptomeningeal disease (LMD) are excluded
Patients must have evidence of disease progression per RECIST 1.1 prior to enrollment or have evidence of cancer-related pain requiring symptom management with narcotic analgesics
Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed.
Patient’s current disease state must be one for which there is no known curative therapy
The subject has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine
The patient must have experienced disease progression or intolerance as outlined above after treatment with 1 or more prior chemotherapies
Elevation in tumor markers without radiographic evidence of disease progression is not satisfactory for progression on previous treatment
Histologically-confirmed angiosarcoma that is not amenable to curative intent surgery (e.g., metastatic or bulky disease and disease for which surgical resection would carry an unacceptable risk to the patient). Pathology report will be reviewed by sponsor prior to randomization.
Must have no congenital heart disease
Intrinsic lung disease resulting in dyspnea
Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
Patients must have had =< 1 prior cytotoxic regimen for metastatic disease (unless enrolling in the Progressive Brain Metastases Cohort); note that endocrine and immunotherapies do not count as cytotoxic regimens
Patients must not have unequivocal disease progression (by RECIST v1.1) during the first cycle; patients must have disease assessed using the same method as baseline within +/- 5 days of the day 56 scheduled assessment (between days 51-55 of cycle 1, or days 1-5 of cycle 2); all disease must be assessed and documented on the follow-up tumor assessment form (RECIST 1.1)
Patient MUST have had progressive disease (radiographic or clinical) while on arm 1 single agent nivolumab while registered to A091401
Patients removed from any immunotherapy for reasons other than progressive disease, including arm 1 single agent nivolumab of A091401, are NOT eligible for re-registration
Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
Patients must have histologically or cytologically confirmed extensive stage small cell lung cancer and must be a candidate for systemic therapy; NOTE: The extensive disease SCLC classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive disease patients are defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy
Patient must not have leptomeningeal disease
Patients must also have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; disease X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; if there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan should be performed at baseline (within 42 days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment form
Patients with recurrent disease or multiple primaries are ineligible
Primary surgical debulking before protocol therapy is permissible; this would include removal of gross symptomatic disease in the pelvis and/or vagina\r\n* Exenterative surgery is not permissible; patients with complete resection of gross recurrent disease are eligible
Patients with evidence of disease outside of the pelvis, including presence of positive periaortic or inguino-femoral nodes
Progression on lenalidomide as part of first line therapy (lenalidomide-refractory disease)\r\n* Lenalidomide-refractory disease is defined as disease progression on or progression within 60 days of the last dose of a lenalidomide-based treatment; patients should have received at least 2 cycles of a lenalidomide-based regimen to be evaluable for refractoriness; examples: 1) progression on lenalidomide maintenance therapy after initial induction +/- consolidation; 2) initial response followed by progression on continuous lenalidomide-dexamethasone +/- elotuzumab or daratumumab
Pomalidomide naive disease
Patients cannot have:\r\n* Central nerve system involvement\r\n* Primary refractory multiple myeloma, where primary refractory multiple myeloma is defined as disease that is nonresponsive – patients who have never achieved a minimal response (MR) or better – with any therapy over the course of their disease; it includes patients who never achieve MR or better in whom there is no significant change in M-protein and no evidence of clinical progression as well as patients who meet criteria for true progressive disease (PD)\r\n* Primary or secondary plasma cell leukemia\r\n* Light-chain (AL) amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome\r\n* Known active hepatitis C based on:\r\n** +hepatitis C virus (HCV) antibody (confirmed)\r\n** +HCV RNA\r\n** Liver disease with history of positive serology\r\n** Note: patients with a prior history of hepatitis C that has been successfully eradicated with antiviral therapy are eligible\r\n* Known hepatitis B surface antigen positivity\r\n* Previous hypersensitivity to any of the components of the study treatment\r\n* Prior history of erythema multiforme with thalidomide or lenalidomide treatment
Prior use of ibrutinib is allowed unless patient has had disease progression while receiving ibrutinib
Patient must have chemosensitive disease as defined by at least a partial response to salvage therapy at their latest assessment
For de novo stage IV NSCLC patients (patients with metastatic disease at first presentation), primary disease must be treatable with local therapy in the form of SBRT or hypofractionated radiation. If the primary disease is found in the peripheral or central lung parenchyma without nodal disease, for instance, SBRT may be employed at the discretion of the treating institution. If primary disease is more advanced with involvement of the mediastinum (T4 tumor, N1-N3 disease, etc.), these volumes should be technically treatable with hypofractionated radiation; surgery should only be used for metastatic tumors that can be completely resected by lobectomy, segmentectomy, or wide wedge resection.
If primary disease in the thoracic cavity was previously treated with local therapy in the form of surgery, any local/regional disease recurrence should be technically treatable with SBRT or hypofractionated radiation after induction systemic therapy.
Disease must be cluster of differentiation (CD)30 positive
Patients’ disease must not have micropapillary components
Leptomeningeal disease
No late relapse with completely surgically resectable disease; patients with late relapses (defined as relapse >= 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable are not eligible; patients with late relapses who have unresectable disease are eligible
No secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression
Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression)
Patients must have disease that is not amenable to potentially curative resection or ablative techniques or that has recurred following ablative techniques. In addition, disease must not be amenable to transhepatic arterial chemoembolization (TACE) or must have progressed on TACE. Patients must not be candidates for liver transplantation.
Clinical nodal staging of N2 or N3 disease
Pathologic nodal staging of N2b, N2c, or N3 disease
The study is open to all males and females who meet the following inclusion criteria at\n        screening and baseline to participate in the study.\n\n        To be included to participate in this study each patient must:\n\n          -  be ? 18 years of age;\n\n          -  have an Eastern Cooperative Oncology Group performance status of 0-1 (not declining\n             within past 2 weeks, see Appendix 1);\n\n          -  have confirmed HER2 gene amplified tumor fluorescence in-situ hybridization (FISH,\n             HER2/cep17 ratio > 2) or HER2 overexpression (IHC 3+) or documented HER2 gene\n             mutation. Documentation of HER2 status using FDA approved test(s) for HER2 testing\n             specific for HER2 breast and gastric cancer is required prior to screening;\n\n          -  for part 1:\n\n               1. Patients with HER2 positive (defined as documented overexpression or\n                  amplification or mutation) metastatic breast cancer who have experienced disease\n                  progression following at least 2 prior anti-HER2 therapies for metastatic disease\n                  that contain trastuzumab with or without pertuzumab, prior T-DM1, or lapatinib\n                  therapy is required;\n\n               2. Patients with HER2 positive metastatic gastric cancer who have disease\n                  progression on prior trastuzumab therapy;\n\n               3. other HER2-positive solid tumors (defined as documented overexpression or\n                  amplification or mutation) that have no approved targeted agent as standard of\n                  care\n\n          -  for part 2:\n\n               1. Patients with HER2 positive metastatic breast cancer who have experienced disease\n                  progression after at least 2 prior anti-HER2 therapies for metastatic disease\n                  that contain trastuzumab with or without pertuzumab, prior T-DM1, or lapatinib\n                  therapy is required;\n\n               2. Patients with documented HER2 mutated NSCLC whose disease progressed on prior\n                  therapy;\n\n               3. Patients in Part 2 extension must have at least one measurable lesion as defined\n                  by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;\n\n          -  Left ventricular ejection fraction within institutional limits of normal (by multi\n             gated acquisition scan or echocardiography;\n\n          -  have the required screening laboratory values including the following parameters:\n\n               1. Absolute neutrophil count ? 1.5×109/L (1,500/mm3);\n\n               2. Platelets ? 75×109/L (75,000/mm3);\n\n               3. Hemoglobin ? 9.0 g/dL (90 g/L);\n\n               4. Total bilirubin ? 1.5× upper limit of normal (ULN);\n\n               5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? 2.5×ULN;\n                  for patients with liver metastases, ALT and AST ? 5×ULN;\n\n               6. Serum creatinine ? 1.5×ULN;\n\n          -  have a life expectancy of > 12 weeks;\n\n          -  for female patients who are of child bearing potential, a negative serum pregnancy\n             test result before study entry. A female patient of childbearing potential is one who\n             is biologically capable of becoming pregnant. This includes women who are using\n             contraceptives or other means of birth control or whose sexual partners are either\n             sterile or using contraceptives;\n\n          -  and who have provided informed consent by signing the informed consent form.\n\n        Main Exclusion Criteria:\n\n        Patients who meet any of the criteria listed below will not be eligible for participation\n        in this study. A patient will not be eligible for study participation if:\n\n          -  is unable or unwilling to swallow pyrotinib;\n\n          -  has been < 2 weeks since the last radiotherapy, chemotherapy, hormone therapy, surgery\n             or molecule-target therapy (< 6 weeks if chemotherapy included nitrosoureas or\n             mitomycin);\n\n          -  the bone or skin is the only site of disease (for Part 2 extension only);\n\n          -  has pleural or peritoneal only disease;\n\n          -  has uncontrolled ? grade 2 hypokalemia and hypomagnesemia;\n\n          -  has had other cancer(s) within 5 years prior to screening with the exception of\n             contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or\n             adequately treated basal or squamous cell carcinoma of the skin;\n\n          -  has active central nervous system (CNS) metastases, as indicated by clinical symptoms,\n             cerebral edema, and/or progressive growth (patients with a history of CNS metastases\n             or cord compression are allowable if they have been definitively treated and have been\n             clinically stable for at least 4 weeks, and off steroids and anticonvulsants, before\n             first dose of study drug);\n\n          -  has either QTcF prolongation (> 470 ms for female and > 450 ms for male), a known\n             history of QTcF prolongation or Torsade de Pointes; or is on drugs that are required\n             for existing medical conditions and that may result in QT prolongation (e.g.,\n             anti-arrhythmic drugs); patients who use medications that have a minimal impact on the\n             QTcF interval in the Arizona-CERT criteria are allowed to participate in this study at\n             Investigator's discretion based on his/her clinical assessment);\n\n          -  has a significant chronic or recent acute gastrointestinal disorder with diarrhea as a\n             major symptom (e.g., Crohn's disease, malabsorption, or ? grade 2 diarrhea of any\n             etiology at baseline);\n\n          -  has participated in any other investigational drug clinical studies within the last 4\n             weeks;\n\n          -  is concurrently receiving other anti-tumor therapies at time of study screening visit;\n\n          -  has an active infection (per Investigator judgment);\n\n          -  has a history of immunodeficiency including seropositive for human immunodeficiency\n             virus, or has other acquired or congenital immunodeficient disease;\n\n          -  has evidence of uncontrolled heart disease, including (1) congestive heart failure\n             (New York Heart Association functional classification) of ? 2), (2) angina requiring\n             treatment (3) myocardial infarction within the past 12 months, or (4) any clinically\n             significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment\n             or intervention;\n\n          -  has allergies or a known history of hypersensitivity to any components of the\n             pyrotinib;\n\n          -  is female and of childbearing potential (WOCBP) who is unwilling or unable to use an\n             acceptable method (barrier methods only) to avoid pregnancy for the entire study\n             period and for up to 28 days post last dose;\n\n          -  is female and pregnant (or found to be pregnant at screening) or breastfeeding;\n\n          -  evidence of significant medical illness or an abnormal laboratory finding, which\n             according to the Investigator's judgment, will substantially increase the risk of\n             participation in and completion of the study. Including, but not limited to, serious\n             ongoing infection (ie, requiring intravenous antibiotic or antiviral agent),\n             uncontrolled major seizure disorder, or significant pulmonary disorder (e.g.\n             interstitial pneumonitis, pulmonary hypertension); hypertension (> grade 3), severe\n             diabetes (uncontrolled > grade 3 hyperglycemia), serious ongoing infection or thyroid\n             disease;\n\n          -  has a known history of neurological psychiatric disease including epilepsy or dementia\n             that would interfere with patient's ability to participate in the study or to provide\n             consent;\n\n          -  has had prior exposure to any other investigational HER2 targeted agents within 4\n             weeks of screening visit.\n\n          -  is currently taking strong CYP3A4 inhibitor or concomitant meds.
Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
Leptomeningeal disease
Patients must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease,).
Patient must have unresectable disease
Progressive disease during or after treatment with at least one of the agents listed above
Other serious, ongoing, non-malignant disease or infection that would compromise protocol objectives
Subjects must have proven pediatric cancer with confirmation at diagnosis or at the time of recurrence/progression and clinical determination of disease for which there is no known effective curative therapy or disease that is refractory to established proven therapies fitting into one of the following categories:
Current disease state must be one for which there is currently no known effective therapy
Patients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapy
Early or confirmed evidence of progressive disease.
Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, magnetic resonance (MR) spectroscopy, or surgical/pathological documentation of disease
Patients with any disease that will obscure toxicity or dangerously alter drug metabolism
Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.
Multifocal disease or leptomeningeal disease (LM) disease on post-operative MRI;
(For progression based solely on worsening of non-target or new, non-measurable disease) confirmation by an additional scan at least 4 weeks after the initial scan unless it is accompanied by correlative symptoms. In addition, all the following must hold:
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
Disease Characteristics and allowable prior therapy:
Active coronary artery disease
Active infectious disease considered by the Investigator to be incompatible with the protocol.
Has metastatic disease defined as disseminated disease distant to the initial/primary site of diagnosis, and/or must have locally recurrent disease that has been previously treated (with either surgery, radiotherapy, or systemic therapy), and is not amenable to either curative surgery, radiotherapy, or concurrent chemoradiotherapy treatment.
Rapidly progressive disease.
History within 3 months prior to treatment of grade 3-4 gastrointestinal (GI) bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolus, or other uncontrolled thromboembolic event
Refractory/relapsed disease following DNMTi failure; refractory disease defined as either 1) failure to achieve an objective response after at least 4 cycles of DNMTi therapy, or 2) failure to achieve an objective response with clear progressive disease on bone marrow biopsy after at least 2 cycles of DNMTi therapy; relapsed disease is defined as having progressive disease after achieving an objective response after at least 2 cycles of DNMTi therapy; previous DNMTi therapy may include 5’azacitidine, decitabine, or DNMTi therapy currently in clinical trials (e.g. SGI-110 [guadecitabine], ASTX727 or CC-486); to be considered DNMTi treatment failure, during each prior treatment cycle, patients must have received minimum dosing of:\r\n* Decitabine 15 mg/m^2 daily x 5 days, or\r\n* 5’azacitidine 50 mg/m^2 IV/SC daily x 5 days,\r\n* SGI-110 (guadecitabine) 60 mg/m^2 SC daily x 5 days, or\r\n* Oral DNMTi therapy with ASTX727 20/100 mg daily x 5 days, or\r\n* Oral DNMTi therapy with CC-486 200 mg daily x 14 days
Primary refractory disease (i.e. never responded (? MR) to any prior therapy)
Leptomeningeal disease
Patients must have at least ONE of the following: 1) Recurrent/progressive disease at any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease
Patients with disease of any major organ system that would compromise their ability to withstand therapy.
Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
Currently taking disease modifying rheumatoid drugs (DMRDs)
Have high-risk relapsed or refractory Hodgkin lymphoma (HL), defined as at least one of the following:\r\n* Primary refractory disease to front-line therapy\r\n* Relapse within 1 year of completing front-line therapy\r\n* Extranodal involvement at the time of pre-ASCT relapse\r\n* B symptoms at pre-ASCT relapse\r\n* More than one type of pre-ASCT salvage therapy required
At least 2 weeks since last radiotherapy. If radiation was localized to the only site of measurable disease, there must be documentation of disease progression of the irradiated site. Subjects must have recovered from all acute toxicities from radiotherapy.
Disease progression within 6 months after the last treatment.
Measureable disease (defined as at least 1.5 cm in diameter).
In the dose de-escalation cohort: subjects must have evaluable disease
Subjects with leptomeningial disease or neoplasms in the last 5 years
BCG-unresponsive disease as defined as: (a) Persistent or recurrent CIS (+/- recurrent Ta/T1 disease) within 12 months of receiving adequate BCG (at least five of six doses doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (b) Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG (at least five of six doses of an initial induction course plus either at least two of three doses of maintenance therapy or at least two of six doses of a second induction course); or (c) T1 high-grade disease at the first evaluation following an induction BCG course alone (at least five of six doses of an initial induction course).
The patient must have multiple sites of metastatic disease with at least one lesion amenable to treatment with stereotactic radiation therapy (SBRT) in the lung or liver and at least one lesion not being irradiated and meeting RECIST 1.1.
Ongoing or active gastritis or peptic ulcer disease.
EXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Life-threatening visceral disease or other severe concurrent disease
EXCLUSION CRITERIA FOR THIRD-LINE THERAPY: Life-threatening visceral disease or other severe concurrent disease
Malignant disease, other than that being treated in this study.
Patients who have been infected with HBV or HCV including those with inactive disease.
Patients with progressive extracranial disease will not be excluded
Patients may have progressive systemic disease
Oligometastatic state is defined by =< 3 active sites of disease, including the primary site
Prior ACT therapy should be completed, and residual disease documented by either radiographic progression or active disease observed on biopsy (i.e. hematologic or solid tumor malignancy must be deemed active by the treating investigator); the investigator may deem that the disease is active on the basis of a pre-treatment biopsy demonstrating viable tumor cells or clinical progression of disease (i.e. RECIST progression is not required)
Disease suitable for assessment by pre- and post-biopsies
Radiographic evidence of measurable disease tumor lesion (? 1cm in greatest dimension) or nodal disease (>1.5cm in greatest dimension)
Malignant disease, other than that being treated in this study.
Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1
Leptomeningeal disease
Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of therapy, or a 50% increase of baseline disease measurements after achieving a clinical response
Patients with leptomeningeal disease are not eligible for participation\r\n* Please note: leptomeningeal enhancement is not an exclusion
Pre-abiraterone and pre-enzalutamide with demonstrated evidence of progressive disease. Defined as at least one of the following:
Subjects may not have presence of active CNS disease or extramedullary disease.
Documented disease progression within 6 months prior to study registration, as defined by RECIST criteria
Disease status:
Leptomeningeal disease
Extent of disease\r\n* Unresectable
Subject’s current disease state must be one for which there is no known curative therapy
Has experienced documented objective radiographic or clinical disease progression during or after receiving more than 1 line of therapy.
Lesions that have had definitive external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation or brachytherapy must show evidence of progressive disease to be deemed a target lesion
Known brain/leptomengial involvement of the disease, active neurological disease, dementia
Disease progression at study entry
Known leptomeningeal disease
Patients who have an option for any treatment with proven clinical benefit for their lymphoid malignancy at current state of disease.
Confirmed evidence of relapse/disease progression from immediately prior MM therapy or relapsed and refractory to the immediately prior treatment; relapsed and refractory disease is defined as those who are non-responsive (< minimal response) on salvage therapy or experience disease progression within 60 days of last therapy in patients who have achieved an MR or better to previous therapy; relapsed disease is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy but does not meet IMWG criteria for relapsed and refractory
Objective, documented evidence of disease progression on study entry
Participants who achieve either a partial response or stable disease >= 4 months must agree to undergo a tumor biopsy, if safe and feasible, at the time of progressive disease while on study drug everolimus
Unifocal primary disease NOTE: Patients with multifocal and/or multicentric in breast cancer, or evidence of EIC are NOT eligible. Patients with contralateral disease will remain eligible.
Progressive disease on bendamustine within 6 months of cycle 1, day 1
Concurrent hepatic veno-occlusive disease (VOD) based on clinical examination
Inlcusion criteria:\n\n        - Adult patients with histologically or cytologically confirmed cholangiocarcinoma at the\n        time of diagnosis.\n\n        Patients with cancers of the gallbladder or ampulla of Vater are not eligible.\n\n        - Patients must have received at least one prior regimen containing gemcitabine with or\n        without cisplatin for advanced/ metastatic disease. Patient should have evidence of\n        progressive disease following prior regimen, or if prior treatment discontinued due to\n        toxicity must have continued evidence of measurable or evaluable disease.\n\n        Exclusion criteria:\n\n          -  Prior or current treatment with a MEK or selective FGFR inhibitor\n\n          -  insufficient organ function\n\n               -  ANC < 1,000/mm3 [1.0 x 109/L]\n\n               -  Platelets < 75,000/mm3 [75 x 109/L]\n\n               -  Hemoglobin < 109.0 g/dL\n\n               -  Total bilirubin > 1.5x ULN\n\n               -  AST/SGOT and ALT/SGPT > 2.5x ULN (AST and ALT > 5x ULN in the presence of liver\n                  metastases)\n\n               -  Serum creatinine > 1.5x ULN and a calculated or measured creatinine clearance <\n                  45 mL/min\n\n               -  Inorganic phosphorus outside of normal limits\n\n               -  Total and ionized serum calcium outside of normal limits\n\n        Other protocol-defined inclusion/exclusion criteria may apply.
Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
Patients must have bi-dimensionally measurable disease (at least 1 cm); NOTE: patients with fully resected disease are eligible, and will be evaluable for all toxicity and efficacy endpoints except objective response
Participants must have disease that is not amenable to curative resection
Participants must have evidence of disease progression within 12 months prior to study entry
Patient after progression with to imatinib at the dose of 400 mg as first line treatment. Resistance Progression is defined as a RECIST 1.1 and/or CHOI disease progression while receiving imatinib treatment
Can have recurrent disease from the primary disease (this is definition of oligorecurrent disease) but cannot have any other primary cancer diagnosed or treated within the last 3 years other than cutaneous skin cancer
Ineligible disease sites include the following\r\n* Lymphoma\r\n* Leukemia\r\n* Multiple myeloma\r\n* Primary central nervous system (CNS)\r\n* Peritoneal carcinomatosis \r\n* Colon cancer with liver-only metastatic disease that is treatable with surgical resection
Active rectal diverticulitis, Crohn's disease affecting the rectum, or ulcerative colitis.
Evaluable disease
Diagnosis of:\r\n* B-CLL monoclonal for Kappa light chain with one or more of the following criteria:\r\n** Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia\r\n** Massive (i.e., at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly\r\n** Massive nodes (i.e., at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy\r\n** Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months\r\n** Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs:\r\n*** Unintentional weight loss of 10% or more within the previous 6 months;\r\n*** Significant fatigue (i.e., Eastern Cooperative Oncology Criteria [ECOG] performance status [PS] 2 or worse; inability to work or perform usual activities);\r\n*** Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of infection; or\r\n*** Night sweats for more than 1 month without evidence of infection\r\n*** Patients who have resistant disease after primary treatment\r\n*** Patients who have a short time to progression after the first treatment (< 2 years) OR\r\n* Indolent or aggressive B-cell lymphoma (or other B-cell neoplasm) monoclonal for Kappa-light chain with measurable disease after receiving at least one chemotherapy regimen that includes rituximab or an equivalent monoclonal antibody OR\r\n* Multiple myeloma monoclonal for Kappa-light chain with measurable disease after receiving at least one chemotherapy regimen
Progressive disease on single-agent trastuzumab emtansine or a trastuzumab emtansine-containing regimen during the parent study or before starting the extension study, with the exception of participants from study TDM4688g (NCT00943670) with early disease progression who went on to receive pertuzumab + trastuzumab emtansine treatment and have not experienced further disease progression on the combination regimen
Patients with unresectable disease are eligible
Patients who undergo surgical resection will be allowed regardless of human papilloma virus (HPV) status provided they have one of the following criteria: \r\n* Positive margins on pathology\r\n* Evidence of extracapsular spread on nodal pathology\r\n* Gross residual disease on postoperative or simulation imaging\r\n* N2/3 disease\r\n* T3/4 disease\r\n* Multifocal perineural invasion and/or lymphovascular space invasion
All patients must have experienced disease progression on or after their most recent systemic therapy.
Ocular surface disease at the time of enrollment
Have disease that can be clinically evaluated for improvement or progression. In the dose-expansion phase of the study, subjects must have disease that is measurable, as defined by the RECIST Version 1.1 criteria for solid tumors (Eisenhauer et al, 2009) or the Lugano criteria for lymphoma (Cheson et al, 2014).
Patients with clinical progression but without radiographically recurrent or radiographically progressive disease
For Daratumumab + lenalidomide + dexamethasone (D-Rd) regimen: relapsed or refractory disease
Has disease that is suitable for local therapy administered with curative intent
Serious nonmalignant disease
Participants with widespread, definitive leptomeningeal disease
Evidence of other immune related disease /conditions.
Has measureable disease by RECIST 1.1 criteria as assessed by the local site investigator/radiology.
Has documented disease-free interval (DFI) > 8 weeks after completion of initial therapy; DFI is from the time of completion of initial treatment (from date last known disease-free at end of initial treatment) to the diagnosis of local or loco-regional recurrence
Relapsed or refractory disease after at least 1 prior regimen, defined using the 2014 Lugano classification
Progressive, radioactive iodine-refractory, loco-regional recurrent or metastatic disease.
Are progressive.
The patient has serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
Cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not confined to:
Microsatellite stable disease determined by IHC and/or polymerase chain reaction (PCR).
Disease measurability:
Absolute neutrophil count (ANC) >= 750/uL if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); a subject will not be excluded because of pancytopenia >= grade 3 if it is due to disease, based on the results of bone marrow studies
Platelet count >= 50,000/uL if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); a subject will not be excluded because of pancytopenia >= grade 3 if it is due to disease, based on the results of bone marrow studies
Hyperleukocytosis (>= 50,000 blasts/uL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
Patients must have previously untreated disease (except for one week or less of corticosteroids)
Has MM defined by the IMWG criteria with evidence of disease progression and:
At least one previous treatment for WM with either documented disease progression or no response (stable disease) to the most recent treatment regimen
Disease status requirement:
Disease not amenable to curative or transplant surgery ([Barcelona Clinic Liver Cancer [BCLC] Stage B); disease must be reviewed by members of disease management team at the local enrolling institution and be amenable to deb-TACE to treat all sites of disease in one session; for the dose escalation, regional lymphadenopathy and sub-centimeter pulmonary nodules are allowed as well as segmental portal vein involvement
Experienced documented objective radiographic or clinical disease progression during first-line therapy or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) or taxane (docetaxel) for unresectable or metastatic disease
progressive disease while receiving androgen deprivation therapy
Disease status
Subjects must be considered poor prognosis by the following parameters: 1) right or left portal vein involvement (NOTE: subjects with main portal vein involvement are excluded), 2) multi-focal disease (more than 3 tumors regardless of size) AND/OR 3) diffuse disease considered amenable to liver directed therapy
All disease must be amenable to embolization in one or two procedures
Patients with a condition related to their cancer or leptomeningeal disease requiring urgent intervention that has not been clinically managed or stabilized prior to the time of consent
Nodal disease as detected by clinical exam or CT
Patients who are on active surveillance for untreated localized disease may not participate in this study
Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 12 months prior to study enrollment; this assessment is performed by the treating investigator; evidence of progression by RECIST criteria is not required
Subjects with bulky visceral disease defined as > 4 cm
Participants with widespread, definitive leptomeningeal disease
Documented radiological evidence for disease progression (measurable or nonmeasurable) =< 12 months prior to enrollment
Radiographic evidence of leptomeningeal dissemination, gliomatosis cerebri, infratentorial tumor, or disease at sites remote from the supratentorial brain.
Radiologic evidence of disease progression within 6 months prior to randomization. If the patient received other intervening therapy after documented disease progression, further disease progression must be documented after the completion of the intervening therapy
Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
Patient must have disease that has either relapsed or is refractory to prior therap
Patients with neuroblastoma who do not have measurable disease but have iodine-131 - meta-iodobenzylguanidine positive (MIBG+) evaluable disease are eligible.
Diagnosed with residual pathologic disease after being surgically rendered free of disease with negative margins following complete resection
Part F only: Patients with documented HTLV-1 infection and histologically or cytologically proven ATLL of any stage, and who are intolerant to, or have disease that is relapsed/refractory after, at least one prior therapy
Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
Must have had disease progression while on abiraterone acetate alone or abiraterone acetate in combination with other investigational agents based on: \r\n* PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart and/or\r\n* Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or PCWG2 for patients with bone disease
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): Presence of disease progression on the most recent disease evaluation
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): Presence of disease progression on the most recent disease evaluation
Progressive disease before initiating study treatment
Malignant disease, other than that being treated in this study
Subject meets disease-specific requirements per protocol
Patients must evidence of disease progression, either clinically or radiographically, within the 12 weeks prior to study enrollment, as determined by the investigator enrolling the patient on the study
Subject must be non-refractory to bortezomib (Refractory is defined: progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy).
TREATMENT EXCLUSION: Subjects with rapidly progressive disease, defined as kinetic failure to previous chemotherapy
TREATMENT EXCLUSION: Bulky disease (defined as a 10 cm mass or mediastinal disease with a transverse diameter exceeding 33% of the transthoracic diameter)
Biopsy proven confirmation of relapsed disease.
Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
Known underlying collagen vascular disease or intrinsic lung disease that could complicate expected sequelae of radiation (idiopathic pulmonary fibrosis, Wegener’s granulomatosis)
Relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
Known cerebral/meningeal disease
Must have evidence of progressive disease with biochemical (i.e. rising CA-125) and/or radiologic progression
biopsy-proven refractory disease after frontline chemo-immunotherapy
For subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
Patient has pathologically confirmed SCCHN (oral cavity, oropharynx, larynx, hypopharynx) with evidence of local and/or locoregional recurrence; laryngeal tumors will only be included if there is evidence of extralaryngeal spread, or there is associated nodal disease; for all other sites, superficial tumors can only be included if there is associated nodal disease
Previous treatment with nelarabine for relapsed or refractory disease
Bulky disease
Radiographic evidence of persistent, progressive, or recurrent disease in an area previously treated with TACE and determined from 3 months or more (no upper time limit) after initial TACE; this evaluation should be within 6 weeks of date of study eligibility
Patients must have disease that is suitable for repeated measurement, either
Patients with malignant disease other than that being treated in the study.
Participants must be in first recurrence or have disease that is primarily refractory to conventional therapy
A diagnosis of post-transplant lymphoproliferative disease (PTLD)
Patient may not have disease limited to a single skin or bone site, with the following exceptions:\r\n* Central nervous system (CNS) risk lesions/special site disease: patients with single bone sites that are CNS-risk (sphenoid, mastoid, orbital, zygomatic, ethmoid, maxillary, or temporal bones, the cranial fossa, pituitary gland or neurodegenerative disease) or are “special sites” (odontoid peg, vertebral lesion with intraspinal soft tissue extension) require systemic therapy as standard of care and thus ARE eligible for the study\r\n* Functionally critical lesions: a single lesion not described above which may cause “functionally critical anatomic abnormality” wherein attempts at local therapy (such as surgical curettage or radiation) would cause unacceptable morbidity; these patients may be enrolled with approval of the principal investigator (PI) and documentation of the rationale justifying systemic therapy
requiring treatment for relapsed or relapsed/refractory disease
Human Papillomavirus (HPV)+ disease of the oropharynx
Patients must not have experienced confirmed progressive disease since the time of their transplant
Patients with any history of relapsed/refractory disease, or who have progressed at any time since beginning induction therapy are not eligible; patients who have evidence of residual disease by FISH, cytogenetics, SNP array, or flow cytometry without any measurable nodal disease or morphologic evidence of disease in the bone marrow or peripheral blood are eligible
Have histologically confirmed diagnosis of RRP that involves the trachea, lungs, and/or larynx; if a subject is enrolled with laryngeal disease only, the subject must have undergone at least 3 or more surgeries/procedures in any one year to remove the lesions from their larynx; subjects must have evaluable disease either based on RECIST 1.1 and/or endoscopic parameters, as discussed above
Any episode of progressive disease during aggressive multi-drug frontline therapy.
Current disease state must be one for which there is currently no known curative therapy
Documented disease progression per RECIST v.1.1 during or immediately after last therapy according to any of the aforementioned criteria.
Disease status: patients with malignancy are to be referred in remission for evaluation, except in cases of virus-associated malignancy who may be referred at any time; should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to his/her primary hematologist-oncologist for treatment; if this course of action is not in the best interest of the patient according to the clinical judgment of the PI, then the patient may receive standard treatment for the malignant disease under the current study, although this should only occur as a bridge to transplant; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off the study; patients receiving standard therapy will be told about the therapy, associated risks, potential benefits, alternatives to the proposed therapy, and the availability of receiving the same treatment elsewhere, outside of a research protocol
Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites
ARM 2 - A: Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites
Prior radiation therapy is allowed as long as the irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least 3 weeks prior to enrollment; if the irradiated area is the only site of disease, there will be progressive disease
Patients must have at least one of the following for a diagnosis/disease status:\r\n* Unresectable disease\r\n* Metastatic disease\r\n* Medically unfit for surgical resection but with an expected survival of > 3 months, Eastern Cooperative Oncology Group (ECOG) < 2 and New York Heart Association (NYHA) status =< II\r\n* Disease where no conventional therapy leads to a survival benefit > 6 months in the respective cohort and line of therapy for which the patient is otherwise eligible\r\n* Actionable alterations determined by FoundationOne
Radiologically confirmed disease progression
Hyperparathyroidism, Paget's disease or osteomalacia
Unstable cardiac disease, including unstable angina or unstable hypertension, or need to change medication within 6 weeks of provision of consent due to lack of disease control
Recurrent disease that presents >100 days after, or minimal residual disease (MRD) that presents > 30 days after either:
Prior radiation therapy is allowed as long as the irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least three weeks prior to enrollment; if the irradiated area is the only site of disease, there must be evidence of progressive disease
Disease-related platelet transfusion within 8 weeks of registration
PHASE IB: Patients in the expansion cohort must have a measurable site of disease according to RECIST (v 1.1) that has not been previously irradiated, or evidence of at least 20% progression in a previously irradiated lesion, and assessed by imaging within 28 days prior to registration for protocol therapy
Known distant metastatic disease (e.g. pulmonary or hepatic metastases)\r\n* Subjects with malignant lymphadenopathy in the abdomen or pelvis considered appropriate for radical cystectomy and lymphadnectomy with the goal of complete resection of all malignant disease are allowed
Unresectable disease. Patients with resectable disease may be enrolled after having refused surgery after a documented consultation with a surgeon.
Patient with clinically positive nodal disease
Patients with pathologically proven nodal disease
Progressive disease and no effective therapy exists
Measurable disease by physical exam or CT scan, or evaluable disease by CA-125; (NOTE: CA-125-evaluable disease is defined as serum CA-125 >= 2 x ULN that is determined by the treating clinician to be due to recurrent ovarian, fallopian tube, or primary peritoneal cancer)
All subjects must have measurable disease in 2-dimensions on MRI scan of the brain; disease should be consistently measured with the two largest perpendicular dimensions
INCLUSION CRITERIA FOR STRATUM C: All subjects must have measurable disease in 2-dimensions on MRI scan of the brain and/or spine; disease should be consistently measured with the two largest perpendicular dimensions
Leptomeningeal disease
Histologic diagnosis of malignant melanoma, stages IIB-IV is radiologically confirmed complete clinical remission (cCR) without clinical evidence of disease
Progressive, histologically or cytologically diagnosed low or intermediate grade, neuroendocrine tumors confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) or a pathology laboratory at the enrolling institution; disease progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progression of disease or any new lesions seen on 68-Gallium DOTATATE within 18 months prior to enrollment (per principal investigator [PI] discretion and if 68-Gallium DOTATATE is performed at the enrolling institution)
Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis
Hyperleukocytosis (>= 50,000 blasts/uL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
Patients with NHL must have objective, documented evidence of disease prior to study entry
ELIGIBILITY FOR SCREENING: Any patient with diagnosis of either:\r\n* EBV positive Hodgkin’s lymphoma\r\n* EBV positive non-Hodgkin’s lymphoma (regardless of histologic subtype)\r\n* EBV (associated)-T/NK-lymphoproliferative disease\r\n* Severe chronic active EBV (CAEBV)** AND\r\n* In first or subsequent relapse (Group A)\r\n* With active disease persisting despite therapy (Group B)\r\n* With active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of chronic lymphocytic leukemia (CLL) (Group C)\r\n** CAEBV is defined as patients with high EBV viral load in plasma or peripheral blood mononuclear cell (PBMC) (> 4000 genomes per ug PBMC deoxyribonucleic acid [DNA]) and/or biopsy tissue positive for EBV
ELIGIBILITY CRITERIA AT TIME OF TREATMENT: Any patient with diagnosis# of either:\r\n* EBV positive Hodgkin’s lymphoma\r\n* EBV positive non-Hodgkin’s lymphoma (regardless of histologic subtype)\r\n* EBV (associated)-T/NK-lymphoproliferative disease\r\n* Severe chronic active EBV (CAEBV)** AND#\r\n* In first or subsequent relapse (Group A)\r\n* With active disease persist despite therapy (Group B)\r\n* With active disease if immunosuppressive chemotherapy is contraindicated e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter's transformation of CLL (Group C)\r\n** CAEBV is defined as patients with high EBV viral load in plasma or PBMC (> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV\r\n# The disease diagnosis and the group must be noted on the eligibility checklist
Patients in remission who are enrolled on another study where time to progression or disease free survival is a primary endpoint
Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of first line therapy, or a 50% worsening of baseline disease measurements (i.e., lymph node size, splenomegaly, lymphocytosis, anemia, thrombocytopenia, hepatomegaly) after achieving a clinical response
Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
Disease progression (AD worse) in non-risk organs at any time during continuation treatment
Active disease at the end of Stratum I treatment
Disease reactivation in non-risk organs at any time after completion of Stratum I treatment
Patients with progressive disease in risk organs
Eligible patients will be women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma after chemotherapy with no evidence of disease or minimal residual disease for primary or recurrent disease; this may or may not be measurable; these patients would normally enter a period of observation after standard management
Patients must have disease limited to the hemithorax
Patients with any disease that will obscure toxicity or dangerously alter drug metabolism are excluded
Unstable or rapidly progressive disease, including patients who require glucocorticoids for symptomatic control of brain or spinal tumors
Patients with oropharyngeal squamous cell carcinoma may have p16(+) or p16(-) disease; in these patients, p16 status must be known prior to randomization; assessment of p16 status may occur locally or centrally; note: the definition of p16(+) disease is diffuse nuclear and cytoplasmic staining in >= 70% of tumor cells
Patients must have evidence of disease progression prior to enrollment
Patients with rapidly progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy are ineligible.
Advanced stage III, IV (N2C, N3) or surgically unresectable disease or disease that cannot be fully resected, obvious radiologic extracapsular spread (ECS), supraclavicular or matted metastatic disease, > 3 cervical nodes; (these patients will be placed on the quarterback trial due to advanced state of disease and poor prognostic features)
PHASE II: No prior history of allogeneic HCT (one of the following)\r\n* 2nd or greater relapse, with or without extramedullary disease (isolated extramedullary disease is eligible)\r\n* 1st marrow relapse at end of 1st month of re-induction with marrow having >= 0.01% blast disease, with or without extramedullary disease\r\n* Primary refractory as defined as having M2 or M3 marrow after induction\r\n* Subject has indication for HCT but has been deemed ineligible OR
Patients must have histologically or cytologically confirmed papillary RCC\r\n* Patients with bilateral multifocal disease can have tumors localized to the kidney or have metastatic disease\r\n* Patients with sporadic papillary RCC (but without multifocal disease) should have advanced disease that is considered unresectable
Patients must have a diagnosis of transitional cell carcinoma (TCC) of the urinary bladder confirmed at the study institution. The patient must have demonstrated nonmuscle-invasive bladder cancer refractory or recurrent to standard intravesical therapy. Refractory disease is defined as failure to achieve tumor-free status by 6 months of initiation of adequate BCG therapy. Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months of initiation of adequate BCG therapy. Adequate BCG therapy includes at least 6 weeks induction plus 3 additional doses of either induction or maintenance. Patients with a history of other intravesical agents (except nab-rapamycin or gemcitabine) in addition to standard BCG will also be allowed to enroll. All grossly visible disease must be fully resected and pathologic stage will be confirmed at the institution where the patient is enrolled. This will include stage Ta, T1, Tis and exclude all patients with muscle invasion (T2).
Pathologically confirmed GBM (including all histologic variants) at first diagnosis with radiographic evidence of recurrent disease after treatment with radiotherapy and temozolomide;
Patients with leptomeningeal disease
High risk of relapse after HSCT, defined as the presence of minimal residual disease as measured by flow cytometry in the absence of evidence of morphologic disease on a bone marrow biopsy prior to HSCT
Patients with advanced adenocarcinoma of the colon or rectum not curable with surgery or radiotherapy and have been previously treated for their disease with FOLFIRI plus bevacizumab in the first line metastatic setting; patients will only be eligible if their last line of therapy prior to enrolling onto the study was FOLFIRI and bevacizumab received no more than 6 months prior to enrolling in this study; they should have been treated with FOLFIRI plus bevacizumab until disease progression is radiographically documented
Patients must have measurable or evaluable disease; patients with > 10% of the peripheral blood mononuclear cells (PBMCs) having the characteristic abnormal (i.e., cluster of differentiation [CD]3dim, CD4+ CD25+ expressing) fluorescence-activated cell sorting (FACS) profile for circulating ATL cells will be considered to have evaluable disease
At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of >50% over a 2-month period or an unanticipated doubling time of less than 6 months
COHORT B, GROUP 5: MESOTHELIOMA: Patients must have failed a minimum of one previous line of systemic therapy for advanced disease
COHORT B, GROUP 7: GALLBLADDER CANCER OR CHOLANGIOCARCINOMA: Patients must have failed a minimum of one previous line of systemic therapy for advanced disease
Patients taking steroids for disease control or pain management
Patients must have previously received at least one systemic standard care (or effective salvage chemotherapy regimens) for metastatic or unresectable disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
Active rectal diverticulitis, Crohn's disease affecting the rectum or ulcerative colitis (non-active diverticulitis and Crohn's disease not affecting the rectum are allowed).
Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not be a candidate for therapy of proven efficacy for their disease due to an underlying physical condition
Transaminases =< 3.0 x ULN, except in known hepatic disease, wherein may be =< 5 x ULN
Cannot be on systemic agents (chemotherapy) that have central nervous system (CNS) penetration (temozolomide, carmustine [BCNU], lomustine [CCNU], etoposide, Xeloda, carboplatin, Navelbine, bevacizumab, CPT-11 and topotecan; note: please check with study principal investigator [PI] [Dr. Raizer] to clarify other agents not listed) unless they develop or have progressive or persistent leptomeningeal metastases while on these agent(s) and have controlled systemic disease\r\n* NOTE: may continue on intravenous (IV) trastuzumab, pertuzumab, TDM-1, lapatinib or hormonal agents if controlling systemic disease and developed LM while on therapy \r\n* NOTE: patients requiring systemic agents (such as those listed above) are eligible but will not be able to start treatment until after the first assessment by imaging and cytology
Patients with previously untreated or relapsed/refractory disease will be eligible
Complete macroscopic resection of all known disease
Patients with a nonmalignant disease treatable by allogeneic HCT
Patients with an active infectious disease requiring deferral of conditioning; as recommended by an infectious disease specialist
Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens)
Patients must have radiologic evidence of disease progression
Symptomatic nodal disease (i.e., scrotal, penile, or leg edema)
AUTOLOGOUS APHERESIS: CD19+ ALL with any of the following:\r\n* Minimal residual disease (MRD) >= 1% at end of up-front induction therapy\r\n* Hypodiploid (< 44 chromosomes or < 0.95 deoxyribonucleic acid [DNA] index) CD19+ ALL with detectable disease at the end of up-front induction therapy \r\n* Increase in disease burden any time after the completion of up-front induction therapy\r\n* Primary refractory disease despite 2 cycles of an intensive chemotherapy regimen designed to induce remission\r\n* Refractory disease despite salvage therapy\r\n* 1st or greater relapse\r\n* Note: if patient meets CD19+ ALL disease criteria, subsequent receipt of cancer directed therapy that eradicates disease does not preclude them from proceeding with this study
MANUFACTURING SJCAR19: CD19+ ALL with any of the following:\r\n* Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission\r\n* Refractory disease despite salvage therapy\r\n* 2nd or greater relapse\r\n* Any relapse after allogeneic hematopoietic cell transplantation \r\n* 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT
TREATMENT WITH SJCAR19: Detectable disease
Active rectal diverticulitis, Crohn’s disease affecting the rectum or ulcerative colitis (non-active diverticulitis and Crohn’s disease not affecting the rectum are allowed)
Patients must have progressive disease at study entry
Patients must have progressive metastatic castration-resistant prostate cancer (mCRPC). There must be radiographic evidence of disease progression or biochemically (rising PSA levels on successive measurements) recurring disease despite adequate testosterone suppression.
Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator
Extramedullary disease status: patients with isolated CNS disease or isolated testicular disease are not eligible
Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
Have relapsed or treatment refractory disease with ? 10% CD138+ malignant plasma cells immunohistochemistry (IHC) on BM core biopsy, either: \r\n* Following autologous stem-cell transplantation (ASCT)\r\n* Or, if a patient has not yet undergone ASCT, the individual must:\r\n** Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician, and,\r\n** Demonstrate disease that persists after > 4 cycles of induction therapy and that is double refractory (persistence/progression) after therapy with both a proteasome inhibitor and immunomodulatory drug (IMiD) administered either in tandem, or in sequence, or demonstrate intolerance to both classes of agents (IMiD and proteasome inhibitor [PI])
Parkinson’s disease
Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study drugs
Patients with extramedullary disease only are eligible
Primary refractory disease (i.e. never responded with ? MR to any prior therapy)
Measurable  disease of multiple myeloma at the time specified by one of the following:\r\n* If no relapse prior to transplant, values obtained at the time of diagnosis\r\n* If disease relapse prior to transplant and the patient did not have treatment for the relapsed disease prior to transplant, the values obtained at the time of relapse immediately prior to the transplant. \r\n* If disease relapse prior to transplant and the patient did have treatment for the relapsed disease prior to transplant, the values obtained prior to this therapy, ie, the time of relapse
Infratentorial disease (defined as glioblastoma [GBM] derived from cerebellum or brainstem)
Inclusion criteria:\n\n          -  Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression\n             testing\n\n          -  High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+) in archival or\n             fresh tumor biopsy specimen\n\n          -  Documented locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial\n             carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis,\n             ureters, urethra, meeting all of the following criteria:\n\n          -  No prior systemic treatment for locally advanced or metastatic urothelial carcinoma.\n             For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation\n             for urothelial carcinoma, a treatment-free interval > 12 months between the last\n             treatment administration and the date of recurrence is required in order to be\n             considered treatment-naïve in the metastatic setting. Prior local intra-vesical\n             chemotherapy or prior local immunotherapy is allowed.\n\n          -  Ineligibility for cisplatin-based chemotherapy as defined by any one of the following\n             criteria:\n\n               -  Impaired renal function (GFR > 30 but < 60 mL/min/1.73 m2) according to the\n                  modification of diet in renal disease (MDRD) abbreviated formula\n\n               -  Hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies\n\n               -  Grade ? 2 peripheral neuropathy (i.e. sensory alteration or paresthesia including\n                  tingling)\n\n          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.\n\n        Exlusion criteria:\n\n          -  Active symptomatic or untreated brain metastases as determined by CT or MRI evaluation\n             during screening and prior radiographic assessment.\n\n          -  History of autoimmune disease, including but not limited to myasthenia gravis,\n             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,\n             inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid\n             syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré\n             syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.\n\n          -  History or current condition of an uncontrolled cardiovascular disease including any\n             of the following conditions:\n\n               -  Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms\n                  of angina at rest) or\n\n               -  New-onset angina (within last 3 months before the first study drug\n                  administration)\n\n               -  Myocardial infarction (MI) within past 6 months before the first study drug\n                  administration\n\n               -  Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.\n\n          -  Patients with known coronary artery disease, congestive heart failure not meeting the\n             above criteria, or known left ventricular ejection fraction < 50% must be on a stable\n             medical regimen that is optimized in the opinion of the treating physician, in\n             consultation with a cardiologist if appropriate.\n\n          -  Current diagnosis of any retinal disorders including retinal detachment, retinal\n             pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.\n\n          -  Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g.\n             parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis,\n             paraneoplastic hypercalcemia).\n\n          -  Concomitant therapies that are known to increase serum calcium or phosphate levels\n             (i.e. antacids, phosphate-containing laxatives oral/rectal, potassium phosphate) and\n             that cannot be discontinued or switched to a different medication before the first\n             study drug administration\n\n          -  Treatment with systemic corticosteroids or other systemic immunosuppressant\n             medications within 2 weeks before the first study drug administration, or anticipated\n             requirement for systemic immunosuppressive medications during the trial.
Disease status as defined as.
Patient must have relapsed/refractory disease with an indication for treatment
Chylous effusions associated with malignant disease
Deemed to have unresectable disease by surgeon
Active disease meeting at least 1 of the IWCLL 2008 criteria for requiring treatment:\r\n* A minimum of any one of the following constitutional symptoms:\r\n** Unintentional weight loss >10% within the previous 6 months prior to screening\r\n** Extreme fatigue (unable to work or perform usual activities)\r\n** Fevers of greater than 100.5 Fahrenheit for ? 2 weeks without evidence of infection\r\n** Night sweats without evidence of infection\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia\r\n* Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly\r\n* Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy\r\n* Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months\r\n* Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids
Patients must have disease that is not amenable to potentially curative resection
Patient must have a B cell ALL (inclusive of chronic myeloid leukemia [CML] with ALL transformation) or lymphoma and must have relapsed or refractory disease after at least one standard chemotherapy regimen and one salvage regimen; in view of the principal investigator (PI) and the primary oncologist, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment; patients who have undergone autologous SCT will be eligible, and patients that have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they have no evidence of graft versus host disease (GVHD) and have been without immunosuppressive agents for at least 30 days; patients with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor; patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry
Leukocytes ? 750/mcL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); a subject will not be excluded because of pancytopenia ? grade 3 if it is due to disease, based on the results of bone marrow studies
Platelets ? 50,000/mcL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); a subject will not be excluded because of pancytopenia ? grade 3 if it is due to disease, based on the results of bone marrow studies
Hyperleukocytosis (? 50,000 blasts/uL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
Leptomeningeal disease
Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson’s disease.
Any cancer-related therapy for the current disease within 2 weeks of screening (all supportive care measures are allowed)
Patients must have disease that is not amenable to potentially curative resection
Has evidence of leptomeningeal disease
Relapsed or relapsed/refractory disease
Patients must be cetuximab-resistant by fulfilling at least one of the criteria defined below:\r\n* Disease persistence or recurrence within 6 months of completing definitive radiotherapy for locally advanced disease; radiation must have included concurrent cetuximab; induction chemotherapy, if given, may or may not have included cetuximab\r\n* Disease progression during, or within 6 months, of cetuximab treatment in the recurrent/metastatic setting\r\n* Prior cetuximab exposure may have occurred in any line of therapy (first line, second line, etc.) and cetuximab is not required to be the most recent therapy received
Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy
Patients post hysterectomy and free from residual disease
Evidence of disease progression at the time of enrollment
Current medical need for therapy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
Radiologically documented disease progression on previous osimertinib treatment.
Radiologically documented disease progression on or after most recent antitumor therapy.
Evaluable disease by RANO.
Presence of measurable disease per RECIST v1.1; target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment
Asymptomatic or minimally symptomatic disease.
Refractory to approved standard systemic therapy; specifically\r\n* Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan\r\n* Patients with breast and ovarian cancer must be refractory to both 1st line and 2nd line treatments\r\n* Patients with lung cancer must have received at least one platinum-based chemotherapy regimen and at least one Food and Drug Administration (FDA) approved targeted treatment (when appropriate)\r\n* Patients with glioblastoma must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered no evidence of disease [NED]); this includes recurrent glioblastoma (GBM) after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy
Candidate for local consolidation therapy to at least one site of disease
All stages of disease (IA through IVB) where radiation therapy is being considered for local control are eligible. Patients who are concomitantly undergoing systemic therapy for more advanced stage disease are eligible.
Have stable disease or progression on a prior regimen containing infusional 5-FU or capecitabine according to the interpretation of the treating provider
Subject has histologic or cytologic confirmation of metastatic NSCLC. Subjects must have a TPS score available as determined by an FDA approved test. Subject has stable disease or disease progression and is being treated with pembrolizumab therapy as standard of care by the Investigator.
Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization
Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of initial radiation therapy
Patient has leptomeningeal disease
Patients with disease progression prior to enrollment
Patients must have documented IDH1-R132 gene-mutated disease as evaluated by the site
Primary refractory disease
Relapsed or refractory disease after first or later salvage therapy
Isolated extramedullary disease
Evidence of active disease (histological confirmation of reactivation or progression is not required)
Progressive underlying malignant disease or any post-transplant lymphoproliferative disease
Lesions on imaging, by cerebrospinal fluid or with neurological findings that are consistent with leptomeningeal disease or meningeal carcinomatosis.
Has not achieved disease-free status after completion of CCRT administered with curative intent.
Patients must have recurrence or progression of their low-grade glioma after coming off treatment with AZD6244 on PBTC-029 or PBTC-029B, with or without having received additional anti-tumor therapy following discontinuation of AZD6244; the progression must be unequivocal and sufficient to warrant re-treatment in the opinion of the investigator; progression will be defined as either progressive disease (PD) that meets the study definitions of progressive disease by MRI or vision deterioration thought to be related to tumor in patients with optic pathway tumors
Patients must have bi-dimensionally measureable disease defined as at least one lesion that can be accurately measured in at least two planes
Must have biopsy-proven primary refractory disease or relapsed disease after front-line chemo-immunotherapy (with anti-CD20 monoclonal antibody [mAb]) in combination with anthracycline-based chemotherapy) or at least one of the following\r\n* For subjects with DLBCL: relapsed or refractory disease after ? 2 prior line(s) of therapy; for both de novo and transformed disease, patients must have received at least 1 prior regimen with anti-CD20 mAb and anthracycline\r\n* For subjects with FL or SLL: relapsed or refractory disease after ? 2 prior line(s) of therapy\r\n* For subjects with CLL: must be relapsed or refractory disease and\r\n** with no unfavorable cytogenetics and have failed ? 3 prior line(s) of therapy\r\n** with unfavorable cytogenetics including del17p/mutated p53 or unmutated immunoglobulin heavy chain variable region relapsed or refractory disease after ? 2 prior line(s) of therapy which must have included ibrutinib\r\n* For subjects with MCL: relapsed or refractory disease after at least 1 prior regimen with chemoimmunotherapy\r\n* For subjects with Burkitt’s: relapsed or refractory disease after at least 1 prior line of therapy\r\n* Any patient, with subtypes listed above, having either failed autologous HSCT after at least 1 prior regimen, or those patients ineligible for, but not an appropriate candidate, or not consenting to autologous HSCT
Documented disease progression occurring within 12 months from the last treatment with curative intent
(Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study) b. gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: i. any of the following within 28 days before the first dose of study treatment: intra-abdominal tumor/metastases invading GI mucosa, active peptic ulcer disease; patients must be completely recovered, inflammatory bowel disease (including ulcerative colitis and Crohn’s disease), acute pancreatitis, pancreatic duct or common bile duct obstruction, acute diverticulitis, acute cholecystitis, symptomatic cholangitis or recent appendicitis within 1 month of first dose of cabozantinib; patients must be completely recovered from these conditions, clinically significant malabsorption syndrome, c. endocrine disorders, uncontrolled Cushing syndrome despite of adequate medical therapy.
Disease progression by IWG criteria since last therapy
Evidence of leptomeningeal disease on MRI or in cerebrospinal fluid (CSF) for arm 1; ocular or mucosal disease specifically for patients with melanoma in arm 1
Microsatellite stable disease as determined by IHC and/or PCR, or mismatch repair proficient disease as determined by IHC.
Have relapsed or treatment refractory disease with >= 10% CD138+ malignant plasma cells (IHC) on bone marrow (BM) core biopsy, either:\r\n* Following autologous stem cell transplant (ASCT)\r\n* Or, if a patient has not yet undergone ASCT, the individual must:\r\n** Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician, and,\r\n** Demonstrate disease that persists after > 4 cycles of induction therapy and that is double refractory (persistence/progression) after therapy with both a proteasome inhibitor and immunomodulatory drug (IMiD) administered either in tandem, or in sequence.
Progression of disease
Androgen independent prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression concomitant with surgical or medical castration, as demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:\r\n* PSA: two consecutive PSA values, at least 14 days apart, each >= 5.0 ng/mL and >= 50% above the minimum PSA observed during castration therapy or above the pre-treatment value if there was no response\r\n* Measurable disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response\r\n* Non-measurable disease: soft tissue disease: the appearance of 1 or more new lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n* Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression\r\n* Serum PSA >= 5.0 ng/mL\r\n* Castration levels of testosterone (< 50 ng/dL) achieved via medical or surgical castration; surgical castration must have occurred at least 3 months prior to registration; subjects who are not surgically castrate must be receiving medical castration therapy, have initiated such therapy at least 3 months prior to registration, and continue such therapy until the time of confirmed objective disease progression
Paget’s disease of bone
Patients with persistent disease and local recurrence must not be amenable to local treatment.
Three or fewer total sites of active disease (at least one site of active disease to be treated on study must be confined to the abdomen or pelvis excluding liver and must be < 5 cm in greatest dimension as determined by pre-screening cross-sectional imaging)
Patients with active collagen vascular disease (CVD), specifically systemic lupus erythematosus or scleroderma; patients with a history of CVD without evidence of active disease are eligible for enrollment at the discretion of the study PI
Has any evidence of progressive systemic disease (by RECIST 1.1); those with stable systemic lesion may be considered for enrollment
N0 M0 disease
Patient has history of or currently has non-peritoneal surface macroscopic metastatic disease in addition to peritoneal surface malignancy such as macroscopic pulmonary disease or other macroscopic disease outside of the peritoneal cavity
Has had prior systemic anti-cancer therapy for the treatment of bladder cancer. Prior intravesical therapies, whether Bacillus Calmette-Guerin (BCG) (including but not limited to: persistent high-grade disease or recurrence within 6 months of receiving at least two courses of intravesical BCG [at least five of six induction doses and at least two of three maintenance doses]; or T1 high-grade disease at the first evaluation following induction BCG alone [at least five of six induction doses]), chemotherapy or otherwise, will remain eligible.
Known Gilbert’s disease
Immunocompromised status due to:\r\n* Human immunodeficiency virus (HIV) positivity\r\n* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease\r\n** Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed\r\n** Patients with diabetes type I, vitiligo, or alopecia are allowed\r\n* Other immunodeficiency diseases\r\n* Splenectomy
Gleason sum of 7 (with pT3 disease), 8, 9, or 10 based on the radical prostatectomy specimen
Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment.
Inclusion and Exclusion Criteria - Part 1 Inclusion Criteria - Part 1\n\n        • Subject has provided informed consent prior to initiation of any study-specific\n        activities/procedures or subject's legally acceptable representative has provided informed\n        consent prior to any study-specific activities/procedures being initiated when the subject\n        has any kind of condition that, in the opinion of the investigator, may compromise the\n        ability of the subject to give written informed consent.\n\n          -  Age ? 18 at time of informed consent\n\n          -  Biopsy-proven DLBCL excluding DLBCL that represents transformation of indolent NHL\n             Note: Lymphoblastic Lymphoma and Burkitt Lymphoma histology are not eligible\n\n          -  Subject has ? 1 characteristic feature of high-risk DLBCL:\n\n             o High-risk first complete remission (defined as interim PET-CT positive or < complete\n             remission to frontline chemotherapy AND achieved complete remission to\n             platinum-containing salvage)\n\n             o Relapse within 1 year of diagnosis\n\n               -  Secondary aaIPI > 1 (see Appendix D)\n\n               -  Partial response/partial metabolic response after minimum of 2 cycles of\n\n               -  platinum-containing salvage chemotherapy\n\n               -  C-myc rearrangement\n\n          -  aHSCT with high-dose chemotherapy following first (or later) salvage treatment.\n\n          -  PET-CT negative (Deauville score ? 3) 90 days (± 30 days) post aHSCT\n\n          -  Available relapsed and/or diagnostic pathology formalin-fixed paraffin-embedded (FFPE)\n             tumor block or slide samples at the time of enrollment including the successful\n             identification of malignant clone sequences by the central laboratory.\n\n          -  MRD plasma sample collected ? 3 weeks from post aHSCT PET-CT scan\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status ? 2.\n\n          -  Adequate organ function determined ? 3 weeks prior to enrollment defined as follows:\n\n             o Hematological: Absolute neutrophil count (ANC) ? 1.0 x 109/L Platelet count ? 75 x\n             109/L Hemoglobin ? 8 g/dL\n\n             o Renal: Creatinine clearance ? 50 mL/min Cockcroft-Gault equation\n\n             o Hepatic: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x\n             upper limit of normal (ULN) Total bilirubin < 2 x ULN (unless Gilbert's Disease or if\n             liver involvement with lymphoma)\n\n          -  Subject will be available to complete all protocol-required study visits or\n             procedures, and/or to comply with all required study procedures to the best of the\n             subject's and investigator's knowledge including but not limited to:\n\n          -  Completion of up to a 24-month run-in period\n\n          -  Completion of all regularly scheduled study visits including blood draws for\n\n          -  MRD assessment, clinical disease state assessment, PET-CT scans (ie, at time of MRD\n             positivity or relapse), assignment to treatment with blinatumomab\n\n        Other Inclusion Criteria may apply\n\n        Exclusion Criteria - Part 1\n\n        • Clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia,stroke,\n        severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain\n        syndrome, and psychosis\n\n          -  Evidence of CNS involvement with DLBCL\n\n          -  Current autoimmune disease or history of autoimmune disease with potential of CNS\n             involvement\n\n          -  Prior anti-CD19 directed therapies\n\n          -  Prior alloHSCT\n\n          -  Received radiation ? 2 weeks prior to enrollment\n\n          -  Known infection with human immunodeficiency virus or chronic infection with hepatitis\n             B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti-hepatitis C\n             virus positive)\n\n          -  History of malignancy other than DLBCL within the past 3 years with the following\n             exceptions:\n\n             o Malignancy treated with curative intent and with no known active disease present for\n             ? 3 years before enrollment and felt to be at low risk for recurrence by the treating\n             physician\n\n             o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of\n             disease\n\n             o Adequately treated cervical carcinoma in situ without evidence of disease\n\n               -  Adequately treated breast ductal carcinoma in situ without evidence of disease\n\n               -  Prostatic intraepithelial neoplasia without evidence of prostate cancer\n\n               -  Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in\n                  situ\n\n          -  Subject has known hypersensitivity to immunoglobulins or any of the products or\n             components to be administered during dosing.\n\n          -  History or evidence of any other clinically significant disorder, condition or disease\n             (with the exception of those outlined above) that, in the opinion of the investigator\n             or Amgen physician, if consulted, would pose a risk to subject safety or interfere\n             with the study evaluation, procedures or completion.\n\n          -  Women who are pregnant or breastfeeding or planning to become pregnant or breastfeed\n             while receiving blinatumomab and for an additional 48 hours after the last treatment\n             dose of blinatumomab. (Females of child bearing potential should only be included\n             after a negative highly sensitive urine or serum pregnancy test.)\n\n          -  Women of childbearing potential unwilling to use an acceptable method of effective\n             contraception while receiving blinatumomab and for an additional 48 hours after last\n             dose of blinatumomab. Note: The pregnancy, breastfeeding and contraceptive\n             requirements are specific to blinatumomab. The investigator is responsible for\n             providing the subject (male and female) with pregnancy and breastfeeding (female only)\n             avoidance requirements for other medications given during the study.\n\n          -  Currently receiving treatment in another investigational device or drug study or less\n             than 30 days since ending treatment on another investigational device or drug study.\n             Other investigational procedures while participating in this study are excluded.\n\n        Inclusion and Exclusion Criteria - Part 2 Inclusion Criteria - Part 2\n\n          -  MRD-positive assessment (by NGS analysis) at enrollment or at any time during the\n             run-in 1 period\n\n          -  PET-CT negative (defined by Deauville criteria ? 3) at run-in 2 performed ? 3 weeks\n             from MRD-positive assessment at run-in 1. Historical PET-CT are allowed if performed ?\n             6 weeks from day 1 (first dose of blinatumomab) and subject has no clinical signs or\n             symptoms suggestive of disease progression (eg, increase in lactate dehydrogenase\n             [LDH] not otherwise explained)\n\n          -  Adequate organ function determined ? 2 week prior to treatment assignment with\n             blinatumomab as follows:\n\n               -  Hematological:\n\n        ANC ? 1.0 x 109/L Hemoglobin ? 8 g/L Platelet count ? 75 x 109/L o Renal: Creatinine\n        clearance ? 50 mL/min Cockcroft-Gault equation\n\n        o Hepatic: AST and ALT < 3 x ULN Total bilirubin < 2 x ULN (unless Gilbert's Disease or if\n        liver involvement with lymphoma)\n\n        Exclusion Criteria - Part 2 Subject has active infection requiring systemic therapy Any\n        change in the part 1 eligibility criteria during the run-in period.\n\n        Other Exclusion Criteria may apply
Presence of N2-3 or M1 disease
Have evidence of radiographic disease progression with scan documenting progression occurring within 8 weeks of signing informed consent
SSA therapy is recommended by physician for disease management, and has not yet begun
Untreated or poorly controlled gastro-esophageal reflux disease
Patients with evidence of tumor in the brainstem, cerebellum, optic apparatus, or spinal cord, radiological evidence of actively growing multifocal disease, or leptomeningeal disease
Disease status defined as refractory to or relapsed after >=1 prior treatment lines.
History or presence of clinically relevant non-lymphoma central nervous system pathology, including seizures that are uncontrolled on anticonvulsant therapy (>= 1 seizure in the last year), paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson disease, cerebellar disease, or psychosis
Confirmed diagnosis of sickle cell disease by hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) [performed locally]. All sickle cell disease genotypes are eligible.
Patients whose disease is refractory (defined as evidence of disease progression while on drug or within 3 months of its discontinuation) to more than 2 lines of chemotherapy given for CRPC. Any number of chemotherapies to which the patient’s disease is not refractory are allowed, as long as time on treatment did not exceed 6 months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment).
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator.
Patients with known Gilbert’s disease
Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
Life-threatening visceral disease or other severe concurrent disease
Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, or afatinib.
Inclusion Criteria:\n\n          -  Signed a written informed consent form(s).\n\n          -  ECOG performance status 0-1.\n\n          -  Women of childbearing potential must use adequate contraception (hormonal or barrier\n             method of birth control; abstinence).\n\n        HLA INCLUSION\n\n        • Pathologically confirmed advanced/metastatic solid tumors such as one of the following\n        indications:\n\n          -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent NSCLC\n\n          -  Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC (oral\n             cavity, pharynx, larynx)\n\n        MAIN SCREENING & LEUKAPHERESIS INCLUSION\n\n          -  Pathologically confirmed advanced/metastatic solid tumors such as one of the following\n             indications:\n\n               -  Pathologically confirmed diagnosis of stage IIIB/IV recurrent NSCLC\n\n               -  Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC\n                  (oral cavity, pharynx, larynx)\n\n          -  HLA phenotype positive NOTE: Patients who were previously HLA-typed for participation\n             in other Immatics' sponsored clinical trials and were HLA phenotype positive may enter\n             IMA201-101 main screening\n\n          -  Patient's tumor must express specified biomarkers. NOTE: Patients who were previously\n             screened for participation in other Immatics' sponsored clinical trials and whose\n             biomarkers are positive for IMA201-101 based on IMA_Detect may enter IMA201-101\n             screening\n\n          -  Recommended acceptable organ and marrow function, defined per protocol\n\n          -  Measurable disease\n\n          -  At least one lesion (metastasis or primary tumor) being considered accessible for a\n             biopsy.\n\n          -  Adequate hepatic function, as defined per protocol\n\n          -  Serum creatinine within 1.5 x normal range for age OR creatinine clearance with a\n             recommended GFR ? 50 mL/min/1.73m2.\n\n          -  Adequate pulmonary function, defined per protocol and oxygen saturation >92% on room\n             air.\n\n          -  Acceptable coagulation status: INR ?2.0 x ULN and PTT ?2.0 x ULN.\n\n          -  Confirmed availability of production capacities for the patient's ACTengine IMA201\n             product prior to the leukapheresis.\n\n        TREATMENT INCLUSION:\n\n        Patients may enter the treatment phase if:\n\n          -  Disease recurs/progresses\n\n          -  Disease becomes refractory or previous anti-cancer treatment is no longer warranted\n\n               -  Available IMA201 T-cell product that was produced for the patient and passed all\n                  release tests.\n\n               -  Adequate hepatic function per protocol.\n\n               -  Serum creatinine within 1.5 x normal range for age or creatinine clearance with a\n                  recommended GFR ? 50 mL/min/1.73m2.\n\n               -  Measurable disease\n\n               -  Male patients must agree to use effective contraception or be abstinent while on\n                  study and for 90 days after the infusion of IMA201.\n\n        Exclusion Criteria:\n\n        • Pregnant or is breastfeeding.\n\n        HLA EXCLUSION:\n\n          -  History of other malignancies (except for adequately treated basal or squamous cell\n             carcinoma or carcinoma in situ) within the last 3 years.\n\n          -  Serious autoimmune disease\n\n        MAIN SCREENING EXCLUSION:\n\n          -  Any condition contraindicating leukapheresis.\n\n          -  Brain metastases.\n\n          -  HIV infection, active Hepatitis B or C infection\n\n          -  Concomitant therapy indicated with any of the following: interferons or other\n             non-study immunotherapy regimens; immunosuppressive agents; other investigational\n             therapies; or chronic use of systemic corticosteroids.\n\n          -  Severe immune-related toxicities related to checkpoint inhibitors defined per\n             protocol.\n\n          -  Cardiac conditions per protocol\n\n          -  Prior stem cell transplantation or solid organ transplantation.\n\n          -  Concurrent severe and/or uncontrolled medical disease that could compromise\n             participation in the study\n\n          -  Active diverticulitis, intra-abdominal abscess or gastrointestinal (GI) obstruction.\n\n          -  History of other malignancies (except for adequately treated basal or squamous cell\n             carcinoma or carcinoma in situ) within the last 3 years.\n\n          -  Serious autoimmune disease\n\n          -  History of hypersensitivity to cyclophosphamide, fludarabine or IL-2.\n\n          -  History of or current immunodeficiency disease or prior treatment compromising immune\n             function\n\n          -  Patients with active pneumonitis.\n\n          -  Investigator's judgment\n\n        TREATMENT EXCLUSION\n\n          -  Received chemotherapy, surgery, or radiotherapy (for therapeutic purposes) within 3\n             weeks (4 weeks for monoclonal antibodies or investigational drugs, 1 week for tyrosine\n             kinase inhibitor (TKI) (e.g. erlotinib, gefitinib) or the patient has not recovered\n             (from grade ?2 side effects of the previous therapy) prior to lymphodepletion regimen.\n\n          -  Active pneumonitis.\n\n          -  Patient unable to tolerate lymphodepletion, low-dose IL-2 and/or ACTengine IMA201\n             treatment.\n\n          -  Severe immune-related toxicities related to checkpoint inhibitors defined per\n             protocol.\n\n          -  Investigator's judgment
Investigator determined assessment of disease progression after treatment with pembrolizumab monotherapy, OR
Has disease that is suitable for local therapy administered with curative intent
Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
Documented failure to achieve at least PR with, or documented disease progression after, the most recent treatment regimen.
Must have measureable disease as per RECIST Version 1.1 or RANO (for GBM).
Absolute neutrophil count (ANC) >= 750/uL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia >= grade 3 if it is due to disease, based on the results of bone marrow studies
Platelet count >= 50,000/uL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia >= grade 3 if it is due to disease, based on the results of bone marrow studies
Absolute lymphocyte count >= 150/uL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia >= grade 3 if it is due to disease, based on the results of bone marrow studies
DISEASE SPECIFIC EXPANSION COHORTS: Prior receipt of docetaxel is not permitted
Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease
Disease outside of the peritoneal cavity
Pathologically confirmed stage IV unresectable relapsed, or unresectable refractory abdominal neuroendocrine tumor from the last biopsy available which may be the initial diagnostic biopsy; relapsed disease is defined as progressive disease following systematic therapy with lanreotide or equivalent and either sunitinib or everolimus or both; refractory disease is defined as disease not responding to or having progressed within 1 month of the last dose of most recent systemic therapy to include lanreotide or an analog and either sunitinib or everolimus; (Note, small cell carcinoma and large cell undifferentiated neuroendocrine tumors will be excluded from this trial)
Any other severe concurrent disease, or history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that, in the investigator’s opinion, may place the patient at undue risk to undergo therapy with ibrutinib.
Patients tumors must be documented to be microsatellite-stable (MSS) either by genetic analysis or immunohistochemistry OR microsatellite-high with documented disease progression following anti-PD1/PDL1 therapy
Progressive disease by RECIST 1.1 with or without symptoms within the last 12 months; NOTE: untreated patients with existing histologic diagnoses are eligible if progression can be demonstrated
Must have presence of SSTR+ disease as documented by positive Ga-68-DOTATATE PET scan within 26 weeks of anticipated treatment\r\n* NOTE:\r\n** Positivity of Ga-68-DOTATATE PET scan defined as having at least one lesion that is >= 10 mm in diameter with uptake that is higher than or equal to liver and is qualitatively higher and distinguishable from background activity\r\n** Measurable disease as defined by RECIST 1.1
Patients with extrahepatic disease are eligible
Patients with asymptomatic leptomeningeal disease are eligible for participation in this trial; however, patients who had progression of leptomeningeal disease on alectinib will be required to undergo CNS radiation to meet eligibility
Active inflammatory gastrointestinal disease or previous gastric resection or lap band
Previously treated ASCT naive MM patients, currently with relapsed or refractory disease who are being considered for single ASCT for relapsed disease; patients must be eligible to undergo a stem cell transplant as per institutional criteria for selection at the time of registration
Patients must have disease that has relapsed after carfilzomib therapy, with progressive disease (PD) being defined as an increase of 25% from the lowest response value in any one or more of the following:\r\n* Serum M-component (the absolute increase must be >= 0.5 g/dL) and/or\r\n* Urine M-component (the absolute increase must be >= 200 mg/24 hours) and/or\r\n* Only in patients without a measurable serum and urine M protein level: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase) must be > 10 mg/dL\r\n* Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas\r\n* Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder\r\nPatients with relapsed disease will be considered to be those who have had progression, as defined above, off of any therapy, and who completed their therapy more than 60 days prior to the finding of progression; patients with relapsed and refractory disease will be considered to be those who have had progression, as defined above, while still on their last line of therapy, or who progressed within 60 days of finishing their most recent therapy
Patients with evidence of large B cell transformation (transformed disease) are not eligible; if in the opinion of the investigator there is high suspicion of transformed disease based on imaging (eg high standardized uptake value [SUV] uptake > 10 on the PET scan) and a biopsy of the suspected site is not feasible, then those patients are not eligible
The presence of disease that can be biopsied for research purposes is not an inclusion criterion
Any cancer-related therapy for the current disease within 2 weeks of screening (all supportive care measures are allowed)
Patients who have received previous treatment with T-DM1 and had systemic progression of disease while on it, are ineligible; patients receiving treatment with TDM1 whose only site of disease progression was brain are allowed to enroll in this trial
biopsy-proven refractory disease after frontline chemo-immunotherapy
for subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
Has disease that is suitable for local therapy administered with curative intent.
Evaluation by the treating medical oncologist (or if systemic therapy is being given outside Stanford, by the Stanford consulting medical oncologist) must show:\r\n* The patient is expected to continue on immunotherapy for at least three more months\r\n* Imaging must show response, stable disease, or modest progression\r\n* If there is modest progression, the patient must be clinically stable in terms of performance status and overall disease-related symptoms
Patients with active extramedullary disease.
Patients with leptomeningeal disease
Patients must have evidence of progressive disease
Leptomeningeal disease
Patients with diffuse subependymal or cerebrospinal fluid (CSF) disease
Disease that can be encompassed within a radical radiotherapy treatment volume
Have relapsed or refractory disease after at least 1 prior regimen, including: \r\n* Recurrence of disease after a documented complete response (CR) \r\n* Progression of disease after a partial response (PR) to the prior regimen \r\n* Partial response (PR), stable disease (SD) or progressive disease (PD) at the completion of the prior treatment regimen; if a patient has PR to prior regimen without PD, there must be biopsy-proven residual disease that is measurable
Symptomatic or untreated leptomeningeal disease
Soft tissue disease progression as defined by RECIST 1.1.
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator.
Patients must have evidence of disease progression and cannot be a candidate for surgical treatment or radiation\r\n* NOTE: Disease progression is defined as one of the following occurring within the 6 months prior to study entry:\r\n** At least a 20% increase in radiologically or clinically measurable lesions\r\n** Appearance of any new lesions or\r\n** Symptomatic and/or deterioration in clinical status
Incurable disease defined by the presence of metastases to other organs (stage IV) or disease beyond regional lymph nodes who have already received chemoradiation therapy, or have been assessed by Radiation Oncology consultation as not being candidates for chemoradiation therapy; dysphagia grade >= 3 to tumor obstruction
Leptomeningeal disease
Patients who were previously exposed to zydelig and experienced progression of disease
Subject meets disease-specific requirements per protocol
Distant metastases (M1 disease)
Histologically proven adrenocortical carcinoma (ACC) with the majority of disease confined to the peritoneal cavity and resectable or amenable to radiofrequency ablation; or disease that in the opinion of the investigators can be managed medically or surgically and does not present an immediate threat to the patient’s life
All disease should be deemed resectable based on imaging studies e.g.:\r\n* Hepatic metastases (unilateral or bilateral =< 5 lesions, =< 15 cm total diameter)\r\n** Note: Hepatic lesions must be amenable to complete resection\r\n* Primary peritoneal metastases (small disease load =< P2 disease) without intestinal obstruction\r\n* Lung metastases (=< 3 unilateral/bilateral, 9 cm total diameter)\r\n** Note: lung lesions must be amenable to complete resection\r\n* Note: Patients with both pulmonary and hepatic metastases will be enrolled at the discretion of the principal investigator (PI)\r\n* Note: In situations where resection to completeness of cytoreduction score (CC) 0 or 1 is uncertain, patients may undergo diagnostic laparoscopy prior to enrollment to determine feasibility of resection
Patients with extramedullary disease as their sole site of relapsed AML.
Patients with any high-risk features will also be eligible, including those who:\r\n* Fail to achieve complete remission with initial combination chemotherapy\r\n* Have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass >= 5 cm or other residual mass >= 10 cm accompanied by other features of persisting disease (e.g., positron emission tomography [PET] scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy
Residual areas of limited disease should be considered for radiotherapy after and not prior to transplantation
Patients who have undergone resection of primary disease.
For patients with refractory disease they must be at least 4 weeks out from most recent therapeutic intervention
Patients must have a histologically or cytologically confirmed measurable GIST without platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) or KIT proto-oncogene receptor tyrosine kinase (KIT) mutations; GIST may be newly diagnosed or recurrent provided that it meets criteria for progressive or metastatic disease; metastatic disease refers to disease outside the gastrointestinal (GI) tract, not simply a multifocal primary tumor; testing performed by the Laboratory of Pathology, National Cancer Institute (NCI), unless previously conducted by a CLIA/College of American Pathologists (CAP) external laboratory; analysis will include evaluation of 4 exons of KIT (9, 11, 13, 17) and 3 exons of PDGFRA (12, 14, 18)
Progressive disease: GIST has demonstrated progression as defined by RECIST v1.1 within the past 12 months; patients whose tumors do not meet this criterion, and have a diagnosis of NF1, may enroll on the NF1 natural history study
Presence of radiographically evaluable disease
Unequivocal demonstration of distant metastases (M1 disease)
(For cohort A): No limit on prior therapies for metastatic disease. (Relapse of disease within 6 months of adjuvant or neoadjuvant chemotherapy is considered 1 line of therapy for metastatic disease). (For cohort B): received at least one dose of an anthracycline-based NACT. Patients are eligible if therapy was discontinued due to disease progression or therapy intolerance. Patients with disease progression on anthracycline-based therapy should be evaluated by the surgical team. If the patient is deemed inoperable at the time of evaluation, the patient may continue to undergo protocol therapy with a goal of reduction in tumor size to become operable. If the patient is deemed at high risk of becoming inoperable by the surgical team based upon tumor size or location, the patient will be considered ineligible for study and will be recommended to go to surgery
New or increasing non-bone disease (RECIST 1.1 criteria);
Radiographic or clinical disease recurrence or progression during or after the last line of systemic therapy
Patients with a diagnosis of CD22-positive acute lymphoblastic leukemia (ALL) based on local immunophenotyping and histopathology who have:\r\n* Refractory disease, defined as disease progression or no response while receiving their most recent prior anti-cancer therapy,\r\n* Relapsed disease, defined as response to their most recent prior anti-cancer therapy with subsequent relapse
Relapsed disease after at least 2 lines of therapy
Disease must be refractory to or intolerant of at least first-line chemotherapy which contains 5-fluorouracil or gemcitabine
Advanced localized disease not suitable for local primary surgical intervention with curative intent (radiotherapy, cryotherapy, or high frequency ultrasound are allowed after 2 months of androgen deprivation therapy);
Has an active concurrent malignancy/life-threatening disease. If there is a history of prior malignancies/life-threatening diseases, the subject is to be disease free for at least 5 years. Subjects with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. Subjects will not be excluded for recurrent NMIBC, basal or squamous cell skin cancers, or noninvasive cancer of the cervix.
Patients with inoperable conditions with resectable disease (T1-2NoMo)
All malignant disease must be able to be encompassed within a single irradiation field
All patients must have radiographically assessable disease
Chemotherapy (chemo)-resistant (defined by stable disease [SD] or progressive disease [PD] to most recent chemo regimen)
Clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis
Patients must have evaluable disease on imaging
Subjects must have measurable disease (at least one target lesion) as defined by RECIST 1.1; target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment
Gross total excision of both the primary and nodal disease
Has unresectable disease or is medically inoperable
Disease not amenable to curative intent treatment (primarily surgery) and in addition has shown either clinical or radiographic progression on all available therapies known to confer clinical benefit
Radiographic progressive disease, irrespective of PSA changes, after receiving at least 4 cycles of docetaxel or cabazitaxel
Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord, tumors extending into or crossing the corpus callosum, intraventricular tumors, pineal tumors, pituitary tumors, radiological evidence of active (growing) multifocal disease, leptomeningeal disease, or other locations at the discretion of the treating neurosurgeon
Progressive disease, both docetaxel naive and docetaxel treated.
Male or female study participants with sickle cell disease
Chemotherapy refractory disease in aggressive NHL is defined as\r\n* Stable disease of =< 12 months or progressive disease as best response to most recent chemotherapy containing regimen\r\n* Disease progression or recurrence =< 12 months of prior autologous stem cell transplantation (SCT)
Visible additional disease that suggests a greater than T2 malignant melanoma
Patients must have progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy; for patients enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan; if the comparison scan is not available, the baseline scan report must reference the previous scan to document progression
Patients must have measurable disease by Response Assessment in Neuro-Oncology (RANO) 2010 criteria at the time of registration (pre-operative)
Meets one of the following disease criteria:\r\n* Multiple myeloma (MM) meeting one of the following:\r\n** Relapsed/refractory disease after two lines of therapies, including a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) and an immunomodulatory drug (thalidomide, lenalidomide or pomalidomide)\r\n** Relapsed disease between 2-18 months of 1st autologous stem cell transplantation\r\n** Relapsed disease at least 4 months after allogeneic stem cell transplantation with no evidence of active graft versus host disease AND with measurable disease defined as serum IgG, A, M M-protein >= 0.5 g/dL or serum IgD M-protein >= 0.5 g/dL, or urine M-protein >= 200 mg/24 hours AND at least at least 4 weeks since plasmapheresis\r\n* CD20-positive B-cell non-Hodgkin lymphoma (NHL)\r\n** CD20 expression confirmed by flow cytometry or immunohistochemistry and meeting one or more of the following:\r\n** Evidence of relapsed/refractory disease that has failed conventional therapy\r\n** Relapsed disease at least 60 days after autologous stem cell transplantation\r\n** Relapsed disease at least 4 months after allogeneic stem cell transplantation with no evidence of active graft versus host disease\r\n** Has measurable disease > 1.5 cm in diameter
Relapsed or refractory disease after first-line chemoimmunotherapy
Stable disease (SD) as best response after at least 4 cycles of first-line therapy
Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ? 12 months from initiation of therapy
Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram [ECG] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
Have CMV tissue invasive disease as assessed by the investigator at the time of screening and randomization at Visit 2/Day 0.
MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization [FISH], or PCR) with relapsed or refractory disease after at least 1 prior line of MCL therapy
PET-positive disease by Lugano classification
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
Patients with Gilbert's disease.
Disease progression by IWG Working Group or ICML criteria since last therapy
Patients with SSc as defined by the American College of Rheumatology with diffuse cutaneous disease (except Group 5) at risk of disease progression
Patients must have failed a prior >= 4-mponth course of either MMF/Myfortic or cyclophosphamide before being eligible for the study (determined at >= 1 week before start of mobilization); “failure” is defined as evidence of disease progression or absence of improvement; the response prior to MMF of cyclophosphamide will be assessed by the participating site study rheumatologist
GROUP 1: \r\n* Patients must have 1) both a and b below; and 2) either c, or d\r\n** a) Diffuse cutaneous scleroderma as defined by skin thickening proximal to the elbows and knees and/or involving the torso in addition to distal extremity involvement; a skin score will be obtained but not used to determine eligibility\r\n** b) Duration of systemic sclerosis =< 7 years from the onset of first non-Raynaud's symptom; for those patients with disease activity between 5-7 years from the onset of first non-Raynaud's symptom, recent progression or activity of disease must be documented\r\n** c) Presence of SSc-related pulmonary disease with forced vital capacity (FVC) < 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide (DLCO) < 70% of predicted AND evidence of alveolitis or SSc-related interstitial lung disease by high-resolution chest computed tomography (CT) scan and/or by bronchoalveolar lavage (BAL) (interstitial lung disease may be nonspecific interstitial pneumonia [NSIP] or usual interstitial pneumonia [UIP]; a bronchoalveolar lavage [BAL] should be done to confirm the findings of alveolitis only if the high resolution CT scan [HRCT] fails to show findings typically associated with systemic sclerosis changes [ground glass NSIP, UIP, SSc related interstitial lung disease]); alveolitis by BAL cell count will be defined based on a BAL cell differential count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe\r\n** d) History of SSc-related renal disease that may not be active at the time of screening; stable serum creatinine must be documented for a minimum of 3 months post-renal crisis at the time of the baseline visit; history of scleroderma hypertensive renal crisis is included in this criterion and is defined as follows:\r\n*** History of new-onset hypertension based on any of the following (measurements must be repeated and confirmed at least 2 hours apart within 3 days of first event-associated observation, with a change from baseline):\r\n**** Systolic blood pressure (SBP) >= 140 mmHg\r\n**** Diastolic blood pressure (DBP) >= 90 mmHg\r\n**** Rise in SBP >= 30 mmHg compared to baseline\r\n**** Rise in DBP >= 20 mmHg compared to baseline\r\n***AND one of the following 5 laboratory criteria: \r\n**** Increase of >= 50 % above baseline in serum creatinine\r\n***** Proteinuria: >= 2+ by dipstick confirmed by protein:creatinine ratio > 2.5\r\n***** Hematuria: >= 2+ by dipstick or > 10 red blood cell (RBC)s/hematopoietic-promoting factor (HPF) (without menstruation)\r\n***** Thrombocytopenia: < 100,000 platelets/mm^3\r\n***** Hemolysis: by blood smear or increased reticulocyte count\r\n*** The above definition of SSc hypertensive renal crisis is independent of whether concomitant anti-hypertensive medications are used\r\n*** Subjects who present with solely skin and renal disease in the absence of other organ involvement, except classic SSc renal crisis as described above and including non-hypertensive renal crisis, must see a nephrologist to confirm that their renal disease is secondary to only SSc\r\n*** Note: Subjects may be re-screened if they fail to meet inclusion criteria on initial evaluation
GROUP 2:\r\n* Progressive pulmonary disease as defined by a decrease in the FVC or DLCO-adjusted by 10 or 15 percent or greater, respectively, from a prior FVC or DLCO-adjusted in the previous 18-month period\r\n* Patients will have diffuse cutaneous disease and may have both FVC and DLCOcorr >= 70% at screening for the study\r\n* Patients must also have evidence of alveolitis as defined by abnormal chest computed tomography (CT) or bronchoalveolar lavage (BAL)
GROUP 3: Diffuse scleroderma with disease duration =< 2 years since development of first sign of skin thickening plus modified Rodnan skin score >= 25 plus either\r\n* Erythrocyte sedimentation rate (ESR) > 25 mm/1st hour and/or hemoglobin (Hb) < 11 g/dL, not explained by causes other than active scleroderma\r\n* Lung involvement (either FVC or DLCO < 80% and evidence of interstitial lung disease by CT scan or alveolitis by BAL)
GROUP 4: Diffuse scleroderma with disease duration =< 2 years and skin score >= 30
Patient must have disease amenable to biopsy and must agree to have one baseline biopsy
Patients who have noncanonical DNA repair defects and extensive visceral disease or symptomatic bone disease requiring urgent tumor response
a) Intraocular PCNSL without evidence of brain disease b) PCNSL patients who cannot undergo MRI assessments c) PCNSL patients with systemic disease
Has presence of diffuse leptomeningeal disease or extracranial disease
Disease status: Subjects must have measurable or evaluable disease, by RECIST v1.1 ± Curie Scale Criteria or RANO/RANO-BM
Identified as having visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis; visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease
Patients with thromboembolic disease and on anticoagulation
Have evaluable disease
Patients with Stage IIIB/IV squamous or non-squamous NSCLC (American Joint Committee on Cancer 7th Edition Staging) who have had prior treatment with nivolumab or pembrolizumab will be enrolled in one of 3 parallel cohorts based on the following:\r\n* Cohort 1: patient with progressive disease on nivolumab or pembrolizumab as the BOR; progressive disease must be confirmed with a confirmatory scan ? 4 weeks after the 1st documented date of progression\r\n* Cohort 2: patients with stable disease as the BOR on a minimum of 12 weeks of therapy with nivolumab or pembrolizumab\r\n* Cohort 3: patients with partial or complete response as the BOR, followed by progressive disease, on nivolumab or pembrolizumab; a confirmatory scan at the time of disease progression must be performed ? 4 weeks after the 1st documented date of progression
Relapsed/refractory disease
Patients underwent >= 1 prior chemotherapy-based or immunotherapy-based regimen or targeted therapy (e.g., inhibitors of BTK, PI3K etc.) administered for >= 2 cycles, and have had either documented disease progression or no response (stable disease) to the most recent treatment regimen
Patients with CLL/SLL must demonstrate active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment:\r\n* A minimum of any one of the following constitutional symptoms:\r\n** Unintentional weight loss > 10% within the previous 6 months prior to screening\r\n** Extreme fatigue (unable to work or perform usual activities)\r\n** Fevers of greater than 100.5 Fahrenheit (F) for >= 2 weeks without evidence of infection\r\n** Night sweats without evidence of infection\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia\r\n* Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly\r\n* Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy\r\n* Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months\r\n* Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids
Patients diagnosed with acute myeloid leukemia (AML) by World Health Organization (WHO) classification, meeting one of following criteria:\r\n* Age 60 or older, newly diagnosed, untreated, who are unwilling to undergo or not candidates for conventional induction chemotherapy with cytarabine/anthracyclines\r\n* Age 60 or older with relapsed or refractory disease\r\n* Younger adult patients with previously untreated high-risk disease (complex karyotype, inv[3] or t[3;3], t[6;9], monosomal karyotype, therapy-related and secondary disease) that are unwilling to undergo or not candidates for conventional induction chemotherapy with cytarabine/anthracyclines and/or allogeneic stem cell transplantation\r\n* Younger patients with refractory/relapsed AML who are otherwise not candidates for allogeneic stem cell transplantation\r\n* Patients with extramedullary disease who meet one of the above criteria may be included
Patients may take steroids for disease control up to 24 hours prior to study enrollment
Patients who are to undergo definitive chemoradiation must have clinically or radiographically evident measurable disease at the primary site and/or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal disease is permitted.
Progression of disease by radiographic imaging (10% increase in size by RECIST version [v]1.1 within 6 months of registration) or presence of new lesions
Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord, radiological evidence of active (growing) multifocal disease, subependymal or leptomeningeal disease
Documented progression of disease on at least one 5-FU-based regimen and at least one GEM-based regimen for metastatic disease (progression during or within 3 months of the completion of adjuvant therapy is acceptable)
Active peptic ulcer disease even if asymptomatic
with relapsed or refractory disease without established alternative therapy or
No evidence of disease-related symptoms and extramedullary disease, including the liver and spleen
Acute or chronic pancreatic disease within the last year prior to enrollment
Subjects must have a histologically determined B cell NHL subtype as defined in the bullets below. In addition, they must have disease that is primary refractory after initial therapy or have relapsed disease.
Have evaluable disease
No more than three progressive sites of disease, with at least one of the disease sites to be deemed suitable for treatment with MRI-guided, online adaptive SBRT to the non-liver abdomen as per radiation oncology evaluation
Clinical evidence of progression of disease > 20% in the breast or new evidence of nodal metastases
Neurological disorder (Parkinson’s disease, dementia, multiple sclerosis)
Patient must have disease progression with abiraterone treatment
Requirement for therapy of the hematological malignancy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
Paget’s disease of the nipple
In the opinion of the investigator and confirmed by the Millennium medical monitor, the participant may continue to benefit from treatment with ixazomib (eg, response to therapy or stable disease without evidence of disease progression).
Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 2 consecutive documented, negative spinal fluid assessment prior to Screening
Radiographic disease recurrence or progression during or after the last line of chemotherapy
Have previously untreated localized gastric or gastroesophageal (GE) junction adenocarcinoma as defined by T2 or greater primary lesion or the presence of any positive nodes-N+(clinical nodes) without evidence of metastatic disease
Evidence of evaluable disease
Failure of first-line anti-cancer therapy with an oxaliplatin and bevacizumab-based regimen (either radiological documentation of disease progression or due to toxicity) or subsequent relapse of disease following first-line therapy; patients relapsing within 12 months of completing adjuvant fluorouracil, leucovorin calcium, oxaliplatin (FOLFOX) will also be considered eligible
Leptomeningeal disease
Medically fit and willing to undergo resection of disease
Active peptic ulcer disease for lesions within 5 cm of the stomach
Evidence of leptomeningeal disease
History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis
Current autoimmune disease or history of autoimmune disease with potential CNS involvement; auto-immune disease with possible CNS consequences/manifestations such as such as epilepsy, paresis, aphasia, stroke, dementia, Parkinson’s disease, cerebellar disease, or psychosis
Radiographic or cytologic evidence of leptomeningeal or multifocal disease at any time prior to study entry
Patients must have biopsiable disease at the time of enrollment as biopsies after progression are required for participation
No visceral crisis: Visceral crisis is moderate-to severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
Development of visceral crisis since pre-registration.\r\n* NOTE: Visceral crisis is moderate-to-severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease.
Patients with progressive disease at time of transplant
Subjects must have received 1 or more prior therapies for this disease and have had stable disease or progressive disease based upon the criteria from the Revised Response Criteria for Malignant Lymphoma, or intolerable toxicities precluding further therapy with a prior regimen
Subjects with leptomeningeal disease are excluded
Known evidence of active cerebral/meningeal CLL; patients may have a history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease)
Prior resection of extra-hepatic metastatic disease allowed if completed more than 12 months previous to study enrollment and no new extra-hepatic disease has been found
A histologically or pathologically confirmed diagnosis of AML based on WHO classification with or without extramedullary disease except for central nervous system disease.
Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
Progressive disease despite ongoing androgen deprivation or chemotherapy. Progressive disease is defined by 1 or more of the following criteria:
Any of the disease stages listed below\r\n* Stage IB disease that meets ALL of the following criteria:\r\n** Plaque disease (ie,T2b staging)\r\n** Diffuse skin involvement with indication for TSEB (plaque disease with or without patches)\r\n** Not appropriate for treatment with focal therapies\r\n** One prior course of low-dose TSEB or one prior course of systemic chemotherapy regimens (excluding brentuximab)\r\n* Stage IIA, IIB, or IIIA that meets ONE or BOTH of the following criteria:\r\n** Patient is a candidate for treatment with low-dose TSEB\r\n** Patient is a candidate for systemic therapy\r\n* IIIB or IVA disease requiring systemic therapy\r\n* Transformed cutaneous T-cell lymphoma (CTCL)
Disease must be technically amenable to transhepatic arterial chemoembolization (TACE) (HCC patients only), radiofrequency ablation (RFA), or cryoablation; each case will be discussed at gastrointestinal (GI) tumor board with interventional radiology; patients must have evaluable disease
Presence of leptomeningeal disease
Patients must have potentially curable disease
Have had disease progression, be refractory or intolerant to no more than 2 prior systemic regimens.
Patients must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging
Patients with T4 disease
Patients with N3 disease
Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 1 documented, negative spinal fluid assessment within 28 days prior to Screening
Subjects must have received frontline standard therapy for high-risk neuroblastoma and meet one of the following three conditions for recurrent/progressive, refractory, or persistent disease\r\n* Recurrent/progressive disease at any time prior to enrollment (regardless of overall response to frontline therapy)\r\n* Refractory disease: persistent sites of disease after achieving a best overall response of stable disease to frontline therapy after a minimum of 4 cycles of induction therapy AND patient has never had recurrent/progressive disease\r\n* Persistent disease: persistent sites of disease after achieving a best overall response of partial response to frontline therapy after a minimum of 4 cycles of induction therapy AND patient has never had recurrent/progressive disease
Subject’s current disease state must be one for which there is no known curative therapy
Hepatitis B or C seropositivity with evidence of ongoing liver damage; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
PHASE II SCLC: Patients could have received any number of therapies for relapsed or progressive disease, including re-treatment with original frontline regimen; a minimum of 2 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation; in addition, recovery to grade =< 1 from all reversible toxicities related to prior therapy is required at study entry; no previous irradiation to the site of measurable or evaluable disease, unless that site had subsequent evidence of progression
Presence of MRD (defined as < 5% blasts in the bone marrow by morphologic assessment and no clinically-apparent extramedullary disease but with quantifiably-measurable disease as assessed by either MFC or PCR) under any of the following circumstances:\r\n* MRD persistence >= 11 weeks after the start of initial therapy\r\n* MRD persistence >= 2 weeks after the start of salvage therapy, or \r\n* MRD reappearance at any time
Concurrent palliative radiotherapy for local pain-control may be allowed provided the subject completes the first cycle of treatment, does not meet criteria of progressive disease, and treated lesions will not be included in the target/non-target lesion assessment.
In patients with suspected leptomeningeal disease, the diagnosis of leptomeningeal disease should be confirmed by the presence of neurological or imaging signs and/or positive cerebrospinal fluid (CSF) cytology
Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
Diagnosis of leptomeningeal disease
Prior brentuximab vedotin is allowed provided that patients were not refractory (defined as developing progressive disease while on treatment or progressed within 3 months of finished last dose of brentuximab vedotin)
Known cerebral/meningeal disease
Patients must have achieved at least partial response (PR) prior to autologous HCT and must not have progressive disease (PD) prior to the initiation of maintenance therapy
Additional criteria for bulky disease (lymphomas):\r\n*If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately)\r\n*If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
Have biopsiable disease; subjects must have at least one lesion amenable to biopsy; tumor lesions used for biopsy should not be lesions used as RECIST target lesions; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease
Patients must ? 12 weeks from radiotherapy, to minimize the potential for magnetic resonance imaging (MRI) changes related to treatment (pseudo progression) that might be misdiagnosed as true progression of disease, unless the patient fulfills criteria for early progressive disease by RANO.
Within 12 weeks of chemoradiation unless the patient fulfills criteria for early progressive disease by RANO
Evidence of leptomeningeal spread of disease
History of Wilson’s disease or family member with Wilson’s disease
Inoperable disease because of patient refusal, neurosurgical evaluation, or any other medical reasons
Patients whose disease is refractory (defined as evidence of disease progression while on drug or within 3 months of its discontinuation) to more than 2 lines of chemotherapy; any number of chemotherapies to which the patient’s disease is not refractory are allowed, as long as time on treatment did not exceed 6 months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment)
Patient must have imaging findings within the last 3 months consistent with recurrent disease in the brain; pathologic diagnosis of recurrence is not required
Has known carcinomatous meningitis (also known as leptomeningeal disease)
PRIOR TO CELL PROCUREMENT: CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30 cells); NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard
PRIOR TO LYMPHODEPLETION: CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to lymphodepletion); NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard
Patients must have measurable or evaluable disease; NOTE: All patients with greater than 10% abnormal CD4+ homogeneous CD3^low strongly CD25+ expressing cells, or greater than 5% Sezary/T-PLL cells, among the peripheral blood mononuclear cells (PBMCs) in the peripheral blood will be deemed to have evaluable disease
Paget’s disease of the nipple
AML patients: \r\n* Cytogenetics and molecular features consistent with adverse risk group;\r\n* Presence of minimal residual disease by multi-color flow cytometry or cytogenetics or molecular studies at the time of HSCT; \r\n* Presence of active disease defined as bone marrow blast count > 5% but less than =< 10% at the time of HSCT\r\n* Peripheral blood blast count =< 5% at HSCT
Presence of leptomeningeal disease
Disease-related exclusions
If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by infectious disease
Intermediate or high grade NHL, mantle cell NHL, and Hodgkin disease that is progressive on salvage therapy; stable disease is acceptable to move forward provided it is non-bulky
All patients should have either five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion; or other assessable disease
Group I: KS requiring systemic therapy (no prior therapy required) and:\r\n* Group I patients should have one or more of the following:\r\n** T1 KS, KS on skin sufficiently widespread that it is not amenable to local therapy, or KS affecting quality of life due to local symptoms or psychological distress\r\n** KS patients with an inadequate response to pomalidomide (either progressive disease or stable disease requiring additional therapy after 4 months)\r\n** KS patients with an inadequate response to liposomal doxorubicin, paclitaxel, or other systemic chemotherapy (either progressive disease or stable disease requiring additional therapy after 6 cycles)\r\n* Group I will exclude patients eligible for Group II (below); patients with a history of multicentric Castleman disease (MCD) in the absence of any active disease (as assessed by the PI) are eligible for Group I\r\n* A wash out period off treatment of 3 weeks will be required, except in the case of patients with progressive, severe disease in which delay of treatment cannot be justified (i.e. symptomatic pulmonary KS)
At least five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion; or other assessable disease
Patients with clinical evidence of disease beyond the uterus, including presence of suspicious aortic or inguinal nodes on imaging or clinical exam
Immunocompromised status due to:\r\n* Human immunodeficiency virus (HIV) positivity\r\n* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Graves disease; patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed\r\n* Other immunodeficiency diseases
Patients who have progressive disease or relapse (as defined by the IWCLL criteria) at or any time before registration on this study
Inclusion Criteria:\n\n        Subject must meet all of the following applicable inclusion criteria to participate in this\n        study:\n\n          -  Written informed consent and HIPAA authorization for release of protected health\n             information obtained from the subject prior to performing any protocol-related\n             procedures, including screening evaluations. NOTE: HIPAA authorization may be included\n             in the informed consent or obtained separately.\n\n          -  Age ? 18 years at the time of consent.\n\n          -  ECOG Performance Status of 0-1 within 28 days prior to registration for protocol\n             therapy.\n\n          -  Females of childbearing potential and males must be willing to use an effective method\n             of contraception (hormonal or barrier method of birth control; abstinence) from the\n             time consent is signed until 12 weeks after treatment discontinuation.\n\n          -  Females of childbearing potential must have a negative serum pregnancy test within 14\n             days prior to registration for protocol therapy. NOTE: Female subjects are considered\n             of child bearing potential unless they are surgically sterile (they have undergone a\n             hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are ?60\n             years old and naturally postmenopausal for at least 12 consecutive months.\n\n          -  Histological evidence of persistent residual esophageal adenocarcinoma including\n             gastroesophageal junction adenocarcinoma following definitive concurrent\n             chemoradiotherapy (carboplatin and paclitaxel or cisplatin and 5-FU) in the surgical\n             sample (esophagus or lymph node or both) obtained at the time of esophagectomy. NOTE:\n             Persistent residual disease is defined as follows (modified from College of American\n             Pathologists Guidelines):\n\n               -  No residual tumor (Grade 0, complete response, 0% tumor). This group will not be\n                  included in this study.\n\n               -  Marked response (Grade 1, 0-<10% residual tumor)\n\n               -  Moderate response (Grade 2, 10-50% residual tumor)\n\n               -  No definite response (Grade 3, >50% residual tumor)\n\n          -  Minimum of 1 month and maximum of 3 months from surgical resection with no evidence of\n             disease progression at the time of enrollment.\n\n          -  Must have adequately recovered from surgery as judged by the treating investigator.\n\n          -  Subject is willing and able to comply with the protocol for the duration of the study\n             including undergoing treatment and scheduled visits and examinations including follow\n             up.\n\n        Exclusion Criteria:\n\n        Subjects meeting any of the criteria below may not participate in the study:\n\n          -  Prior therapy with a PD-1, PD-L1, or CTLA-4 inhibitor or cancer-specific vaccine\n             therapy.\n\n          -  Evidence of active autoimmune disease requiring systemic treatment within preceding 3\n             months or a documented history of clinically severe autoimmune disease, or a syndrome\n             that requires systemic steroids or immunosuppressive agents. Exceptions to this rule\n             include vitiligo, resolved childhood asthma/atopy, requirement of intermittent\n             bronchodilators or local steroid injections, hypothyroidism stable on hormone\n             replacement, psoriasis not requiring systemic treatment (within the past 2 years),\n             Graves's disease and Sjogren's syndrome.\n\n          -  Prior malignancy is not allowed except for adequately treated basal cell or squamous\n             cell skin cancer, in situ cervical cancer, Gleason score ? 7 prostate cancers, or\n             other cancer for which the subject has been disease-free for at least 3 years.\n\n          -  Active or prior documented inflammatory bowel disease (e.g. Crohn's disease,\n             ulcerative colitis).\n\n          -  Presence of interstitial lung disease or history of pneumonitis requiring treatment\n             with corticosteroids.\n\n          -  Patients with diagnosis of primary immunodeficiency.\n\n          -  Patients receiving chronic systemic corticosteroid therapy or other immunosuppressive\n             therapy within 28 days prior to registration for protocol therapy. Exceptions include\n             intranasal and inhaled corticosteroids or systemic corticosteroids at physiological\n             doses, which are not to exceed 10 mg/day of prednisone, or an equivalent\n             corticosteroid.\n\n          -  History of allogeneic organ or stem cell transplant.\n\n          -  Receipt of live attenuated vaccine within 30 days prior to registration for protocol\n             therapy.\n\n          -  Mean QT interval corrected for heart rate (QTc) > 470 msec calculated from 3 ECGs by\n             Bazett's Correction.\n\n          -  Ventricular arrhythmias requiring medication(s).\n\n          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic\n             congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac\n             arrhythmia, active peptic ulcer disease or gastritis, or active bleeding diatheses.\n\n          -  History of psychiatric illness/social situations that would limit compliance with\n             study requirements or compromise the ability of the subject to give written informed\n             consent.\n\n          -  Known HIV infection or chronic hepatitis B or C.\n\n          -  Known history of previous clinical diagnosis of tuberculosis.\n\n          -  Clinically significant infections as judged by the treating investigator. Clinically\n             significant is defined as an active infection requiring IV antibiotics.\n\n          -  Because there is an unknown but potential risk for adverse events in nursing infants\n             secondary to treatment of the mother, breastfeeding should be discontinued. In\n             addition, breast milk cannot be stored for future use while the mother is being\n             treated on study.\n\n          -  Treatment with any investigational agent within 28 days prior to registration for\n             protocol therapy.\n\n          -  History of hypersensitivity to durvalumab or any excipient.\n\n          -  Any condition that, in the opinion of the investigator, would interfere with\n             evaluation of study treatment or interpretation of patient safety or study results.\n\n          -  Previous enrollment in the present study.
Patients must have progressed during or after first-line treatment for metastatic disease with oxaliplatin and fluoropyrimidines based chemotherapy (with failure within six months) or not be a candidate for oxaliplatin (i.e. neuropathy)
The predominant burden of disease lies in an arterial distribution which is accessible for transarterial chemoperfusion treatment
Multi-focal disease (unless pre-approved by principal investigator [PI])
If extrahepatic disease is present, it must be asymptomatic
Diagnosis of uveal melanoma with histological or cytological confirmed metastatic disease. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent therapy.
Malignant disease other than that being treated in this study.
N3 nodal disease
Disease is termed unresectable or the patient refuses resection
Significant auto-immune disease requiring hospitalization within the past two years or any history of life-threatening auto-immune disease
Evidence of disease by standard morphologic or by minimal residual disease (MRD) criteria
Symptomatic valvular heart disease
Chronic or current active infectious disease requiring systemic antibiotics, antifungals, or antivirals
Patients must have had front line therapy for their disease
For Part 2 and Part 3 of the study, patients with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment).
Evaluable disease
Lesions that are accessible for injection and electroporation, defined as cutaneous or subcutaneous disease.
No life threatening parenchymal disease or rapidly progressing disease warranting cytotoxic chemotherapy
Has primary refractory disease (this is, those whose tumors have progressed at the first restaging during first line therapy)
Evidence of progression of disease as defined by RECIST 1.1 (i.e. new disease sites or 20% growth of index lesions) within 6 months of registration
Subjects who experience a disease response per RECIST 1.1 criteria followed by subsequent progression will be required to have a post-treatment biopsy if feasible and safe
Fully resected disease at study entry (residual CIS acceptable)
Evidence of MM disease progression any time prior to enrollment; progression from smoldering/asymptomatic MM to symptomatic MM is not exclusionary
Diagnosis of widespread visceral and/or osseous metastatic disease based on clinical and radiographic evidence; (patients may continue on study if surgery shows a non-malignant process)
Invasion or ulceration of inguinal nodal disease into the overlying skin
Participants with LL must have radiographic evidence of disease
Must have evidence of either RECIST 1.1 defined disease progression or stable disease 1 year after initiating nivolumab therapy
Active peptic ulcer disease
Patients with extrahepatic disease, portal hypertension, or bilobar disease are allowed
Diffuse subependymal or cerebrospinal fluid (CSF) disease
Bilateral ocular adnexal involvement is permitted, if biopsy confirms unilateral disease and there is high clinical suspicion for bilateral disease, biopsy of the contralateral ocular adnexa can be waived
Must not have a rapidly progressive disease
Disease must be ER+ and HER2-
Performance status < 3, unless directly related to disease process as determined by the principal investigator
Patient must have injectable disease (direct injection or ultrasound guided)
Patients with tumors of low malignant potential, except ovarian pseudomyxoma or with no peritoneal disease
Patient must not have clinical evidence of disease progression prior to the CD8+ memory T-cell infusion
Evidence of ischemic heart disease as determined by study cardiologist
Leptomeningeal disease
FLT3-ITD or FLT3-D835 positive disease at any time during disease course.
Subject’s current disease state must be one for which there is no known curative therapy
Radiographic or cytologic evidence of leptomeningeal disease
No evidence of progressive disease on lenalidomide
A measurable residual disease at the time of screening defined as at least MRD-positive disease:\r\n* A method of evaluation of MRD is multi-parameter flow cytometry (MFC) performed at the University of Chicago\r\n* Patients who have negative MRD by multi-parameter flow cytometry (MFC) but have residual original monoclonal protein by serum or urine immunofixation may be eligible if they are found to have MRD-positive disease by next generation sequencing (NGS)
Evidence of progressive disease on lenalidomide maintenance as per IMWG criteria
Visceral crisis or rapidly progressive disease for which chemotherapy would be indicated
Patients with disease of any major organ system that would compromise their ability to withstand therapy; any significant organ impairment should be discussed with the study chair prior to patient entry
Progression of disease must be documented prior to study entry
Cutaneous T-cell lymphomas (mycosis fungoides, Sezary syndrome)\r\n* >= stage III\r\n* Disease progression >= 2 prior regimens, including at least one systemic therapy
Patients with lymphoma must ideally have at least stable disease from last therapy, however if the PI or LAI believes there is a high likelihood of response to induction chemotherapy (etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride-fludarabine phosphate+/-rituximab [EPOCH-F+/-R]), then the patient may be enrolled on the induction phase arm; for enrollment on the research phase arm, the patient must have at least stable disease which is defined as:\r\n* Absence of disease progression for at least 8 weeks after previous therapy or 12 weeks after autologous transplantation\r\n* Patients who are less than 8 weeks from previous therapy or 12 weeks from autologous transplantation may participate in the study at the discretion of the PI or LAI as long as they do not have progressive disease
Clinical T4 disease
Current histologically transformed disease.
Progressive disease
Evidence of marrow disease by flow and morphology after upfront or salvage cytoreductive therapy and before stem cell mobilization
Patients may not have impending organ compromise from disease as assessed by their treating physician
Patients must have non-measurable disease (such as nuclear medicine bone scans) and non-target lesions (such as PSA level) assessed within 28 days prior to initial administration of drug
Progressive disease or sites of new metastasis after definitive therapy for oligometastatic disease
Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration
Leptomeningeal disease
Inclusion Criteria:\n\n        Patients with a diagnosis of intermediate or high risk CLL (or variant immunophenotype),\n        SLL, or B-PLL by IWCLL 2008 criteria (48) who have:\n\n          -  Previously received at least one therapy for their disease.\n\n          -  Previously untreated disease and 65 years old OR under 65 years old and or refuse or\n             are ineligible for chemoimmunotherapy\n\n        All patients must satisfy one of the following criteria for active disease requiring\n        therapy:\n\n          -  Evidence of marrow failure as manifested by the development or worsening of anemia or\n             thrombocytopenia\n\n          -  Massive (? 6 cm below the costal margin), progressive or symptomatic splenomegaly\n\n          -  Massive nodes (? 10 cm) or progressive or symptomatic lymphadenopathy\n\n          -  Constitutional symptoms, which include any of the following:\n\n               -  Unintentional weight loss of 10% or more within 6 months\n\n               -  Significant fatigue limiting activity\n\n               -  Fevers ?100.5 degrees F for 2 weeks or more without evidence of infection\n\n               -  Night sweats >1 month without evidence of infection\n\n          -  Patients with a history of Richter's transformation are eligible if they now have\n             evidence of CLL only, with <10% large cells in the bone marrow.\n\n          -  ECOG performance status ? 2\n\n          -  Life expectancy of < 2 years or that would confound assessment of toxicity in this\n             study\n\n          -  Must be ? 18 years of age\n\n        Exclusion Criteria:\n\n          -  Any life-threatening illness, medical condition, or organ dysfunction which, in the\n             investigator's opinion, could compromise the subjects' safety, interfere with the\n             absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.\n\n          -  Subjects with active cardiovascular disease not medically controlled or those who have\n             had myocardial infarction in the past 6 months, or corrected QT interval (QTc) ?480\n             ms.\n\n          -  Malabsorption syndrome, disease significantly affecting GI function, or resection of\n             the stomach or small bowel or gastric bypass, ulcerative colitis, symptomatic\n             inflammatory bowel disease, or partial or complete bowel obstruction.\n\n          -  Grade ?2 toxicity (other than alopecia) continuing from prior anticancer therapy\n             including radiation.\n\n          -  History of a bleeding diathesis (eg, hemophilia, Von Willebrand disease).\n\n          -  Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia\n             purpura.\n\n          -  History of stroke or intracranial hemorrhage within 6 months before the first dose of\n             study drug.\n\n          -  Requires or receiving anticoagulation with warfarin or equivalent vitamin K\n             antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.\n\n          -  Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole,\n             lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).\n\n          -  Subjects with history of or ongoing drug-induced pneumonitis.\n\n          -  Subjects with human immunodeficiency virus (HIV) or active infection with hepatitis C\n             virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection.\n\n          -  Subjects who are known to have hepatitis B infection or who are hepatitis B core\n             antibody or surface antigen positive.
Disease free of other malignancies beside the ALL at the time of the study
Patients with circumferential epidural disease
Patients with paraspinal extension of disease with visceral involvement, exclusive of patients with cauda equina and sacral disease extension
Extensive disease, disease location, and/or co-morbid condition that the PI or designee considers unsafe for surgical intervention of NK cell infusion
Performance status =< 3, unless directly related to disease process as determined by the principal investigator
Lung disease resulting in dyspnea at rest.
Cardiac disease (history of and/or active disease) that would preclude the use of any of the drugs included in the treatment regimen. This includes but is not confined to:
Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow up.
Recurrent or refractory disease according to NCI criteria
Radiographic evidence of progression/recurrence of the measurable disease more than 12 weeks after the end of the initial radiation therapy
Presence of T4b disease, precluding organ preservation
T1N0 disease
Diagnosis of Gilbert’s disease
Paget’s disease of the nipple
Recurrent/progressive disease at any time
Refractory disease (i.e. less than a partial response to frontline therapy)
Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow)
Pathologic T1 or T2 disease, resected with negative margins (>= 2mm)
Pathologic N2a, N2b, or N2c disease
Presence of T3 or T4 disease
ARM 2 - BPDCN: Research participants with a diagnosis of BPDCN, according to World Health Organization (WHO) classification by hematopathology, who underwent at least 1 line of systemic therapy for BPDCN and who have persistent or recurrent disease in at least one of the following are eligible: peripheral blood, bone marrow, lymph nodes, spleen, cutaneous lesions or other sites OR participant who are at high risk for disease recurrence
Measureable disease
Patients must have previously received prior first line standard therapy (or effective salvage chemotherapy regimens) for their disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
COHORT A: Patients must have progressive disease, defined as the presence of new or growing lesion(s) on radiologic imaging within 14 months of study enrollment and/or new/worsening disease related symptoms within 14 months of study enrollment; (progression according to RECIST v 1.1 criteria is not required)
Research participants with confirmed 1st or higher relapse of disease by morphology, cytogenetics or molecular, or research participants with refractory or residual disease
First episode of progressive disease during aggressive multi-drug frontline therapy.
Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
Active CNS disease as identified by positive CSF cytospin at time of enrollment
Willingness to forego additional therapy until evidence of disease progression
Patients must have previously received prior first line standard therapy (or effective salvage chemotherapy regimens) for their disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
> 5 sites of visceral disease in lung or liver (nonspecific lung nodules =< 1 cm in diameter are permitted)
Patients with evidence of disease progression post SCT at the time of consideration for the study enrollment will not be included
Presence of leptomeningeal disease
Significant extrahepatic disease representing an imminent life-threatening outcome
Patients must have histo-pathologically confirmed diagnosis of hematologic malignancy (leukemia or lymphoma); patients to be considered will either have resistant/refractory hematologic malignancies (disease exceeding 5% by morphology or with measurable extramedullary diseases: e.g. nodal disease or chloroma) or have relapsed following an initial allogeneic HSCT; alternatively, they will have a hematologic malignancy where allogeneic HSCT is indicated and their disease is in a state of remission, but they lack a well matched donor: related, unrelated donor (URD) or umbilical cord blood (UCB) HSC source (less than 7 of 8 URD match, less than 4 of 6 UCB match and/or less than 2 x10^5 CD 34+ HSC/kg in a matched UCB product); patients between 19 and 24 years of age will have been previously diagnosed and cared for by a Pediatric Oncologist
The patient must have documented disease limited to the peritoneal surface, amenable to complete cytoreduction indicated by:\r\n* Disease confined to the peritoneal surfaces\r\n* No parenchymal liver metastases\r\n* No evidence of clinical, biochemical or radiological biliary obstruction\r\n* Small volume of disease in the gastro-hepatic ligament defined by a < 5 cm mass in the epigastric region on cross-sectional imaging\r\n* No clinical or radiological evidence of hematogenous or distant nodal metastasis
The patients have documented disease beyond the peritoneal surfaces, which prevent achieving complete cytoreduction as indicated by:\r\n* Evidence of distant hematogenous metastatic disease or distant nodal metastases\r\n* Evidence of parenchymal hepatic metastases\r\n* Evidence of clinical, biochemical or radiological biliary obstruction\r\n* Evidence of gross disease of the small bowel mesentery characterized by distortion, thickening or loss of mesenteric vascular clarity which limits ability to obtain complete cytoreduction
Isolated extra-medullary disease relapse
Measurable or assessable disease according to the “Revised Response Criteria for Malignant Lymphoma” (Cheson et al., J. Clin. Onc., 1999)105; patients in complete remission with no evidence of disease are not eligible
There is no limit as to the number or type of prior drug treatments but patients must have radiographic evidence of progressive disease
Patients with prior therapy that included interstitial brachytherapy, or Gliadel wafers must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, MR spectroscopy or surgical documentation of disease
Multi-focal disease
The extrathoracic disease must be controlled
Patients with macroscopic recurrent disease are allowed; macroscopic disease is defined as clinically detectable or evident on radiographic imaging
Any pancreatic adenocarcinoma that does not meet criteria for borderline resectable disease
Unilateral or bilateral disease meeting study criteria
Patients must have measurable disease other than the injection site or biopsy site, i.e. greater than 1.5 cm bi-dimensionally on standard computed tomography imaging
Patients must have previously received first line standard therapy (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
Histologically documented uterine leiomyosarcoma with no visible residual disease
Disease progression during or after treatment with gemcitabine (alone or in combination with other agents; at regular, not radiosensitizing, doses)
Direct bilirubin < 1.6 (unless related to Gilbert’s disease or medications)
Prior auto-immune disease
Active GI ulcer disease within 4 weeks of study enrollment
Infratentorial disease
Bi-dimensionally measurable disease (as per Revised Assessment in Neuro-Oncology [RANO] criteria)
Presence of diffuse leptomeningeal disease
Imaging or cytologic evidence of leptomeningeal disease
Relapsed/refractory MCL: Patient has relapsed and or refractory MCL and must have received at least one prior treatment regimen for their disease; patient with leukemia phase (peripheral blood involvement), leptomeningeal disease, cerebral spinal fluid (CSF) MCL, central nervous system (CNS) MCL, non-measurable disease, gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible
RECIPIENT: Patients are to be referred in remission for evaluation; should a patient have progressive disease, or a donor becomes not available after enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment; if this course of action is not in the best interest of the patient according to the clinical judgment of the principal investigator (PI)/lead associate investigator (LAI), then the patient may receive standard treatment for the malignant disease under the current study; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol
Patients with disease of any major organ system that would compromise their ability to withstand therapy
Predominance of disease that is amenable to radiotherapy
Paget’s disease of the nipple
Paget’s disease of bone
Diagnosis of secondary Haemophagocytic Lymphohistiocytosis consequent to a proven rheumatic or neoplastic disease.
Evidence of other significant disease including hematologic, renal or liver disease that is not explained by the patient’s current medical condition or concomitant disease, (i.e. levels of absolute neutrophil count [ANC], hemoglobin, platelets, clotting time, serum creatinine, etc); lab values, as determined by hematology and clinical chemistry tests, will be unacceptable if greater than +/- 2x of “normal” reference range as defined by the local hospital clinical laboratory; final decision on inclusion will be made by physician, concerning suitability of patient for surgery
Patients must have histopathologic confirmation of epidermal neutrophilic pustular skin disease
Known or suspected Gilbert's disease at the time of randomization.
Multicentric or bilateral disease unless biopsy of the clinical abnormalities are performed and result is negative.
Paget's disease of the nipple.
Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 28 days after transplant
Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
Patient must consent to a biopsy of a site of disease unless the only site of disease is lung/pleura, bone, or deemed unsafe by the principal investigator
Patient must have evaluable disease
Patients must be deemed to have borderline resectable disease (adapted from National Comprehensive Cancer Network [NCCN] Practice Guidelines in Oncology - v.2.2010) with no radiologic evidence of distant metastatic disease prior to registration; specifically, patients must have at least one designation of borderline resectable and no designation of unresectable disease
Patients who are currently undergoing or who previously underwent matched allogeneic HCT for:\r\n* AML: Prospective enrollment will now be limited to patients with relapsed disease (overt relapse or minimal residual disease) at any time post allogeneic HCT\r\n* MDS will no longer be a criterion for eligibility\r\n* CML will no longer be a criterion for eligibility
Patients who have evidence of disease progression before day 100 after ASCT
Patients will be excluded if there is radiographic or cerebrospinal fluid (CSF) cytological evidence of leptomeningeal disease
Patients with multifocal disease or leptomeningeal disease who require whole brain radiotherapy (WBRT)
Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism
Patient must not have a diagnosis of Gilbert’s disease
Persistent or recurrent elevations in levels of EBVDNA exceeding 500 copies/ml in patients previously treated for EBV lymphoproliferative disease (EBVLPD) with chemotherapy and/or Rituxan who do not yet have clinically or radiologically evaluable disease but are at high risk of disease recurrence
For subjects with HIV-associated entered after a tolerable dose has been determined, KS lesions must be either:\r\n* Increasing despite HAART and HIV suppression below the limit of detection (48 copies/mL) in the two months prior to screening or\r\n* Stable despite HAART for at least three months; stable disease must be symptomatic (examples of symptomatic disease include disease associated with pain, edema, psychological distress and/or social withdrawal)
Life-threatening visceral disease or other severe concurrent disease
Symptomatic systemic vascular disease is defined as cardiovascular disease which prevents any procedure in MRI where ECG cannot be obtained (i.e. coronary disease). These patients must be excluded
Patients must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered no evidence of disease [NED]); this includes recurrent glioblastoma multiforme (GBM) after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy
Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, MR spectroscopy or surgical/pathological documentation of disease
Patient has any disease that will obscure toxicity or dangerously alter drug metabolism
History of CD19+ malignancy with evidence of relapse or persistent minimal residual disease (MRD) following autologous or allogeneic hematopoietic stem cell transplantation (cohort 1)\r\n* Relapse on this protocol is detection of CD19+ malignancies in bone marrow (>= 5%) or extramedullary lesion by morphology, cytogenetics, molecular, radiographic, and/or flow cytometry\r\n* Persistent minimal residual disease after transplantation must be demonstrated by morphology, karyotype, fluorescent in situ hybridization (FISH), flow cytometry, or reverse transcriptase (RT)-polymerase chain reaction (PCR)
Rapidly progressive disease that in the estimation of the treating physician would compromise ability to complete study therapy
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator
Subjects must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two planes\r\n* This disease must be located primarily in the supratentorial region\r\n* Patients with significant disease that is metastatic outside of the supratentorial region are ineligible
Presence of leptomeningeal disease
Measurable disease for dose expansion and lead in phases only; measurable disease defined by:\r\n* Revised International Working Group (Cheson, 2007) classification for systemic lymphoma or \r\n* Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in blood\r\n* Or bone marrow modified severity weighted assessment tool (mSWAT) > 0 or Sezary count >= 1000 cells/uL
Solitary bone or extramedullary plasmacytoma disease only
Evidence of limited extrahepatic disease on preoperative radiological studies is acceptable if the life threatening component of disease is in the liver. Limited extrahepatic disease is defined in this protocol as follows: metastasis in bone, subcutaneous, lung or lymph nodes that is amenable to resection or radiation and has a defined treatment plan. Patients with extra-hepatic tumor burden which does not have a defined treatment plan (i.e. monitor or is unable to be resected or radiated) must not be included in the trial.
Part 2: Subjects with HNSCC, NSCLC, pancreatic ductal adenocarcinoma, salivary gland cancer, and transitional cell carcinoma of the genitourinary tract that have had disease progression after available therapies for advanced or metastatic disease that are known to confer clinical benefit, have been intolerant to treatment, or have refused standard treatment.
For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy.
Absence of residual or disseminated disease as defined by the following criteria:\r\n* Minimal residual disease as determined by post-operative imaging preferably performed within 48 hours of resection (and at most 28 days post-surgery), i.e. gross total resection or residual disease of < 1.5 cm^2 on post-operative imaging
ELIGIBILITY CRITERIA FOR REGISTRATION: subjects undergoing primary debulking surgery must have stage III or IV disease and have undergone surgery to include, at a minimum, removal of the uterus, ovaries and fallopian tubes; these patients may be optimally debulked (less than 1 cm residual disease) but must have grossly visible macroscopic residual disease OR be suboptimally debulked
Progressive disease at transplant work-up
Patients with any disease that would obscure toxicity or dangerously alter drug metabolism
Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied; patients treated on this protocol will be without morphological evidence of disease, or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemo-responsive
Histologically documented uterine carcinosarcoma with no visible residual disease
Patients can have extra-hepatic disease, provided the hepatic disease is the highest burden, the extra-hepatic disease is low burden and potentially treatable with surgery, ablative radiation therapy, or United States (US) Food and Drug Administration–approved first- or second-line systemic therapy regimens
Participants must be otherwise indicated for radiation therapy independent of this study:\r\n* For low-grade gliomas, typical indications would include at least one of:\r\n** Progressive or recurrent disease as defined by imaging\r\n** Persistence or progression of neurological symptoms (e.g., seizures), or\r\n** At risk of early progression as defined by either (a) age >= 40, (b) mindbomb homolog 1 (MIB-1) >= 3%, or (c) size > 6 cm and/or of limited resectability\r\n* For favorable grade III gliomas, typical indications would be at upfront diagnosis following maximal safe surgery or a recurrence of a lower grade tumor with metaplastic evolution to grade III disease
Subjects with recurrent disease
Evidence of disease progression defined by progressive VS growth during the previous 12 months (> 20% increase in volume, as clinically determined) in all patients; usually patients with disease progression proceed to microsurgical resection, however for those patients who are at increased risk for surgical complications (e.g., deafness, lower cranial nerve injury, facial weakness) or who refuse surgery, enrollment in the study may be the best clinical option
Paget's disease of the nipple
Philadelphia chromosome negative myeloproliferative disease
Poor-risk CLL or SLL as follows: 11q deletion disease that has progressed after a combination chemotherapy regimen, 17p deletion disease, or histologic conversion; patients with transformed lymphomas must have stable disease or better
Relapsed disease
Significant extrahepatic disease representing an imminent life-threatening outcome
Patients with malignancy are to be referred in remission for evaluation, except in the case of viral associated malignancies; should a patient have progressive disease or a donor becomes unavailable after enrollment, the patient will be referred back to their primary hematologist-oncologist for treatment; if this course of action is not in the best interest of the patient according to the clinical judgment of the principal investigator (PI)/lead associate investigator (LAI), then the patient may receive standard treatment for the malignant disease under the current study; if under either of these settings, it becomes apparent that the patient will not be able to proceed to transplant, then he/she must come off study; recipient-subjects receiving a standard therapy will be told about the therapy, associated risks, benefits alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol
=< 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant (e.g. AML chloroma obstructing the biliary tree); patients with higher bilirubin levels due to causes other than active liver disease are also eligible with principal investigator (PI) approval e.g. patients with paroxysmal nocturnal hemoglobinuria (PNH), Gilbert's disease or other hemolytic disorders
For tumors other than DSRCT, patients must have a history of tumor progression or recurrence or failure to achieve complete response with standard therapy or < 20% chance of long term disease-free survival
During phase II: all patients with relapsed disease will be eligible if they have received a minimum of 1 prior standard therapy and a maximum of 2 prior treatments (one of which must be a purine analog and/or an alkylating agent) for B-CLL and have developed relapse disease\r\n* Note: patients who have refractory disease (defined as – progressive disease on last treatment, or less than 6 months of clinical response to the last treatment) will not be eligible
Patients with Paget’s disease of the nipple
Primarily refractory or relapsed disease
Clinical stages T3-4 disease
If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease to proceed
Patients must not have any evidence of progressive disease at the time of study entry
If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease
Prior radiotherapy to the paranasal sinus region or the upper neck (i.e., prior radiotherapy to another disease site is acceptable).
Disease progression or relapse prior to HPC infusion
Significant extrahepatic disease representing an imminent life-threatening outcome
Significant extrahepatic disease representing an imminent life threatening outcome
Eligible diagnoses: patients with sickle cell anemia such as sickle cell anemia (hemoglobin [Hb] SS), Hb S/ beta° thalassemia, Hb S/beta positive (+) thalassemia, Hb SC disease, Hb SE disease, Hb SD disease, Hemoglobin SO-Arab disease Hb S/hereditary persistence of fetal hemoglobin; other significant hemoglobinopathies that also fulfills a criterion from below
Any patient with active connective tissue disease such as lupus, dermatomyositis
Persistent or rising minimal residual disease (MRD) after standard chemotherapy regimens: patients with evidence of minimal residual disease at the completion of therapy or evidence of rising MRD while on therapy; MRD will be defined by either flow cytometry (> 0.1% residual cells in the blast gate with immune phenotype of original leukemic clone), by molecular techniques (polymerase chain reaction [PCR] or fluorescent in situ hybridization [FISH]) or conventional cytogenetics (g-banding)\r\n* New leukemia subtypes: if new high risk features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee
Patients with rapidly advancing systemic disease, especially those without good options of systemic treatment for their disease outside the CNS (Cohort D)
Many patients present with concomitant systemic disease outside of the central nervous system; extra-central nervous system (CNS) disease status should meet the following criteria:\r\n* Patients with concomitant systemic disease under control with current or prior systemic treatment, as per primary treating physician\r\n* Patients without any evidence of systemic disease, either receiving systemic treatment or on active observation (Cohort D)
Chemotherapy refractory large cell and high grade NHL (i.e. progressive disease after > 2 salvage regimens)
Patients with positive resection margin or minimal residual disease (< 0.5 cm) are also eligible
Patients must have MIBG-avid NB and evaluable disease on MIBG scan at time of enrollment on protocol
All stages (I-IV) of disease
Inclusion Criteria (main):\n\n          -  Patients with advanced and/or metastatic cancer who have no available standard therapy\n             or who are not candidates for available standard therapy, and for whom, in the opinion\n             of the investigator, experimental therapy with GEN1029 may be beneficial.\n\n          -  Patient must be ? 18 years of age\n\n          -  Patients must have measurable disease according to Response Evaluation Criteria In\n             Solid Tumors (RECIST) version 1.1\n\n          -  Have an acceptable hematological status\n\n          -  Have an acceptable renal function\n\n          -  Have an acceptable liver function\n\n          -  Have an Eastern Cooperative Oncology Group performance status of 0 or 1\n\n          -  Body weight ? 40kg\n\n          -  Patients both females and males, of childbearing or reproductive potential must agree\n             to use adequate contraception from screening visit until six months after last\n             infusion of GEN1029\n\n        Exclusion Criteria (main):\n\n          -  Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for\n             at least 8 weeks prior to first GEN1029 administration\n\n          -  Have clinically significant cardiac disease\n\n          -  Uncontrolled hypertension defined as systolic blood pressure ?160 mmHg and/or\n             diastolic blood pressure ?100 mmHg, despite optimal medical management\n\n          -  Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new\n             (younger than 6 months) or progressive brain metastases or stroke\n\n          -  History of organ allograft (except for corneal transplant) or autologous or allogeneic\n             bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of\n             Investigational Medicinal Product (IMP)\n\n          -  Have received a cumulative dose of corticosteroid ? 150 mg prednisone (or equivalent\n             doses of corticosteroids) within two weeks before the first GEN1029 administration\n\n          -  History of ? grade 3 allergic reactions to monoclonal antibody therapy as well as\n             known or suspected allergy or intolerance to any agent given in the course of this\n             trial\n\n          -  Radiotherapy within 14 days prior to first GEN1029 administration\n\n          -  Any prior therapy with a compound targeting DR4 or DR5\n\n          -  History of chronic liver disease or evidence of hepatic cirrhosis
Be in urgent need of therapy for lymphoma related complications (such as hyperviscosity syndrome) and those with bulky disease
Documented disease progression on or after prior systemic treatment administered for the advanced disease including CYP 17 inhibitors and/or androgen-pathway inhibitors (i.e. abiraterone and/or enzalutamide when available) and no more than one line of chemotherapy for the advanced disease, or patients who were ineligible (unfit) to receive chemotherapy. Disease progression defined as increasing serum PSA (per PCWG3), radiological progression or ? 2 new bone lesions. (Chemical castration is required unless surgically orchiectomized.)
Malignancy other than disease under study with the exception of those from which the subject has been disease-free for more than 2 years and not expected to affect the safety of the subject or the endpoints of the trial.
Have measureable disease
History or presence of clinically relevant Central Nervous System pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens)
Patients must have at least two sites of disease amenable to biopsy
Malignant disease, other than that being treated in this study
First autologous or allogeneic HCT and hematologic disease in remission on initiation of antiviral therapy for hepatitis C infection
Patients must not have experienced radiographic disease progression or clinical signs of symptoms of instability requiring urgent intervention.
Signs and symptoms of active dental disease
Evidence of other immune related disease/conditions.
Participants must have completed 3 cycles of a bortezomib-based induction regimen (as defined by current NCCN guidelines) and have no evidence of disease progression as defined by IMWG criteria.
Ongoing or active gastritis or peptic ulcer disease.
indication for anticoagulant treatment for a disease other than the index VTE episode; Related to bleeding risk:
Cardiomyopathy primarily caused by non-amyloid diseases (e.g. ischemic heart disease; valvular heart disease)
Patient has anemia due to HbS or HbC disease, alpha or beta thalassaemia
Has disease that is suitable for local treatment administered with curative intent.
Bothersome cutaneous disease
Refractory to and disease progression within 6 months from the last dose of at least 2 lines of prior therapy
Leptomeningeal disease
Recurrent disease with an:
Glioblastoma or gliosarcoma disease with leptomeningeal spread.
Serious nonmalignant disease
Neurological symptoms related to underlying disease requiring increasing doses of corticosteroids
Patients are excluded if there is radiographic or cerebrospinal fluid (CSF) evidence of leptomeningeal disease.
Patients must have documented radiological disease progression either during or after the first-line therapy.
Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension).
Key inclusion criteria:\n\n          1. Histologically or cytologically confirmed gastric adenocarcinoma, including gastric or\n             gastroesophageal-junction adenocarcinoma (Histologically confirmed adenocarcinoma of\n             the lower esophagus acceptable with radiographic or endoscopic documentation of\n             gastroesophageal-junction or proximal-stomach involvement.)\n\n          2. Measurable disease (revised RECIST) based on computed tomography, or nonmeasurable\n             disease\n\n          3. ECOG performance status 0 or 1\n\n          4. Treatment with only 1 prior regimen (as first-line therapy) that must have included a\n             fluoropyrimidine and a platinum-containing agent (Prior adjuvant or neo-adjuvant\n             chemotherapy acceptable provided 6 months elapsed between the end of this therapy and\n             the start of first-line therapy.)\n\n          5. Disease progression after the start of the 1 prior regimen based on computed\n             tomography\n\n          6. Adequate bone marrow, hepatic, and renal function\n\n          7. Ability to swallow an oral solid-dosage form of medication\n\n        Key exclusion criteria:\n\n          1. Squamous cell gastric carcinoma\n\n          2. Bone-only metastatic disease\n\n          3. History or presence of brain metastasis or leptomeningeal disease\n\n          4. Operable gastric or gastroesophageal-junction cancer\n\n          5. HER2-positive disease if the patient has not previously been treated with an anti-HER2\n             agent\n\n          6. Uncontrolled diarrhea, nausea, or vomiting\n\n          7. Known malabsorptive disorder\n\n          8. Significant medical disease other than gastric cancer\n\n          9. Presence of neuropathy > Grade 1 (NCI Common Toxicity Criteria)\n\n         10. Prior treatment (including adjuvant therapy) with a taxane or other tubulin-targeted\n             agent (indibulin, eribulin, etc.)\n\n         11. Prior radiation therapy to more than 25% of the bone marrow\n\n         12. Need to continue any regularly-taken medication that is a potent inhibitor or inducer\n             of the CYP3A pathway\n\n         13. Pregnancy or lactation
Patients must have symptomatic disease requiring therapy; indications for therapy are defined by the iwCLL2008 criteria as follows (one or more are sufficient):\r\n* Clinical manifestations (if believed by the investigator to be caused by CLL):\r\n** Unintentional weight loss > 10% within the previous 6 months\r\n** Significant fatigue\r\n** Fevers of greater than 100.5 degrees Fahrenheit (F) (38 degrees Celsius [C]) for 2 weeks without evidence of infection\r\n** Night sweats without evidence of infection\r\n* Evidence of progressive marrow failure as manifested by the development or worsening of anemia (< 11 g/dl), thrombocytopenia (< 100,000/mm^3) or neutropenia (< 1,500/mm^3)\r\n* Massive (i.e. > 6 cm below left costal margin) or progressive splenomegaly\r\n* Massive nodes/clusters (> 5 cm) or progressive symptomatic adenopathy\r\n* Progressive lymphocytosis with an increase of > 50% over 2 month period, or an anticipated doubling time of less than 6 months\r\n* NOTE: Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for protocol therapy
Patient refractory to dacarbazine defined as patient presenting a disease progression after 3 months of dacarbazine therapy.
Active peptic ulcer disease defined as unhealed or clinically active
Patients whose only nodal disease is cystic and not PET-avid
Measureable disease.
Gastrointestinal diseases including Crohn's disease or hemorrhagic coloproctitis.
Castleman's disease (multi-centric disease)
Clinical signs of brain involvement or leptomeningeal disease
Presence of autonomous adrenocortical hormone secretion despite the absence of disease detectable with imaging techniques
Any significant medical illnesses or toxicities that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the subjects’ ability to tolerate this therapy. Subjects must not have any disease that will obscure toxicity or dangerously alter drug metabolism, e.g. congestive heart failure, moderate to severe liver and renal disease, other cancers.
Known life-threatening systemic disease
Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and experienced radiologically-confirmed disease progression
Greater than 3 months from confirmed progressive disease on Study IPI-145-07
patients with CRPC must meet PCWG3 criteria for disease progression at trial entry
Current corneal epithelial disease except mild punctate keratopathy.
Patients must have histological verification of diagnosis. Patients with M+ disease (defined as evidence of neuraxis dissemination) are not eligible. Cerebrospinal fluid (CSF) cytology is not required but may be obtained if clinically indicated prior to study enrollment. If cytology is positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible
Patients with M+ disease (defined as neuraxis dissemination either by imaging or by cytology)
209 Presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
Progressive disease at study enrollment.
Inclusion Criteria:\n\n          1. Male or female patients age ? 18 years of age at the time of informed consent\n\n          2. HLA-A*0201 positive, confirmed by central laboratory\n\n          3. NY-ESO-1 and/or LAGE-1A positive tumor confirmed by the central laboratory\n\n          4. Arm 1: Patients must be refractory to or intolerant to all existing therapies known to\n             provide clinical benefit for their condition.\n\n          5. Arm 2: Subjects will have received the following previous therapies:\n\n               1. NSCLC — PD-1/PD-L1 inhibitor\n\n               2. Patients with NSCLC and an EGFR or ALK genomic tumor aberration must have disease\n                  progression after treatment with Health Authority-approved agents for these\n                  aberrations\n\n               3. Urothelial cancer — PD-1/PD-L1 inhibitor\n\n               4. Synovial sarcoma — at least one prior chemotherapy regimen\n\n          6. Arm 1 only: Histologically confirmed diagnosis of advanced NSCLC, melanoma, urothelial\n             carcinoma, or synovial sarcoma\n\n          7. Arm 2 only: Histologically confirmed diagnosis of advanced NSCLC, urothelial\n             carcinoma, or synovial sarcoma\n\n          8. Arm 2 only: Disease amenable to biopsy\n\n          9. Arm 2 only: Measurable disease to RECIST v.1.1 criteria\n\n        Exclusion Criteria:\n\n        Impaired baseline organ function as evaluated by out-of-range laboratory values 2. History\n        of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or\n        monoclonal antibodies 3. Clinically significant cardiac disease or impaired cardiac\n        function 4. Presence of symptomatic or untreated central nervous system (CNS) metastases 5.\n        Active infection requiring systemic antibiotic therapy 6. Known history of human\n        immunodeficiency virus infection (HIV) 7. Active hepatitis B virus (HBV) or hepatitis C\n        virus (HCV) infection 8. Malignant disease, other than that being treated in this study 9.\n        Patients receiving systemic steroid therapy or any other systemic immunosuppressive\n        medication. Local steroid therapies are acceptable 10. Systemic anti-cancer therapy within\n        2 weeks of the first dose of study drug.\n\n        11. Major surgery within 2 weeks of the first dose of study drug 12. Radiotherapy within 2\n        weeks of the first dose of study drug, with the exception of palliative radiotherapy to a\n        limited field 13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF,\n        GM-CSF, M-CSF) ? 2 weeks prior to start of study drug 14. Pregnant, likely to become\n        pregnant, or lactating women
Patients who have leptomeningeal disease
Prior radiation performed to areas of measurable disease ? four weeks of study entry unless there is documented evidence of disease progression.
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded
HPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded
Patients with bladder CIS, or completely resected high grade Ta/T1 lesions that are BCG unresponsive; unresponsive is BCG refractory and/or BCG relapsing\r\n* BCG refractory: persistent high-grade disease at 6 months despite receiving at least 5-6 induction instillations and at least one maintenance (two of three instillations) in a 6 month period\r\n* BCG relapsing: recurrence of high-grade disease after achieving a disease-free state at 6 months after receiving at least 5-6 induction instillations and at least one maintenance (two of three instillations) in a 6 month period
Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
Current corneal disease except for mild punctuate keratopathy.
Current corneal disease except for mild punctuate keratopathy.
Has had documented disease progression on or within 60 days after completion of the last therapy.
Must have documentation of no evidence of disease progression of the tumor during or after completion of first line systemic anti-cancer therapy
Previously treated ALL including philadelphia chromosome (BCR-Ab1) positive ALL who meet all of the following criteria: \r\n* Diagnosis of CD19-positive B-cell ALL based on the flow cytometry and histology \r\n* Previously treated subjects with primary refractory disease OR after first or subsequent relapse \r\n* Subjects with detectable lymphoblasts in bone marrow (BM) or extramedullary disease (EMD) that is radiographically measurable and amenable to repeat biopsies
Patients must have at least ONE of the following: 1) Recurrent/progressive disease at any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease
Patients with disease of any major organ system that would compromise their ability to withstand therapy.
Biopsy confirmed multifocal, multicentric, or contralateral disease that is invasive or non-invasive
Infectious disease testing will be done per Hemacare policy and AAAB guidelines
Patients must have at least ONE of the following: 1) Recurrent/progressive disease at any time (biopsy not required, even if partial response to intervening therapy); 2) Refractory disease (i.e., less than a partial response to frontline therapy, including a minimum of 4 cycles of chemotherapy) (no biopsy is required for eligibility for this study); 3) Persistent disease after at least a partial response to frontline therapy (i.e., patient has had at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow) (patients in this category are REQUIRED to have a biopsy [bone marrow biopsy included] of at least one residual site demonstrating viable neuroblastoma)
Patients with disease of any major organ system that would compromise their ability to withstand therapy
Patients with leptomeningeal disease
Presence of adverse pathologic features at the time of prostatectomy (positive surgical margin, pathologic\r\nT?stage 3?4 disease, pathologic Gleason score 8?10 disease, presence of tertiary Gleason grade 5 disease) OR documentation of rising prostate?specific antigen on at least two consecutive draws, with the magnitude of\r\nprostate?specific antigen exceeding 0.03 ng/mL
Patients with any of the following indications for chemotherapy:\r\n* Evidence of progressive marrow failure as manifested by the development of or worsening anemia (? 11 g/dL) and/or thrombocytopenia (? 100 x 10^9/L) not due to autoimmune disease\r\n* Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly\r\n* One or more of the following disease-related symptoms:\r\n** Weight loss ? 10% within the previous 6 months\r\n** Extreme fatigue attributed to CLL\r\n** Fevers ? 100.4 degree Fahrenheit (F) for 2 weeks without evidence of infection\r\n** Drenching night sweats without evidence of infection
Patients with rectal disease
Patients with convincing evidence of extraprostatic extension or T4 disease on digital rectal examination (DRE)
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not; (NOTE: prior ibrutinib treatment is allowed as per: patients with prior exposure to ibrutinib will be allowed if they do not have disease refractory to ibrutinib; patient receiving ibrutinib will be allowed on this trial if they have measurable disease and did not have disease progression while receiving ibrutinib; prior bortezomib treatment is allowed as per: patients with prior exposure to bortezomib will be allowed if they do not have disease refractory to bortezomib)
Evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid replacement)
Has known gliomatous meningitis, extracranial disease, or multifocal disease.
For study cohort B, must have had previous treatment with cetuximab or panitumumab with disease control (defined as complete response, partial response, or stable disease) lasting for ? 4 months in duration
Disease that is amenable to serial biopsies
Life-threatening visceral disease or other severe concurrent disease
Relapsed/refractory disease
Measurable disease per modified Severity Weighted Assessment and/or Sezary count
Donors regardless of match and selection criteria must:\r\n* Not be affected by the same disease making the patient eligible for alloHCT; disease carriers may be permitted depending on the clinical situation\r\n* Meet donor criteria as outlined in University of Minnesota protocol MT2012-14C: Procedure Guidelines for Related Hematopoietic Stem Cell Donors
Patients must have adequate labs within 7 days of treatment unless cytopenia is thought to be due to underlying disease
Presence of evaluable disease according to the 2014 Lugano classification.
Disease course appropriate for therapy initiation approximately 8-12 weeks from enrollment per treating physician.
Patients will be ineligible if they have disease outside of the abdominal cavity which is uncontrolled or PET avid
Evidence of ischemic heart disease as determined by study cardiologist
The presence of diffuse leptomeningeal disease will be an exclusion criterion for this study; this is secondary to the inadequacy of measuring the extent of the tumor burden within this setting and the very poor prognosis of these patients
Acute or chronic pancreatic disease
Clinical or radiographic evidence of disease progression
No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration
Patients with disease that is suitable for local therapy administered with curative intent
For stratum B, patients must have disseminated recurrent disease (defined as multifocal disease, positive spine MRI including leptomeningeal disease and/or positive cytology within 21 days prior to study registration) and have adequate cerebrospinal fluid (CSF) flow based on spine MRI with no evidence of bulky disease or if bulky disease is present based on a CSF flow study per institutional guidelines; children must have undergone what is considered the standard of care as upfront therapy including either surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy
Patients with evidence of extraneural disease
Radiological documentation of disease progression:
Well-differentiated NET group: Disease progression while on/or after the last treatment, and this progression must have been observed within 6 months prior to start of study treatment (i.e. maximum of 24 weeks from documentation of progression until study entry). Disease must show evidence of radiological disease progression based on scans performed not more than 12 months apart.
Poorly-differentiated GEP-NEC group: Disease progression while on or after prior treatment.
At least one of the following:\r\n* Two or more high risk features OR\r\n** Gleason score 8-10\r\n** PSA >= 20 ng/mL within two months prior to registration\r\n** Clinical stage >= T3 disease, as determined by standard digital rectal examination (DRE)\r\n** Radiographic stage >= T3 disease as determined by a >= 75% probability of extracapsular extension or seminal vesicle invasion per reading radiologist\r\n* Any Gleason 9 or 10 disease OR\r\n* > 4 cores of Gleason 8 disease
Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.
Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if involved field is considered radiotherapy (RT) curative
Symptomatic or untreated leptomeningeal disease.
Malignant disease, other than that being treated in this study.
Clinical, radiographic or pathologic evidence of multicentric disease
Must have disease free status as determined by imaging within 4 weeks of dosing
Patients with CNS disease or other sites of extra-pulmonary metastases at the time of most recent episode of disease recurrence preceding enrollment
For the phase II portion of the study, subjects must have disease that is evaluable for response; subjects who have had radiation to all sites of disease are not eligible unless there is imaging evidence of active tumor, ie: increased blood volume
The subject must have stable disease after treatment of radiation with concurrent chemotherapy or in case of progression that the disease is controlled with another treatment type
Patients must have disease refractory to standard therapy or recurrent malignancy; patient’s current disease state must be one for which no known curative therapy is available; to be eligible for phase I study patients should have primary refractory or relapsed disease as evidenced by either:\r\n* Local or/and metastatic tumor recurrence or primary refractory tumor measurable on CT or magnetic resonance imaging (MRI) scans\r\n* Refractory persistent bone marrow disease with evidence of NB involvement of bone marrow in at least one site of biopsy\r\n* NB with metaiodobenzylguanidine (MIBG)-positive skeletal lesions (at least one site)\r\n* For sarcoma patients with resected pulmonary lesions pre-surgery CT scans demonstrating disease are required
ARM A: Predominant intrahepatic burden (> 75%) of disease (i.e. patients with widespread extrahepatic disease to organs other than the liver will not be included)
Patients with evaluable disease will be eligible
For subjects with glioma, specific inclusion criteria are as follows:\r\n* The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment\r\n* There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI)\r\n* For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease < 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:\r\n** New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line)\r\n** If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. i.e., > 70% tumor cell nuclei in areas), high or progressive increase in MIB-1 proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor);\r\n** Note: Given the difficulty of differentiating true progression from pseudoprogression, clinical decline alone, in the absence of radiographic or histologic confirmation of progression, will not be sufficient for definition of progressive disease in the first 12 weeks after completion of concurrent chemoradiotherapy\r\n* For patients with WHO grade III or IV glioma and progressive disease >= 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:\r\n** New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids\r\n** Increase by >= 25% in the sum of the products of perpendicular diameters between the first post-radiotherapy scan, or a subsequent scan with smaller tumor size, and the scan at 12 weeks or later on stable or increasing doses of corticosteroids\r\n** For patients receiving antiangiogenic therapy, significant increase in T2/fluid attenuated inversion recovery (FLAIR) non-enhancing lesion may also be considered progressive disease; the increased T2/FLAIR must have occurred with the patient on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy and not be a result of comorbid events (e.g., effects of radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects)\r\n** Note: Clinical deterioration alone is not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment but not for entry onto a clinical trial for recurrence\r\n* For patients with WHO grade II glioma progression is defined by any one of the following:\r\n** Development of new lesions or increase of enhancement (radiological evidence of malignant transformation)\r\n** A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not attributable to radiation effect or to comorbid events
All subjects must have documented disease progression during or after their last antimyeloma therapy
Progression of disease on the most recent restaging scan or clinically significant disease at the time of evaluation justifying enrolment in a trial in the opinion of the treating physician
Has infratentorial, or leptomeningeal evidence of recurrent disease
Documented disease refractory to at least one PD1/PD-L1 inhibitor, defined as disease progression following at least 2 infusions of the same drug; radiographic disease progression will be documented by the institutional radiologist based on any radiographic evidence (magnetic resonance imaging [MRI], computed tomography [CT], positron emission tomography [PET], or other modalities, etc.) of disease progression on two separate radiographic scans assessment obtained at least 4 weeks apart; this minimum 4-week interval is required to define PD-1 inhibitor resistance based on imaging; alternatively, clinical disease progression may be documented on examination by the treating investigator
Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
Leptomeningeal disease
Have at least one site of disease that is considered potentially suitable for treatment with SBRT
History within 3 months prior to treatment of grade 3-4 gastrointestinal (GI) bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolus, or other uncontrolled thromboembolic event
Scan within 14 days prior to initiation of study vaccinations shows no evidence of progressive disease prior to study vaccination initiation based on the Response Assessment in Neuro-Oncology (RANO) criteria; participant with progressive disease after radiation therapy will not be a candidate for the vaccine despite being previously enrolled and will be removed from the study and replaced
For gynecologic cancer cohort only recurrent or progressive disease within 30 days of the last dose of weekly paclitaxel or nab-paclitaxel
Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: \r\n * Renal insufficiency as defined by an estimated glomerular filtration rate (GFR) < 60 mL/minute\r\n * Cardiac dysfunction as defined by symptomatic coronary artery disease, congestive heart failure, valvular heart disease, cardiomyopathy, uncontrolled arrhythmia(s), or left ventricular ejection fraction < 50%\r\n * Pulmonary dysfunction that poses a risk of mortality after transplant, defined as pulmonary disease-moderate, using pre-transplant pulmonary function testing per the Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Manual\r\n * Necroinflammatory or fibrotic liver disease with evidence of liver dysfunction, including but not limited to jaundice, hepatic encephalopathy, or portal hypertension\r\n * Marrow dysfunction that poses a risk of peri-transplant mortality, defined as an absolute neutrophil count or lymphocyte count below the lower limit of normal, or a platelet count below 50,000/mm^3\r\n * Poorly controlled hypertension despite appropriate therapy, defined as a diastolic blood pressure greater than 90 mm Hg while on therapy\r\n * Neurologic dysfunction that affects activities of daily living and medical care\r\n * Poorly controlled diabetes mellitus, defined as persistent hyperglycemia despite therapy or recurrent hypoglycemia while on therapy\r\n * Extreme protein-calorie malnutrition defined by body mass index < 18 kg/m^2 and unintentional weight loss (3 kg in the last month or 6 kg in the last 6 months)
Patients must have at least ONE of the following:\r\n* Recurrent/progressive disease at any time prior to enrollment - regardless of response to frontline therapy\r\n* Refractory disease: persistent sites of disease (after less than a partial response to frontline therapy, following a minimum of 4 cycles of induction therapy) AND patient has never had a relapse/progression\r\n* Persistent disease: persistent disease after achieving at least a partial response to frontline therapy after a minimum of 4 cycles of induction therapy and patient has never had a relapse/progression
Patients with histologically or cytologically proven lung or esophageal cancers, thymic or mediastinal germ cell tumors, malignant pleural mesotheliomas, or primary thoracic sarcomas, as well as patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura that have no clinical evidence of active disease (NED) or minimal residual disease (MRD) not readily accessible by non-invasive biopsy or resection/radiation following standard therapy
Patients with thyroid disease should be excluded unless euthyroid on suppressive or replacement therapy
High-risk medulloblastoma defined by any of the following:\r\n* > 1.5 cm^2 residual disease for any medulloblastoma histology, or\r\n* Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery unless contraindicated, or\r\n* Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or\r\n* M4 disease
Active disease per International Workshop on Chronic Lymphocytic (IWCLL) 2008 criteria, as defined as one of the following:\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia\r\n* Massive (i.e., at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly\r\n* Massive nodes (i.e., at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy\r\n* Progressive lymphocytosis with an increase of more than 50 percent over a two-month period or lymphocyte doubling time (LDT) of less than six months; LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of two weeks over an observation period of two to three months; in patients with initial blood lymphocyte counts of less than 30 x 10^9/L (30,000/L), LDT should not be used as a single parameter to define a treatment indication; in addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infection) should be excluded\r\n* Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy\r\n* Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: \r\n** Unintentional weight loss of 10 percent or more within the previous six months\r\n** Significant fatigue (i.e., ECOG performance scale [PS] 2 or worse; inability to work or perform usual activities) \r\n** Fevers higher than 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for two or more weeks without other evidence of infection\r\n** Night sweats for more than one month without evidence of infection
Extrahepatic disease
Patients with measureable or non-measureable disease are eligible
Life-threatening visceral disease or other severe concurrent disease
Patients must have histologic or cytologic verification of extra-ocular retinoblastoma; extra-ocular disease includes orbital disease, optic nerve involvement at the surgical margin, regional nodal disease, and/or overt distant metastatic disease (at sites such as bone, bone marrow, liver and/or the central nervous system); patients with trilateral retinoblastoma will also be included in this protocol\r\n* Patients with a CNS lesion consistent with trilateral or stage 4b disease may be enrolled without tissue confirmation if (1) unequivocal leptomeningeal disease is present on brain or spine magnetic resonance imaging (MRI) scan and/or (2) the primary tumor is at least 2 cm in diameter, predominantly solid, and demonstrates enhancement on the post-gadolinium images; however, even in such cases surgery should be given serious consideration
If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by infectious disease
Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy; stable disease is acceptable to move forward provided it is non-bulky
Patients judged not to be candidates for radical cystectomy; patients with pN+ or T4b disease are considered to have unresectable disease
Known leptomeningeal disease or CNS midline shifts
Documented disease progression at study entry
Available for long-term follow-up of their disease after treatment
Patients with nasopharyngeal, paranasal sinus, skin, or unknown primary site disease
Progressive or recurrent breast cancer defined as disease progression or recurrence while on a combination of exemestane with everolimus
Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations; tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site; limited neck dissections retrieving =< 4 nodes are permitted and considered as non-therapeutic nodal excisions
Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease; in other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed
Disease status: stable disease or better at the time of enrollment
Progressive disease at the time of enrollment
Primary disease site involving the oropharynx
Intrinsic lung disease resulting in dyspnea
Lactate dehydrogenase (LDH) < 5 × upper limits of normal\r\n* (NOTE: these criteria will select against patients with bulky disease and will select for patients with less disease and earlier disease)
The following will not be exclusionary:\r\n* Resolved ipilimumab associated inflammatory disease\r\n* The presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody [ANA] titer) without associated symptoms\r\n* Subjects with vitiligo, thyroiditis, or atopic dermatitis, but otherwise not meeting this criterion may be enrolled; individual cases can be discussed with the sponsor
Patients must have received at least one prior regimen of chemotherapy for symptomatic multiple myeloma; patients may not have more than six (6) previous regimens of therapy for the disease; prior chemotherapy must have been completed at least 21 days prior to registration; for study purposes, a regimen is defined as follows:\r\n* An anti-myeloma therapy used at the time of initial diagnosis or documented disease progression which is given with the intent to decrease disease burden\r\n* Any maintenance therapy used after an Induction should be considered part of that Induction regimen\r\n* Use of any agent or combination of agents more than once during the patient’s disease history for separate documented disease progressions will be counted as separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial diagnosis and achieves response, but then progresses and receives lenalidomide/bortezomib after progression, these count as 2 separate regimens)\r\n* In cases of allogeneic or autologous stem cell transplant, the entire induction + stem cell mobilization + conditioning + planned maintenance should be considered one regimen
With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
Hypomethylating agent (azacitidine and/or decitabine) failure, defined as lack of response, disease progression, loss of response, or intolerance as deemed by the study investigator
Indirect hyperbilirubinemia due to Gilbert’s disease or hemolysis is permitted
All disease should be deemed resectable based on imaging studies e.g.:\r\n* Hepatic metastases (unilateral or bilateral =< 5 lesions, =< 15 cm total diameter)\r\n** Note: Hepatic lesions must be amenable to complete resection\r\n* Primary peritoneal metastases (small disease load =< P2 disease) without massive ascites or intestinal obstruction\r\n* Lung metastases (=< 3 unilateral/bilateral, 9 cm total diameter)\r\n** Note: lung lesions must be amenable to complete resection\r\n** Note: Patients with both pulmonary and hepatic metastases will be enrolled at the discretion of the principal investigator (PI)\r\n** Note: In situations where resection to completeness of cytoreduction score (CC) 0 or 1 is uncertain, patients may undergo diagnostic laparoscopy prior to enrollment to determine feasibility of resection
No rapidly progressive disease
Biopsy proven WM with relapsed/refractory symptomatic disease are eligible for\n             enrollment.
Symptomatic disease, as defined by the IWWM, includes the following criteria:\n             Hemoglobin less than 10 g/dL, platelet count less than 100,000 uL, bulky adenopathy\n             or organomegaly, symptomatic hyperviscosity syndrome, severe neuropathy, amyloidosis,\n             cryoglobulinemia, cold agglutinin disease, or evidence of transformation high-grade\n             non-Hodgkin's lymphoma.
Castration resistant prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression despite castrated level of testosterone (< 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy; disease progression has to be demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:\r\n* PSA: two consecutive rising PSA values, at least 7 days apart\r\n* Measurable disease: >= 20% increase in the sum of the longest diameters of all measurable lesions or the development of any new lesions; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response\r\n* Non-measurable disease: \r\n** Soft tissue disease: the appearance of 1 or more lesions, and/or equivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n** Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression
History of any of the following, unless approval is given by the Protocol Chair:\r\n* Heart disease, including acute myocardial infarction\r\n* Cardiac arrhythmias, including sick sinus syndrome\r\n* Pulmonary disease with a known forced expiratory volume (FEV) of < 1.5 or on oxygen\r\n* Gastrointestinal disease, surgery or malabsorption that could potentially impact the absorption of the study drug\r\n* Patients requiring the use of a feeding tube\r\n* Inability to swallow tablets
Patient with group classification A disease, or group classification B stage I or II disease with normal lactate dehydrogenase (LDH) level AND tumor mass less than 7 cm; NOTE: Patients who would be excluded from treatment on this protocol strictly for laboratory or performance status abnormalities can be included at the principal investigator’s discretion after consultation with the members of the Texas Children's Hospital (TXCH) Lymphoma Team
Patients must have evaluable disease
Scleroderma or active connective tissue disease
Unresectable disease
Due to the possible effect of treatment with ipilimumab on the immunologic response to infectious disease vaccines, patients must not have had any infectious disease vaccination (e.g, standard influenza, H1N1 influenza, pneumococcal, meningococcal, tetanus toxoid) within 4 weeks prior to randomization
At screening, patients may be included if the largest lesion is > 1 cm or > 3 in number, and there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy
Patients with para-aortic nodal disease or who require extended field radiotherapy beyond the pelvis
PHASE II: Patients must have extensive stage, histologically or cytologically confirmed small cell lung cancer; NOTE: the extensive disease classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive disease patients are defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy
Patient must have a CD19-expressing B cell acute lymphoblastic leukemia (ALL) or lymphoma and must have relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen; in view of the principal investigator (PI) and the primary oncologist, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time
Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis
Recurrent or refractory ALL limited to isolated testicular disease
Hyperleukocytosis (>= 50,000 blasts/uL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
Bulky disease by CT, defined as any single mass > 10 cm in its greatest diameter
Patients must have progressive disease
Patients who at the discretion of the investigator are deemed to have rapidly progressive disease
Existing non-malignant disease that would preclude the administration of pasireotide
Gall bladder disease or bile duct disease
Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism or cardiac failure
Patients must have had progressive disease after at least one line of endocrine therapy for metastatic disease (includes relapse while receiving endocrine therapy); there should be at least 1 week interval between the last endocrine treatment for an aromatase inhibitor and at least 2 weeks for tamoxifen or fulvestrant
Patients with documented evidence of leptomeningeal disease
Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)
All stages of disease
Histologic diagnosis of resected stages IIIC/ IV melanoma, with no evidence of disease clinically and radiologically; all melanomas regardless of primary site of disease will be allowed
Patients with any high-risk features will also be eligible, including those who:\r\n* Fail to achieve complete remission with initial combination chemotherapy\r\n* Patients with bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass >= 5 cm or other residual mass >= 10 cm accompanied by other features of persisting disease (e.g., Gallium or positron emission tomography (PET) scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible; if possible, persistent disease should be proven by biopsy
Have, at entry, confirmed by a pathology report: Carcinoma in situ (CIS) only; Ta/T1 high-grade disease with concomitant CIS; or Ta/T1 high-grade disease without concomitant CIS
Exception: those who have T1 high-grade disease at first evaluation after induction BCG alone (at least 5 of 6 doses) may qualify in the absence of disease progression
Known brain/leptomengial involvement of the disease, active neurological disease, dementia
Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
Has evaluable disease as defined as lesions that can be accurately measured at least in one dimension by radiographic examination or physical examination and other lesions such as bone lesions, leptomeningeal disease, ascites, hepatosplenomegaly from disease.
Target Disease Exceptions
Disease Related Criteria:
Patients must have clinically evident recurrent disease for the purpose of this study
Patients whom have already undergone secondary cytoreduction for recurrent disease are excluded
Brain metastases or active leptomeningeal disease (with the exception of participants with treated epidural disease and no other epidural progression)
Evaluable disease;
Patients must have achieved stable disease, a partial response, or a complete response at their first disease assessment after initiating first-line platinum-based chemotherapy; patients determined to have progressed (in the opinion of the treating physician) at their first disease assessment are not eligible
Part B: Diagnosis of MM with relapsed or refractory disease with previous exposure to PI (e.g., bortezomib or carfilzomib), IMiDs (e.g., lenalidomide or pomalidomide), and daratumumab, and refractory (based on IMWG criteria) to their last line of therapy
CIS (with or without papillary disease) OR
Any grade T1 papillary disease OR
The subject's disease is refractory or has relapsed following adequate BCG treatment. Refractory disease is defined as disease which persists at the first evaluation following adequate BCG. Relapsed disease is defined as having a complete response to adequate BCG but recurs at a subsequent evaluation. Subjects will enroll into one of three cohorts based on their type of disease and the time to refractory/relapsed disease following their last dose of BCG as follows:
Cohort 1: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment.
Disease progression despite Androgen Deprivation Therapy
Patients must have completed 3 cycles of R-CHOP with no evidence of disease progression
Registration within 42 days of evidence of disease progression
Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed.
For patients with Grade IV GBM, recurrent disease at the time of the first or second recurrence or progression. For patients with Grade III anaplastic gliomas, recurrent disease at the time of at least a first recurrence but no more than a fourth recurrence or progression
Radiographically measureable disease.
All patients must have at least ONE site of evaluable disease.
Patients with disease of any major organ system that would compromise their ability to withstand therapy.
Disease progression after 1 prior ALK inhibitor therapy other than crizotinib. Patients may have had any number of prior chemotherapy regimens in any disease setting.
Inclusion Criteria for dose escalation and expansion phase:\n\n          -  Signed written informed consent\n\n          -  Male or female subjects aged greater than or equal to 18 years\n\n          -  Subjects must have histologically or cytologically proven metastatic or locally\n             advanced solid tumors, for which no standard therapy exists or standard therapy has\n             failed. Availability of tumor archival material or fresh biopsies is optional for\n             subjects in dose escalation\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry\n             and an estimated life expectancy of at least 3 months\n\n          -  Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST\n             1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or\n             metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease\n             without a measureable lesion\n\n          -  Adequate hematological, hepatic and renal function as defined in the protocol\n\n          -  Effective contraception for both male and female subjects if the risk of conception\n             exists\n\n          -  Other protocol defined inclusion criteria could apply\n\n        Inclusion Criteria for expansion phase:\n\n          -  Subjects must have relapsed, refractory, or progressive disease following last line of\n             treatment (with the exception of the gastric and gastroesophageal junction (GEJ)\n             cancer cohort, which does not require progression). Availability of tumor archival\n             material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in\n             the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen\n             must have been collected within 90 days prior to the first investigational medicinal\n             product (IMP) administration. Specifically, the following will be required:\n\n          -  NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or\n             stage IV NSCLC that has progressed after 1 line of platinum-containing doublet\n             chemotherapy. Subjects should have received only 1 line of platinum-containing\n             treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing\n             regimen is not sufficient for eligibility because not received in the context of a\n             metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA\n\n          -  NSCLC first line: Stage IV (per 7th International Association for the Study of Lung\n             Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven.\n             Subjects must not have received treatment for their metastatic or recurrent disease.\n             No activating epidermal growth factor receptor (EGFR) mutation nor ALK\n             translocation/re-arrangement\n\n          -  Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or\n             metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with\n             first-line chemotherapy combination with or without disease progression. Subjects\n             should have received no more than 1 line of treatment for metastatic disease. Subjects\n             should not have been treated with trastuzumab (but can be Human Epidermal growth\n             factor Receptor 2 [HER2] positive). Subjects who received any platinum containing\n             doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately\n             candidates for surgery will also be eligible, as long as they did not have progressive\n             disease after completion of the neoadjuvant chemotherapy. In addition, subjects with\n             gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte\n             count is as defined in the protocol\n\n          -  MBC: Subjects must have histologically confirmed locally advanced or MBC and have\n             tumor that is refractory to or progressive after standard of care therapy. Subjects\n             must have received no more than 3 prior lines of cytotoxic therapy for metastatic\n             disease. Subjects must have received a taxane and an anthracycline, unless\n             contra-indicated\n\n          -  Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic\n             castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC,\n             mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol\n\n          -  Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer\n             (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as\n             defined in the protocol\n\n               -  Other protocol defined inclusion criteria for expansion phase could apply\n\n        Exclusion Criteria for dose escalation and expansion phase:\n\n          -  Concurrent treatment with a non-permitted drug\n\n          -  Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins\n             (immune checkpoints)\n\n          -  Concurrent anticancer treatment, major surgery, or use of any investigational drug\n             within 28 days before the start of trial treatment; or concurrent systemic therapy\n             with immunosuppressive agents, use of hormonal agents within 7 days before the start\n             of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate\n             or denosumab are eligible provided treatment was initiated at least 14 days before the\n             first dose of avelumab.\n\n          -  Previous malignant disease other than the target malignancy to be investigated in this\n             trial within the last 5 years with the exception of basal or squamous cell carcinoma\n             of the skin or cervical carcinoma in situ\n\n          -  Rapidly progressive disease (for example, tumor lysis syndrome)\n\n          -  Active or history of central nervous system metastases\n\n          -  Receipt of any organ transplantation including allogeneic stem-cell transplantation\n\n          -  Significant acute or chronic infections as defined in the protocol\n\n          -  Active or history of any autoimmune disease (subjects with diabetes Type 1, vitiligo,\n             psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are\n             eligible) or immunodeficiencies\n\n          -  Known severe hypersensitivity reactions to monoclonal antibodies, any history of\n             anaphylaxis, or uncontrolled asthma\n\n          -  Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0,\n             however sensory neuropathy less than or equal to Grade 2 is acceptable\n\n          -  Pregnancy or lactation period\n\n          -  Known alcohol or drug abuse\n\n          -  Clinically significant (that is, active) cardiovascular disease\n\n          -  All other significant diseases (for example, inflammatory bowel disease), which, in\n             the opinion of the investigator, might impair the subject's tolerance of trial\n             treatment\n\n          -  Any psychiatric condition that would prohibit the understanding or rendering of\n             informed consent\n\n          -  Legal incapacity or limited legal capacity\n\n          -  Non-oncology vaccine therapies for prevention of infection disease (for example,\n             seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug\n             administration. Vaccination while on study is also prohibited except for\n             administration of the inactivated influenza vaccine
Disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
Has disease that is suitable for local therapy administered with curative intent.
Progression of systemic disease at Screening
Leptomeningeal disease
Patients at initial presentation of melanoma must undergo an adequate wide excision of the primary lesion, if present; patients with previously diagnosed melanoma must have had all current disease resected with pathologically negative margins and must have no evidence of disease at the primary site or must undergo re-resection of the primary site; a full lymphadenectomy meeting the criteria outlined is required for all node-positive patients including those with positive sentinel nodes; patients with recurrent disease who have had a prior complete lymphadenectomy fulfill this requirement as long as all recurrent disease has been resected; for all patients, all disease must have been resected with negative pathological margins and no clinical, radiologic, or pathological evidence of any incompletely resected melanoma; patients must be registered within 98 days of the last surgery performed to render the patient free of disease
Isolated extra-medullary disease relapse
Leptomeningeal disease.
The subject has disease that is not amenable to a curative treatment approach.
Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer [AJCC] 7th edition T1-4N0-1M1)
Patients presenting with tumors within the kidneys (multiple synchronous or single/multiple metachronous) are not eligible if there are no extrarenal sites of disease (i.e. potential multifocal primary disease)
Patient must have no active peptic ulcer disease
Patients who have an option for any treatment with proven clinical benefit for CD25-positive AML or CD25-positive ALL at current state of disease.
CNS disease prophylaxis must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
Patient has recurrence or progression of disease during or after AI therapy (i.e. letrozole, anastrozole, exemestane).
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
Subject has a history of peripheral artery disease (eg, claudication, Leo Buerger's disease).
Leptomeningeal disease
Malignancies other than disease under study within 5 years
AML with antecedent hematological disease (e.g., myelodysplastic syndrome (MDS), myelofibrosis, polycythemia vera, etc.) and not a candidate for stem cell transplantation (SCT) in their current disease state.
AML with antecedent hematological disease (e.g., myelodysplastic syndrome (MDS), myelofibrosis, polycythemia vera, etc.) and not a candidate for SCT in their current disease state.
Disease must be considered incurable; incurable is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection)
Phase II only: \r\n* Arm 1: disease progression after at least one cycle of prior treatment with cisplatin or carboplatin for incurable disease; prior treatment with cetuximab for incurable disease is not permitted\r\n* Arms 2 and 3: disease progression after at least one cycle of treatment with cetuximab for incurable disease
Patient must be planning to undergo complete cytoreduction of all peritoneal disease
Has high risk bone metastases that are asymptomatic or minimally symptomatic (not requiring opioids). High risks metastases are defined as: 1. bulkiest sites of osseous disease >= 2 cm, 2. disease involving the hip (acetabulum, femoral head, femoral neck), shoulder (acromion, glenoid, humeral head), or sacroiliac joints 3. disease in long bones with 1/3-2/3 cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpus, phalanges) 4. disease in junctional spine (C7-T1, T12-L1, L5-S1) and/or disease with posterior element involvement
Leptomeningeal disease
Proliferative disease (WBC > 30 x 109 /L) (confirmed at time of study entry prior to first dose)
Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
Subject must not have primary refractory disease
Has measureable disease
Residual invasive disease post-neoadjuvant either in the breast or as residual nodal invasion.
Progressive disease during or after last treatment regimen.
REGISTRATION #2 - PRIOR TO CONSOLIDATION CHEMOTHERAPY: Patients must have undergone restaging tests according to the study calendar and determined to have no evidence of disease progression
There must be residual disease
Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency ablation must show evidence of subsequent progressive disease (substantial size increase of ? 20%) to be deemed a target lesion.
Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible
Requires urgent palliative intervention for primary disease.
Any immunodeficiency disease or immune-compromised state
Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
T-ALL or T-LBL participants with relapsed/refractory disease.
Isolated extra-medullary disease relapse
Malignancies other than disease under study within 5 years prior to D1 of C1
Disease evaluable for response by specific appropriate criteria.
No or minimal disease-related symptoms not affecting patient daily activities.
Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease.
Transformed disease is permitted
Leptomeningeal disease
Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
Must have achieved at least a stable disease (SD) for at least 1 cycle of treatment to at least 1 prior anti-myeloma regimen before developing Progressive disease (PD) (relapsed)
Disease is suitable for local therapy administered with curative intent
Patients with immediately life-threatening visceral disease, for whom chemotherapy is the preferred treatment option.
Progressive disease on androgen deprivation therapy at enrollment;
Radiographically measureable disease
Radiographically measureable disease
Received first-line combination therapy containing oxaliplatin and fluoropyrimidine with or without bevacizumab for metastatic disease with documented evidence of disease progression during or after treatment completion
Radiographically measureable disease
Specific eligibility criteria for Part 2 CRPC expansion cohort: Persistent disease with evidence of disease progression following standard therapy(ies) including prior treatment with androgen/androgen receptor directed therapy, including enzalutamide and/or abiraterone
Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1
All disease stages
Patients must not have clinical evidence of leptomeningeal disease (a spinal tap does not need to be performed)
Clinically relevant central nervous system pathology requiring treatment such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
Evaluable disease
Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease greater than 1.5cm diameter
Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
Measureable (target) disease.
Has a disease that is suitable for therapy administered with curative intent.
Patients must be at least 3 weeks from prior thoracotomy (if performed); if prior thoracotomy then measurable disease on imaging must be present
Experienced progression/recurrence of disease during or subsequent to the most recent anti-cancer regimen.
Patients who have any option for other treatment for B-cell NHL at the current state of disease.
Subject must not have primary refractory disease
Measurable disease as defined per RECIST v. 1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measureable if disease progression at the treated site after completion of therapy is clearly documented.
Documented progressive disease according to RECIST v1.1 (Appendix 2) following receipt of at least 2 cycles of one platinum-containing chemotherapy regimen administered for R/M disease (min. 50 mg/m2 for cisplatin, minimum area under the curve [AUC] > 4 for carboplatin).
Progressive disease within 3 months after completion of curatively intended treatment for locoregionally advanced SCCHN.
Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 0-2 prior lines of systemic therapy
Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 0-3 prior lines of systemic therapy
Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment
Patients who only present with localized disease
relapsed and/or refractory disease
Weekly paclitaxel for recurrent or persistent disease.
Inclusion Criteria:\n\n        Cohort A:\n\n          1. Subjects with newly diagnosed, untreated, unmethylated MGMT GBM who are eligible for\n             standard radiation therapy.\n\n             Cohorts B, B2, B3 and C:\n\n          2. First or second recurrence of GBM by diagnostic biopsy or contrast enhanced MRI per\n             modified RANO criteria (122), with last baseline MRI confirmation within 14 days prior\n             to Study Day 1.\n\n             NOTE: Recurrence is defined as progression following therapy (i.e., chemotherapy;\n             radiation). If the subject had a surgical resection for relapsed disease and no\n             anti-tumor therapy was administered for up to 12 weeks, and the subject has further\n             evidence of tumor growth or undergoes another resection, this will be considered as\n             one episode of recurrence.\n\n          3. On Study Day 1, at least 12 weeks from prior radiotherapy (unless progressive disease\n             outside of the radiation field or histopathologic confirmation of unequivocal tumor).\n\n          4. Cohort B, B2, B3: No prior VEGF/VEGFR targeted therapy; Cohort C: No more than one\n             prior bevacizumab regimen.\n\n          5. Recovery from any prior treatment clinically significant, related adverse events to\n             grade ? 1 or pretreatment baseline with the exception of alopecia and laboratory\n             values listed per inclusion criteria.\n\n             Cohorts A, B, B2, B3 and C:\n\n          6. Subjects with measurable or non-measurable disease.\n\n          7. Histopathologic confirmation of glioblastoma.\n\n          8. At the time of Study Day 1, subjects must be at least 4 weeks since major surgical\n             procedure, open biopsy, or significant traumatic injury; there should be no\n             anticipation of need for major surgical procedure during the course of the study.\n\n             There should be no core biopsy or other minor surgical procedure, excluding placement\n             of a vascular access device, within 7 days prior to Study Day 1.\n\n          9. Subjects who have previously been treated with the Optune device are eligible for the\n             study as long as toxicity related to the treatment has resolved to ? Grade 1 or\n             baseline.\n\n         10. ECOG ? 1 or Karnofsky performance status of ? 70.\n\n         11. Adequate hematologic, renal and hepatic function, as defined below:\n\n               -  Absolute Neutrophil Count ? 1000/mm3\n\n               -  Platelet count ? 100,000/mm3\n\n               -  Total bilirubin ? 1.5 x ULN; or if subject has Gilbert syndrome, then total\n                  bilirubin ? 3 x ULN\n\n               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? 2.0 x ULN\n\n               -  Creatinine ? 1.5x ULN or creatinine clearance (CrCl) ? 50 mL/min (using the\n                  Cockcroft-Gault formula):\n\n                    -  Female CrCl = (140 - age in years) x weight in kg x 0.85 /72 x serum\n                       creatinine in mg/dL\n\n                    -  Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine\n                       in mg/dL Cohorts B2, B3 and C\n\n               -  Urinary protein quantitative value of ? 30 mg/dL in urinalysis or ?1+ on\n                  dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample.\n\n         12. Age must be greater than or equal to 18 years at date of consent.\n\n         13. Written informed consent and any locally required authorization (e.g., Health\n             Insurance Portability and Accountability Act [HIPAA] in the USA) obtained from the\n             subject/legal representative prior to performing any protocol-related procedures,\n             including screening evaluations.\n\n        Exclusion Criteria:\n\n        All Cohorts\n\n          1. Primary tumors localized to the brainstem or spinal cord.\n\n          2. Locally directed therapies including but not limited to stereotactic radiosurgery,\n             re-irradiation, Gliadel, and therapeutics administered by direct injection or\n             convection-enhanced delivery within 6 months of start of study treatment.\n\n          3. Prior exposure to MEDI4736 or other anti-PD-1, anti-PD-L1, anti-CTLA4 antibodies.\n\n          4. Presence of diffuse leptomeningeal disease or extracranial disease.\n\n          5. Active, suspected or prior documented autoimmune disease (including inflammatory bowel\n             disease, celiac disease, irritable bowel syndrome, Wegner's granulomatosis and\n             Hashimoto's thyroiditis). Subjects with vitiligo, type I diabetes mellitus, residual\n             hypothyroidism due to autoimmune condition only requiring hormone replacement,\n             psoriasis not requiring systemic treatment, or conditions not expected to recur in the\n             absence of an external trigger are permitted to enroll.\n\n          6. Known primary immunodeficiency or active HIV.\n\n          7. Known active or chronic viral hepatitis or history of any type of hepatitis within the\n             last 6 months indicated by positive test for hepatitis B surface antigen (HBV sAG) or\n             hepatitis C virus ribonucleic acid (HCV antibody).\n\n          8. History of organ transplant requiring use of immunosuppressive medication.\n\n          9. History of active tuberculosis.\n\n         10. Significant active systemic illness including infections requiring intravenous\n             antibiotics.\n\n         11. Current pneumonitis or interstitial lung disease.\n\n         12. Other invasive malignancy within 2 years prior to entry into the study, except for\n             those treated with surgical therapy only.\n\n         13. History of severe allergic reactions to any unknown allergens or any components of the\n             study drugs.\n\n         14. Any prior Grade ? 3 immune-related adverse event (irAE) or any prior\n             corticosteroid-refractory irAE.\n\n         15. Mental impairment that may compromise the ability to give informed consent and comply\n             with the requirements of the study.\n\n         16. Lack of availability for follow-up assessments.\n\n         17. Lack of availability for Post Study Follow-up contacts to determine relapse and\n             survival.\n\n         18. Women who are breast-feeding or pregnant as evidenced by positive serum pregnancy test\n             (minimum sensitivity 25 IU/L or equivalent units of HCG).\n\n         19. Women of childbearing potential not using a medically acceptable means of\n             contraception for the duration of the study and unsterilized males not willing to\n             abide by requirements for contraception as stated in Section 5.4.\n\n         20. If a subject previously received another investigational treatment, the last dose of\n             investigational treatment was administered within 4 weeks of Day 1 of the study.\n\n         21. Any condition that, in the clinical judgment of the treating physician, is likely to\n             prevent the subject from complying with any aspect of the protocol or that may put the\n             subject at unacceptable risk.\n\n         22. Cohorts B2, B3 and C:\n\n               -  Evidence of hemorrhage on the baseline MRI or CT scan other than those that are ?\n                  grade 1 and either post-operative or stable on at least two consecutive scans\n\n               -  Current use of warfarin sodium or any other Coumadin-derivative anticoagulant.\n                  Participant must be off Coumadin-derivative anticoagulants for at least seven\n                  days prior to starting study drug. Low molecular weight heparin and Factor Xa\n                  antagonists are allowed\n\n               -  History of clinically significant bleeding within 6 months of enrollment\n\n               -  History of arterial thromboembolism within 12 months prior to enrollment\n\n               -  Inadequately controlled hypertension (defined as systolic blood pressure 150\n                  and/or diastolic blood pressure > 90 mmHg on antihypertensive medications)\n\n               -  Any prior history of hypertensive crisis or hypertensive encephalopathy\n\n               -  Clinically significant cardiovascular disease within 12 months prior to\n                  enrollment (or randomization), including myocardial infarction, unstable angina,\n                  grade 2 or greater peripheral vascular disease, cerebrovascular accident,\n                  transient ischemic attack, congestive heart failure, or arrhythmias not\n                  controlled by outpatient medication, percutaneous transluminal coronary\n                  angioplasty/stent\n\n               -  Evidence of bleeding diathesis or coagulopathy\n\n               -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal\n                  abscess within 6 months prior to study enrollment\n\n               -  Serious, non healing wound, ulcer, or bone fracture
All subjects must have histologic evidence of G4 MG (including glioblastoma and gliosarcoma) and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bidimensional product of enhancement, a new enhancing lesion, or significant increase in T2 FLAIR).
Progression of bone disease according to PCWG3 criteria
Progression: patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible; patients deemed to have pseudoprogression are eligible
For all other malignancies, the subject is eligible if they have undergone potentially curative therapy and they have been considered disease free for at least 5 years prior to Screening.
Subject should have stable disease for at least 6 months on the current regimen with the last 2 scans taken at least 6 weeks apart; measurable disease is not required
Disease progression >1 year after completing adjuvant therapy for Stage I-IIIA disease and no systemic therapy for the recurrent disease
Metastatic disease, unresectable disease involving one or more sites including liver, lung, lymph nodes and peritoneum, with each nodule measuring =< 3 cm OR no more than two sites of disease (two nodules) > 4.5 cm
EXCLUSION FOR TREATMENT: Rapidly progressive disease that in the estimation of the treating physician would compromise ability to complete study therapy
Applicable disease and eligible for myeloablative SCT
Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
Subjects with Glioblastoma multiforme (GBM) do not have to have objectively measurable disease at entry.
Progression of disease after last therapy demonstrated by RANO criteria
Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease).
Continued treatment with bevacizumab with documented evidence of disease progression on a bevacizumab-containing regimen
Disease that is suitable for local therapy administered with curative intent.
Histologic diagnosis of resected stages IIIB/IIIC/IV melanoma, with no evidence of disease clinically and radiologically, and negative surgical margins; all melanomas regardless of primary site of disease will be allowed
Patients who have disease progression prior to completion of intended frontline therapy, including patients demonstrating disease progression after interval cytoreduction
Patients with known auto-immune disease
Leptomeningeal disease
Metastatic disease not amenable to surgical curative treatment and eligible to receive therapy with mFOLFOX6 (Leucovorin/5-Fluorouracil/Oxaliplatin) + bevacizumab.
Subject who has documented active relapsed or refractory disease requiring therapeutic intervention.
Subject who has active auto-immune disease.
Radiologic evidence of progressive disease (according to [RECIST Version 1.1) either during or within 6 months after stopping their most recent systemic therapy for RCC before enrollment into this study.
Presence of unstable systemic disease (e.g., visceral crisis or rapid progression) in the judgment of the investigator
Participants with MDS, CMML, or low blast AML, whose only site of disease is extramedullary, example, the skin.
Disease surgically resectable with curative intent
direct extension of neck disease to involve the external skin;
Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease. Patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excluded
Distant metastases (M1 disease).
Patients with disseminated disease to the spine are not eligible, and MRI of spine must be performed prior to enrollment if the treating physician suspects disseminated disease.
Any other malignant disease
Tumor progression during or immediately after completion of =< 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
Active auto-immune disease
Current active infectious disease
Experienced an investigator-determined confirmed cutaneous or radiographic disease progression after stopping their initial treatment with MK-3475
Relapsed or refractory disease. Relapse is defined as progression of disease after an initial response to previous treatment, more than 60 days after cessation of treatment. Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment
Histological confirmation of disease with documented disease relapse after the last therapy requiring treatment per the treating physician. Participants with lymphoma must have at least 1 measurable site of disease (Part 2 only). In addition, B-cell malignancy disease-specific criteria specified in the protocol must also be met
Active coronary artery disease.
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
Disease-free of other malignancies
Patients must have no evidence of muscle invasive disease
Patients have either Cis or Cis with Ta and/or T1 disease at enrollment or in the past. For those patients with only Ta or T1 disease at enrollment AND with no history of Cis, they must have
For relapsed disease:
Has infratentorial, or leptomeningeal evidence of recurrent disease
Definitive clinical or radiologic evidence of progressive disease
Patients who have disease progression during, or after, receiving abiraterone treatment in any setting.
Patients must have confirmed Cushing's disease that is persistent or recurrent.
Patients are permitted to washout current drug therapy to meet these entry criteria if they have a known diagnosis of Cushing's disease.
Patients must have documented disease progression while on Arm 1 of this protocol; the follow-up tumor assessment form documenting disease progression must be submitted to Southwestern Oncology Group (SWOG) prior to Step 3 Crossover Registration
Prior regorafenib use with disease progression (expanded cohort only)
Known significant or active coronary artery disease (CAD) or peripheral vascular disease (PVD) or cardiovascular disease (CVD) defined as abnormal stress test, symptoms, or requiring medication for the prevention of symptoms
ENTRY CRITERIA:\n\n        DISEASE CHARACTERISTICS:\n\n          -  Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at\n             least two different previous regimens.\n\n               -  Refractory disease is defined as progressive disease while on therapy or\n                  progression within 60 days of therapy.\n\n               -  Progressive disease is defined by a 25% increase from the lowest response value\n                  in specified tests.\n\n          -  Measurable disease as defined by at least one of the following:\n\n               -  Serum M-protein ? 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA)\n\n               -  Urine M-protein ? 200mg/24hours\n\n               -  Serum free light chains ? 10 mg/dL and abnormal kappa/lambda ratio\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No anti-myeloma treatments within 14 days before the start of study treatment.\n\n          -  Must have recovered from side effects of prior treatments.\n\n        PATIENT CHARACTERISTICS:\n\n        Performance Status\n\n        • ECOG 0, 1, or 2\n\n        Bone Marrow Reserve\n\n          -  Absolute neutrophil count (AGC/ANC) ? 1000/uL\n\n          -  Platelets ? 30,000/uL\n\n          -  Hemoglobin ? 8g/dL\n\n          -  Absolute lymphocytes ? 800/uL\n\n          -  Leukocytes ? 3,000/uL\n\n        Renal Function\n\n        • Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ? 1.5 X ULN\n\n        Hepatic Function\n\n          -  Total bilirubin ? 2.0 X ULN\n\n          -  AST, ALT, ALP ? 3.0 X ULN, or ? 5.0 X ULN (if liver metastases exist)\n\n          -  No positive Hep C serology or active Hep B infection\n\n        Cardiovascular\n\n          -  No congestive heart failure < 6 months\n\n          -  No unstable angina pectoris < 6 months\n\n          -  No myocardial infarction < 6 months\n\n          -  No history of ventricular arrhythmias\n\n          -  No history of supraventricular arrhythmias\n\n          -  No NYHA Class > II CHF\n\n          -  No marked baseline prolongation of QT/QTc interval\n\n        Pulmonary\n\n        • Normal clinical assessment of pulmonary function\n\n        Other\n\n          -  Negative serum pregnancy test if female and of childbearing potential\n\n          -  Women who are not pregnant or nursing\n\n          -  Subjects, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study\n\n          -  No known autoimmune disease other than corrected hypothyroidism\n\n          -  No known prior organ allograft or allogeneic transplantation\n\n          -  Not HIV positive\n\n          -  No history or evidence of uncontrollable CNS disease\n\n          -  No psychiatric illness/social situation\n\n          -  No other illness that in the opinion of the investigator would exclude the subject\n             from participating in the study\n\n          -  Must provide informed consent and HIPPA authorization and agree to comply with all\n             protocol-specified procedures and follow-up evaluations\n\n          -  No active systemic infection requiring parenteral antibiotic therapy\n\n          -  No on-going chronic systemic corticosteroid (>10 mg daily prednisone equivalent) use\n             or other immunosuppressive therapy (a history of mild asthma not requiring therapy is\n             eligible). Inhaled or topical steroids, and adrenal replacement steroid doses ? 10 mg\n             daily prednisone equivalent, are permitted in the absence of active autoimmune\n             disease.
Paget's disease of the nipple
Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
Documentation of keratosis follicularis (also known as Darier or Darier-White disease)
Target Disease Exceptions
Active peptic ulcer disease even if asymptomatic
Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with ibrutinib and rituximab
Need of treatment for relapsed, progressed or refractory disease as assessed by the investigator.
Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable)
Patients must have had all gross disease resected (R0 or R1 resection)
Patients with T1, N0M0 disease are not eligible
Untreated central nervous system metastases that are either symptomatic or greater than 1 cm at time of therapy; lesions that are > 1cm that have been irradiated and in the opinion of the PI or sub-I no longer represent active disease may be allowed
Patients must have at least stable disease (no overt progressive disease) at the time of study registration
Patient must not have obvious clinical progression of lymphoma after PBSCT as determined by the treating physician; NOTE: Restaging imaging studies are NOT required for eligibility if there is no clinical suspicion of progressive disease
For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound; patients must have ONE of the following:\r\n* First episode of recurrent disease following completion of aggressive multi-drug frontline therapy\r\n* First episode of progressive disease during aggressive multi-drug frontline therapy\r\n* Primary resistant/refractory disease (less than partial response by INRC) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, etc.)
Injectable disease (ie, suitable for direct injection or through the use of ultrasound [US] guidance) defined as follows:
Cerebral/meningeal disease, including signs and symptoms of progressive multifocal leukoencephalopathy (PML)
COHORT 1 ONLY (UROTHELIAL PROGRESSIVE DISEASE)
Patients must have progressive metastatic disease; progressive will be defined as new or progressive lesions on cross-sectional imaging
Patients must have progressive metastatic disease; progressive disease will be defined as new or progressive lesions on cross-sectional imaging
Surgically rendered free of disease within 90 days of randomization
The disease needs to be in one of the following stages:\r\n* At diagnosis or in first relapse AND the patient is unable to receive conventional chemotherapy for his/her condition\r\n* In second or subsequent relapse\r\n* With residual disease after autologous, syngeneic or allogeneic hematopoietic stem cell transplantation (HSCT)
Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon positron emission tomography (PET), Thallium scanning, MR spectroscopy/perfusion, progression outside of radiation field, or surgical documentation of disease; if the additional imaging is unable to be performed for insurance or other reasons, the principal investigator (PI) will review the available imaging to determine if patients is eligible
Patients with any disease that will obscure toxicity or dangerously alter drug metabolism
Acute or chronic pancreatic disease
Patients with pN+ or > T1 disease or who have not had a visibly complete TURBT
Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
Patients taking ruxolitinib at the time of enrollment must be deemed to have had a suboptimal response (less than partial response per IWG criteria) to ruxolitinib single-agent therapy or deemed to have progression of disease (per IWG criteria)
Evidence of disease transformation at the time of study entry
Criteria for Inclusion:\n\n          1. Female patient ? 18 years\n\n          2. Willing and able to give informed consent\n\n          3. Stage III-IV platinum-sensitive (defined as a lack of progression by RECIST v1.1\n             criteria following completion of standard-of-care chemotherapy, including a minimum of\n             4 cycles of a platinum-containing regimen) epithelial ovarian, fallopian tube or\n             primary peritoneal carcinoma in first remission.\n\n          4. Histologic documentation of diagnosis of carcinoma is required and the following\n             histologic subtypes are eligible: high grade (grade ?3+) serous or endometrioid\n             carcinoma, carcinosarcoma, or poorly-differentiated adenocarcinoma, or mixed\n             (including above subtypes only). Note that synchronous serous or endometrioid uterine\n             or fallopian cancers are allowed.\n\n          5. The patient must have demonstrated an objective response (PR or CR) or stable disease\n             (SD) with the last chemotherapy prior to enrollment and this response must be stable\n             (without progressive disease) before randomization.\n\n          6. Patients must receive their first dose of vaccine within 1 year of completion of their\n             final dose of a chemotherapeutic agent of the platinum-containing regimen\n\n          7. Adequate normal organ and marrow function within 14 days prior to first vaccine\n             administration:\n\n               -  Absolute neutrophil count > 1.5 x 109/L\n\n               -  Platelet > 100 x 109/L\n\n               -  Hemoglobin > 9.0 g/dL\n\n               -  Serum bilirubin < 1.5 times ULN (unless Gilbert's syndrome without concurrent\n                  clinically significant liver disease\n\n               -  AST/ALT < 2.5 ULN unless liver metastasis in which case it must be < 5 x ULN\n\n               -  Serum creatinine CL > 40 mL/min by Cockcroft-Gault formula.\n\n          8. Anti-nuclear antibody (ANA) negative or low-positive institutional range, as\n             determined within 28 days from registration. Intermediate values (usually defined by a\n             titer of ?1:80, or as indicated by institutional range) are acceptable if there are,\n             in the opinion of the Investigator, no early signs of an autoimmune disease.\n\n          9. Female subjects must either be of non-reproductive potential (i.e. post-menopause by\n             history: > 60 years old and no menses for > 12 months naturally or secondary to\n             radiation/chemotherapy; OR serum FSH, LH and estradiol levels in the post-menopausal\n             range; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history\n             of bilateral oophorectomy), or must have a negative serum pregnancy test upon study\n             entry\n\n         10. Life expectancy > 24 weeks\n\n         11. ECOG performance status of 0 or 1\n\n         12. Formalin fixed, paraffin embedded tumor sample from the primary cancer must be sent\n             for central testing.\n\n        Criteria for Exclusion\n\n          1. Histology consistent with non-serous, non-endometrioid (i.e. mucinous or clear cell),\n             or low-grade or borderline serous ovarian carcinoma\n\n          2. Patients with a history of other cancers (other than non-melanoma skin cancers [i.e.\n             basal or squamous cell]) within the past 3 years.\n\n          3. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted\n             therapy, biological/cell therapy, tumor embolization, monoclonal antibodies, other\n             investigational agent) < 28 days prior to the first dose of study drug.\n\n          4. Current or prior use of immunosuppressive medication within 28 days prior to the fist\n             dose of study drug with the exception of topical, intranasal or inhaled\n             corticosteroids or systemic corticosteroids at physiological doses, which are not to\n             exceed 10 mg/day of prednisone, or an equivalent corticosteroid.\n\n          5. Active autoimmune disease requiring therapy within the past 2 years. Note: patients\n             with vitiligo, Grave's disease or psoriasis not requiring systemic treatment within\n             the past 2 years are not excluded.\n\n          6. History of hypersensitivity to GM-CSF\n\n          7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active\n             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable\n             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active\n             bleeding diatheses including any subject known to have evidence of acute or chronic\n             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric\n             illness/social situations that would limit compliance with study requirements or\n             compromise the ability of the subject to give written informed consent\n\n          8. Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor,\n             TPO, thyroglobulin).\n\n          9. Subjects who are pregnant or are breast feeding.\n\n         10. Subjects who or of reproductive potential, and are either:\n\n               -  Not abstinent;\n\n               -  Not in an exclusive relationship with a partner who is surgically sterile;\n\n               -  Not employing an effective method of birth control.\n\n         11. Any condition that, in the opinion of the investigator, would interfere with\n             evaluation of study treatment or interpretation of patient safety or study results\n\n         12. Symptomatic or uncontrolled brain metastasis requiring concurrent treatment, inclusive\n             of but not limited to surgery, radiation and/or corticosteroids\n\n         13. Subject with uncontrolled seizures
Experienced disease progression after having received 1 prior next generation androgen receptor-targeted therapy for castration-resistant disease
Relapse or refractory disease after at least 1 systemic therapy
Non-resectable disease
The patient must have a pathologically confirmed (by histology or cytology) diagnosis of SCLC, which is currently extensive disease.
Malignant disease, other than that being treated in this study
Disease and disease status:
Fluorodeoxyglucose-avid disease (based on local evaluation) per the Lugano Classification. Fluorodeoxyglucose-avid disease is defined as disease with a 5-point scale score of 4 or 5.
Primary refractory disease
Relapsed or refractory disease after first or later salvage therapy
Inclusion Criteria:\n\n        For patients participating in any part of the trial:\n\n          -  has an advanced solid tumor previously treated with, or inability to tolerate,\n             standard therapy for the disease, or for which a standard therapy does not exist, and\n             as such is considered a candidate for Phase 1 treatment\n\n          -  has adequate organ function: Hgb ?9 g/dL; absolute neutrophil count (ANC) ? 1.5x109/L;\n             plt ? 100,000/?L; AST and ALT < 2.5x ULN (< 5x ULN in patients with liver metastases);\n             total bilirubin < 2.0 mg/dL; serum creatinine ? 1.5x ULN\n\n          -  ECOG performance score 0-2\n\n        For patients participating in any expansion group:\n\n          -  has measurable disease based on RECIST 1.1 as determined by the treating investigator.\n             Tumor lesions in a previously irradiated area are considered measurable if progression\n             has been demonstrated in such lesions\n\n          -  willing to consent for biopsy is strongly recommended but not mandatory\n\n          -  recovery of toxicities related to any prior treatments to at least Grade 1 by CTCAE v\n             4.03. Exceptions are patients with adverse event(s) that are clinically nonsignificant\n             and/or stable on supportive therapy.\n\n        For patients participating in specific expansion groups:\n\n        Cutaneous Melanoma:\n\n          -  unresectable, locally advanced or metastatic (AJCC stage IIIB, IIIC, or IV) cutaneous\n             malignant melanoma\n\n          -  relapsed or progressive disease after or unable to tolerate at least one prior\n             systemic anticancer regimen for metastatic disease involving immunotherapy (anti-PD-1,\n             anti-PD-L1, or anti-CTLA-4)\n\n          -  in tumors with a relevant BRAF mutation, relapsed, refactory, or unable to tolerate at\n             least one prior systemic anticancer regimen for metastic disease involving a BRAF\n             inhibitor\n\n        Uveal Melanoma:\n\n          -  uveal melanoma at metastic stage\n\n        Small Cell Lung Cancer:\n\n          -  extensive disease previously treated with, or inability to tolerate, platinum-based\n             chemotherapy\n\n        Exclusion Criteria:\n\n          -  has primary CNS malignancy\n\n          -  history of untreated brain mets or leptomeningeal disease or spinal cord compression\n\n          -  effects of prior anticancer therapy recovered to grade < 2\n\n          -  known HIV\n\n          -  active infection\n\n          -  major surgery within 2 weeks\n\n          -  history of another malignancy within 2 years prior
Autoimmune disease with the exception of controlled/treated hypothyroidism, disease-related immune thrombocytopenic purpura, or hemolytic anemia
SCCHN that has progressed during or following at least 1 and up to 5 prior systemic treatments for metastatic or recurrent disease deemed to be incurable. Patient who refuse radical resection for recurrent disease or are intolerant of or refused standard first line therapy are eligible to enroll
Inclusion Criteria:\n\n        Signed informed consent; Histologically confirmed gastric, esophageal, or gastro-esophageal\n        junction adenocarcinoma; disease that is locally advanced (unresectable), metastatic, or\n        locally recurrent disease; Measurable or non-measurable, but radiologically evaluable\n        disease, according to RECIST; ErbB2 (HER2)positive; Age =18 years; ECOG Performance status\n        = 2; Adequate organ function, including adequate hematologic, renal and liver function;\n        Cardiac ejection fraction within institutional range of normal as measured by\n        echocardiogram; Able to swallow and retain oral medications, and/or receive enteral\n        medications via gastrectomy feeding tube; Women and men with potential to have children\n        must be willing to practice acceptable methods of birth control during the study; Prior\n        gastric surgery is permitted if > 3 weeks prior and recovered; Prior chemotherapy for\n        non-gastric malignancy if > than 5 years; Prior neoadjuvant and/or adjuvant chemotherapy\n        for early stage gastric cancer if > 6 months since completion; At least 4 weeks since prior\n        radiotherapy; Prior biologic, hormonal, or immunologic cancer treatment if > 5 years since\n        treatment.\n\n        Exclusion Criteria:\n\n        Pregnant or lactating females; Known history of active CNS disease; Uncontrolled ascites;\n        Concurrent anti-cancer therapy; Gastric carcinoid, epidermoid, sarcomas, or squamous cell\n        carcinoma; Prior palliative chemotherapy for the treatment of gastric cancer; Prior\n        treatment with oxaliplatin < 12 months; Malabsorption syndrome or uncontrolled inflammatory\n        gastrointestinal disease; Known history of uncontrolled or symptomatic angina, arrhythmias,\n        or congestive heart failure; Pre-existing grade = 2 motor or sensory neuropathy;\n        Uncontrolled infection; Concurrent disease or condition that would make the subject\n        inappropriate for study participation or any serious medical condition that would interfere\n        with the subject''s safety; Active hepatic or biliary disease; History of other malignancy\n        except if disease-free for 5 years, a history of completely resected non-melanoma skin\n        cancer, or a successfully treated in situ carcinoma; Unresolved or unstable serious\n        toxicity from prior administration of another investigational drug and/or prior cancer\n        treatment; Dementia, altered mental status, or any psychiatric condition that would\n        prohibit the understanding or rendering of informed consent; Known history of DPD\n        deficiency; Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs\n        chemically related to lapatinib, capecitabine, fluorouracil, platins or their excipients;\n        Use of any investigational drug within 30 days prior randomization; Use of concurrent\n        prohibited medications that would interact with study medications
Inclusion Criteria:\n\n        A woman will be eligible for inclusion in this study if she meets all of the following\n        criteria:\n\n          -  Age >18 to <70 years old.\n\n          -  Has known ER and PR status\n\n          -  Has HER2 nonamplified disease, confirmed by FISH\n\n          -  Has known menopausal status (see Section 7.3 for criteria)\n\n          -  Has operable, histologically confirmed, Stage I, IIA, IIB, or IIIA, IIIB, or IIIC\n             invasive carcinoma of the breast. Bilateral synchronous breast cancer is allowable\n             provided that 1 primary meets the inclusion criteria.\n\n          -  Meets 1 of the 3 following criteria:\n\n               -  T1-3N1-3M0 if ER positive or negative\n\n               -  T2-3N0M0 if ER positive or negative\n\n               -  T1N0M0 if ER and PR negative\n\n          -  Has complete surgical resection of the primary breast tumor: either lumpectomy or\n             mastectomy with sentinel lymph node biopsy or axillary dissection, with clear margins\n             for both invasive and ductal carcinoma in situ (DCIS)\n\n          -  Has had no prior chemotherapy unless >5 years ago\n\n          -  Has an ECOG Performance Status (PS) 0-1\n\n          -  Has laboratory values of: See protocol for specific details\n\n          -  Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline\n             phosphatase (ALP) within the ranges shown below. In determining eligibility the more\n             abnormal of the 2 values (AST or ALT) should be used. See protocol for specific\n             details\n\n          -  Has normal cardiac function as evidenced by a LVEF >50%, but WNL by institutional\n             standard by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be\n             used if MUGA is not available, but the same modality must be used consistently\n             throughout the study to evaluate LVEF. Ejection fraction as determined by ECHO must be\n             WNL by institutional standard.\n\n          -  Has no evidence of metastatic disease outside of breast by physical examination and\n             chest x-ray. Other scans if done as needed by the patient (eg, bone scan; abdominal,\n             chest CT; PET or PET/CT; ultrasound; or MRI should indicate no evidence of metastatic\n             disease\n\n          -  Has had baseline bilateral mammography\n\n          -  It has been <84 days since the date of definitive surgery (eg, mastectomy or, in the\n             case of a breast-sparing procedure, axillary dissection) with adequate wound healing,\n             as determined by the Treating Physician\n\n          -  Has a negative serum pregnancy test within 7 calendar days prior to registration\n             (female patients of childbearing potential [not surgically sterilized and between\n             menarche and 1 year postmenopause])\n\n          -  If fertile, patient has agreed to use an acceptable method of birth control (barrier\n             contraceptive only) to avoid pregnancy for the duration of the study and for a period\n             of 3 months thereafter\n\n          -  Has adequate tumor specimen available for FISH analysis of TOP2A status (See Appendix\n             VI).\n\n          -  Has signed a Patient Informed Consent Form\n\n          -  Has signed a Patient Authorization Form\n\n        Exclusion Criteria:\n\n        A woman will be excluded from this study if she meets any of the following criteria:\n\n          -  Has any evidence of metastatic disease following surgical resection of the primary\n             tumor including: positive surgical margins, staging work-up, or physical examination\n             suspicious for malignant disease\n\n          -  Has T4 disease (ie, patients with fixed tumors, peau d'orange skin changes, skin\n             ulcerations, or inflammatory changes)\n\n          -  Has Stage IV breast cancer (M1 disease on TNM staging system)\n\n          -  Has a history of severe hypersensitivity reaction to drugs formulated with polysorbate\n             80\n\n          -  Has had neoadjuvant chemotherapy for this breast cancer\n\n          -  Has ever had a myocardial infarction (MI) or has a history of heart failure,\n             uncontrolled angina, severe uncontrolled arrhythmias, pericardial disease, or\n             electrocardiographic evidence of acute ischemic changes\n\n          -  Is receiving concurrent immunotherapy, hormonal therapy (eg, tamoxifen, hormone\n             replacement therapy), or radiation therapy. Must discontinue prior to registering on\n             the study.\n\n          -  Is receiving concurrent investigational therapy or has received such therapy within\n             the past 30 calendar days\n\n          -  Has peripheral neuropathy >Grade 1\n\n          -  Has had a major organ allograft or condition requiring chronic immunosuppression (ie,\n             kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases). Patients\n             who have received corneal transplants or cadaver skin or bone transplants are\n             eligible.\n\n          -  Has a serious uncontrolled intercurrent medical or psychiatric illness, including\n             serious viral (including clinically defined AIDS), bacterial or fungal infection; or\n             history of uncontrolled seizures, or diabetes, or CNS disorders deemed by the Treating\n             Physician to be clinically significant, precluding informed consent\n\n          -  Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is\n             known to be HIV positive\n\n          -  Has a history of other malignancy within the last 5 years (except cured basal cell\n             carcinoma of skin, carcinoma in situ of uterine cervix, DCIS, which could affect the\n             diagnosis or assessment of any of the study drugs\n\n          -  In an obese patient to whom the Treating Physician would not be comfortable\n             administering full doses of study drugs as calculated by the BSA. Obese patients will\n             be treated based on actual body weight. Obese patients treated with full doses based\n             on actual BSA are eligible.\n\n          -  Is pregnant or breastfeeding\n\n          -  Is deemed unable to comply with requirements of study
Subjects must have completed or had disease progression on at least one prior line of disease-appropriate therapy or not be candidates for therapy of proven efficacy for their disease
Leptomeningeal disease
Greater than 12 weeks from radiotherapy, to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as pseudoprogression of disease, unless the recurrence is a new lesion, outside the primary radiation field or the patient fulfills criteria for early progressive disease by RANO ((Wen et al., 2010); Appendix C).
Radiological evidence of multifocal disease, tumors extending into or crossing the corpus callosum or leptomeningeal disease.
Need for urgent palliative intervention for primary disease (e.g., impending herniation).
Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging per immune-related response criteria (irRC).
Participants must have been randomized to Arm A of the study and had radiographic disease progression according to RECIST 1.1
Participants must have a mandatory biopsy at the time of disease progression according to RECIST 1.1 prior to crossing over. If not clinically feasible, discussion with Sponsor is required
Patients must have advanced or recurrent disease that is refractory to curative treatment based on imaging or clinical exam.
Prior treatment with >= 4 cycles of a hypomethylating agent (decitabine or azacitidine) without response OR documented disease progression on or after hypomethylating agent therapy
Patients must have documentation of a new or progressive lesion on a radiologic imaging study performed within 6 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 6 months prior to study enrollment; note: this assessment will be performed by the treating investigator; evidence of progression by RECIST criteria is not required
Patients with Paget's disease of the bone
Immunocompromised status due to:\r\n* Human immunodeficiency virus (HIV) positivity\r\n* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease; patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed\r\n* Other immunodeficiency diseases\r\n* Splenectomy
Acute or chronic pancreatic disease
Progressive metastatic disease defined by one of the following, occurring within 6 months of study entry:\r\n* At least a 20% increase in radiologically or clinically measurable disease\r\n* Appearance of any new lesion\r\n* Symptomatic disease (including worsening hormonal symptoms or symptoms related to tumor burden)
Previous local therapy (e.g., chemoembolization or bland embolization) is allowed if completed > 6 weeks prior to study entry; for such patients, there must be either progression of measurable disease documented within the treatment field, or measurable progressive disease outside the treatment field prior to study entry
Patients with M1 disease or a history of M1 disease
Widespread progressive disease, i.e., more than three sites of progressive disease (note that more than three sites of disease are permitted provided there are no more than three sites of progressive disease)
Evidence of progressive disease within 12 months of study entry
Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 1-2 prior lines of systemic therapy
Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 1-3 prior lines of systemic therapy
HER2-positive disease
Non-CNS progression of disease as assessed by the investigator/treating physician, for which a change in systemic therapy is planned OR achievement of stable or responsive non-CNS disease for which a holiday from the current systemic therapy is planned, as assessed by the investigator/treating physician
Patient has an active concurrent malignancy/life-threatening disease. If there is a history of prior malignancies/life-threatening diseases, the patient is to be disease free for at least 5 years. Patients with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease.
For all other malignancies, the subject is eligible if he/she has undergone potentially curative therapy and has been considered disease free for at least 3 years prior to Screening.
Evidence of recurrent or progressive underlying malignant disease
Evidence of recurrent or progressive underlying malignant disease
There is no evidence of disease relapse at the time of screening, and minimal residual disease (MRD) is acceptable
Patients who have undergone resection of primary disease
Bone only disease if there are lytic lesions is also allowed and treatment response will be evaluated based on the MD Anderson criteria
Evidence of tumor progression by MRI scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan
Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum regimen; treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed
Systemic disease must be well-controlled or no evidence of disease (NED) in the opinion of the patient’s primary oncologist
Progressive systemic disease
Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
Disease progression within 60 days of discontinuation from most recent therapy
Similar condition with an expectation of > 95% five-year disease-free survival
Disease progression on or after pemetrexed and cis- or carboplatin
Serious nonmalignant disease.
Subject had disease refractory to an AI
HER-2/neu status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab
Transformed disease (assessed by investigator):
Disease suitable for local therapy administered with curative intent
Has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
Presence of biopsiable disease and willingness to undergo pre-treatment biopsy
Must have stable disease or disease response as evidenced on CT evaluation a minimum of 28 days and a maximum of 56 days following the completion of chemoradiation
Has known carcinomatous meningitis, extracranial disease, or multifocal disease
Has presence of diffuse leptomeningeal disease or extracranial disease
Measureable disease
Disease that is suitable for local therapy administered with curative intent
Relapsed refractory disease after at least 1 but not more than 4 lines of previous systemic therapy
Patients are required to have evaluable disease
Patients may not have a known history of leptomeningeal disease, as diagnosed by positive cerebrospinal fluid (CSF) cytology, unless prospective permission for enrollment is granted from the sponsor and the PI
Has rapid progression of visceral disease and, thus is a candidate for docetaxel; this determination will be at the discretion of the treating physician
Leptomeningeal disease
Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded; patient should have complete resolution of their systemic disease not requiring additional systemic therapy (e.g. maintenance rituximab or Decadron)
Previous failure of at least one fluoropyrimidine- and irinotecan-containing chemotherapy regimen for metastatic disease; Note: previous failure is defined as disease progression while receiving treatment or within 6 weeks after the last dose of irinotecan; failure for this assessment is defined as any enlargement of measurable or assessable lesion(s) or the development of any new lesion; a rising tumor marker alone is not sufficient to define failure; patients can have received irinotecan in any previous line of therapy
Diffuse subependymal or cerebral spinal fluid (CSF) disease
In the dose-expansion phase, patients must be cetuximab-resistant by fulfilling at least one of the criteria defined below:\r\n* Disease recurrence within 6 months of completing definitive radiotherapy for locally advanced disease; radiation must have included concurrent cetuximab; induction chemotherapy, if given, may or may not have included cetuximab\r\n* Disease progression during, or within 6 months, of cetuximab treatment in the recurrent/metastatic setting; prior cetuximab exposure may have occurred in first, second and/or third line\r\n* If the most recent line of therapy included cetuximab, a two-week washout period without cetuximab dosing is required
Extension of malignant disease into the anal canal
Inclusion Criteria:\n\n        Disease Related:\n\n          1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.\n\n          2. Age 65 yrs and older OR if less than 65 years, must have at least one of the following\n             criteria:\n\n               -  Cumulative Illness Rating Score (CIRS) >6\n\n               -  Creatinine clearance estimated <70 mL/min using Cockcroft-Gault equation.\n\n               -  Del 17p by FISH or TP53 mutation by PCR or Next Generation Sequencing\n\n          3. Active disease meeting at least 1 of the following IWCLL criteria for requiring\n             treatment:\n\n               -  Evidence of progressive marrow failure as manifested by the development of, or\n                  worsening of, anemia and thrombocytopenia\n\n               -  Massive, progressive, or symptomatic splenomegaly\n\n               -  Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic\n                  lymphadenopathy.\n\n               -  Progressive lymphocytosis with an increase of more than 50 percent over a 2-month\n                  period or a lymphocyte doubling time (LDT) of <6 months. LDT may be obtained by\n                  linear regression extrapolation of absolute lymphocyte counts obtained at\n                  intervals of 2 weeks over an observation period of 2 to 3 months. In patients\n                  with initial blood lymphocyte counts of <3,000/µL, LDT should not be used as a\n                  single parameter to define indication for treatment. In addition, factors\n                  contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections)\n                  should be excluded.\n\n               -  Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly\n                  responsive to corticosteroids or other standard therapy.\n\n               -  Autoimmune hemolytic anemia is defined by at least one marker of hemolysis\n                  (indirect bilirubin above the upper limit of normal (ULN) not due to liver\n                  disease, increased lactate dehydrogenase (above ULN) without alternative\n                  etiology, or increased absolute reticulocytosis (above ULN) or bone marrow\n                  erythropoiesis in the absence of bleeding AND at least one marker direct or\n                  indirect autoimmune mechanism (positive direct antiglobulin for IgG or C3d, cold\n                  agglutinins).\n\n               -  Immune thrombocytopenia is defined by platelets ?100,000/µL and increased\n                  megakaryocytes on the bone marrow exam.\n\n               -  Constitutional symptoms, defined as one or more of the following disease-related\n                  symptoms or signs, documented in the patient's record prior to randomization:\n\n               -  unintentional weight loss >10 percent within 6 months prior to screening.\n\n               -  significant fatigue (inability to work or perform usual activities).\n\n               -  fevers >100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence\n                  of infection.\n\n               -  night sweats for more than 1 month prior to screening without evidence of\n                  infection.\n\n          4. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node\n             >1.5 cm in the longest diameter in a site that has not been previously irradiated. An\n             irradiated lesion may be assessed for measurable disease only if there has been\n             documented progression in that lesion since radiotherapy has ended.\n\n             Laboratory\n\n          5. Adequate hematologic function independent of transfusion and growth factor support for\n             at least 7 days prior to screening and randomization.\n\n          6. Adequate hepatic and renal function\n\n          7. Men and women ? 18 years of age.\n\n          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n\n        Exclusion Criteria:\n\n          1. Any prior treatment of CLL or SLL\n\n          2. Evidence of central nervous system (CNS) involvement with primary disease of CLL/SLL\n\n          3. History of other malignancies, except:\n\n               -  Malignancy treated with curative intent and with no known active disease present\n                  for ?3 years before the first dose of study drug and felt to be at low risk for\n                  recurrence by treating physician.\n\n          4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura\n\n          5. Known or suspected history of Richter's transformation.\n\n          6. Concurrent administration of >20mg/day of prednisone within 7 days of randomization\n             unless indicated for prophylaxis or management of allergic reactions (eg, contrast)\n\n          7. Known hypersensitivity to one or more study drugs\n\n          8. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.\n\n          9. Any uncontrolled active systemic infection or an infection requiring systemic\n             treatment that was completed ? 7 days before randomization.\n\n         10. Known bleeding disorders or hemophilia.\n\n         11. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.\n\n         12. Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus\n             (HBV) or hepatitis C virus (HCV).\n\n         13. Major surgery within 4 weeks of randomization.\n\n         14. Any life-threatening illness, medical condition, or organ system dysfunction that, in\n             the investigator's opinion, could compromise the subject's safety or put the study\n             outcomes at undue risk.\n\n         15. Currently active, clinically significant cardiovascular disease, such as uncontrolled\n             arrhythmia or Class 3 or 4 congestive heart failure or a history of myocardial\n             infarction, unstable angina, or acute coronary syndrome within 6 months prior to\n             randomization.\n\n         16. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting\n             gastrointestinal function, or resection of the stomach or small bowel, symptomatic\n             inflammatory bowel disease or ulcerative colitis, or partial or complete bowel\n             obstruction.\n\n         17. Concomitant use of warfarin or other vitamin K antagonists.\n\n         18. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.\n\n         19. Lactating or pregnant\n\n         20. Unwilling or unable to participate in all required study evaluations and procedures.\n\n         21. Unable to understand the purpose and risks of the study and to provide a signed and\n             dated informed consent form (ICF) and authorization to use protected health\n             information (in accordance with national and local subject privacy regulations).
Unequivocal demonstration of distant metastases (M1 disease)
Measureable disease
Disease that is suitable for local therapy administered with curative intent
Disease is suitable for local therapy administered with curative intent
Patient has valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
Have rapidly progressing disease, as judged by the investigator (e.g., rapid progression through prior treatment[s])
Indication for treatment as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines:\r\n* Massive (i.e. > 6 cm below the left costal margin) or progressive/symptomatic splenomegaly OR\r\n* Massive lymph nodes or nodal clusters (i.e. > 10 cm in longest diameter), or progressive/symptomatic lymphadenopathy OR\r\n* Presence of disease-related constitutional symptoms\r\n** Weight loss >= 10% over the preceding 6 months\r\n** Significant fatigue (i.e., Eastern Cooperative Oncology Group [ECOG] performance status [PS] 2 or worse; inability to work or perform usual activities)\r\n** Fevers higher than 100.5° Fahrenheit (F) or 38.0° Celsius (C) for 2 or more weeks without other evidence of infection\r\n** Night sweats for more than 1 month without evidence of infection\r\n* Progressive lymphocytes with an increase of >= 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia\r\n* Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
Documented progressive (clinical and/or objective) disease after the most recent systemic therapy regimen
History of or current major gastrointestinal, pulmonary, cardiovascular, genitourinary or hematologic disease, CNS disorders, infectious disease or coagulation disorders as determined by the Investigator
Bone-only disease and/or disease that cannot be biopsied.
The patient must have BCG refractory or recurrent non-muscle invasive bladder cancer\r\n* Refractory disease is defined as evidence of persistent high risk bladder cancer (high grade Ta, T1 and/or CIS) at the first cystoscopic exam after the initial 6 week induction course of BCG or at the 6 month cystoscopic exam\r\n* Recurrent disease is defined as reappearance disease after achieving a tumor- free status by 6 months following a full induction course of BCG with or without maintenance BCG; participants must have recurred with high grade and/or invasive disease within 18 months following the last dose of BCG\r\n** Low-grade superficial (Ta) disease will not be considered recurrent\r\n** Patients must exhibit disease recurrence receiving some form of standard intravesical therapy that must include a minimum of one induction course of BCG and may also include prior exposure to mitomycin, interferon, single agent gemcitabine or taxane therapy or maintenance
Steroid dependent or refractory classic chronic GVHD disease.
Progressive underlying malignant disease including post-transplant lymphoproliferative disease.
Patient has relapsed or relapsed/refractory multiple myeloma (MM);\r\n* Relapsed is defined as the development of disease progression following the achievement of stable disease (SD) or better to the most recent anti-MM regimen\r\n* Refractory is defined as experiencing less than a partial response (PR) to or progressive disease (PD) within 6 months after completion of the most recent anti-MM regimen
Patients must be three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
Untreated or previously treated for Waldenström's macroglobulinemia. Previously treated subjects must have either documented disease progression or had no response (stable disease) to the most recent treatment regimen.
Histologically confirmed metastatic and/or unresectable GIST; patients must demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line and beyond); any number of previous therapies for GIST is allowed; failure of imatinib is defined as either prior intolerance to imatinib therapy or prior progression of disease on imatinib in the metastatic setting or progression during adjuvant imatinib, or within 3 months of completing adjuvant imatinib; failure of sunitinib and regorafenib is defined only as prior progression of disease on sunitinib or on regorafenib as assessed by the investigator
Major inclusion criteria:\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of ?2\n\n          -  Pathologically confirmed relapsed/refractory DLBCL\n\n          -  Subjects must have ?1 measurable disease site on CT scan (? 1.5 cm in longest\n             dimension).\n\n          -  Adequate hepatic and renal function:\n\n               -  AST or ALT ?2.5 x ULN\n\n               -  Serum Creatinine ? 2.0 mg/dL and creatinine clearance ?60 mL/min/1.73\n\n               -  Bilirubin ?1.5 x ULN\n\n          -  Adequate hematologic function:\n\n               -  ANC >1,000 cells/mm3\n\n               -  Platelets ?75,000 cells/mm3\n\n               -  Hemoglobin ?8.0 g/dL\n\n               -  Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be\n                  ?1.5 x the upper limit of the normal range (ULN)\n\n          -  Must be registered into the Revlimid REMS™program and be willing to comply with the\n             requirements of Revlimid REMS™.\n\n        Major Exclusion Criteria:\n\n          -  Known central nervous system lymphoma\n\n          -  Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2\n             weeks\n\n          -  Radio- or toxin-immunoconjugates within 10 weeks\n\n          -  Prior allogenetic stem cell (or other organ) transplant within 6 months or any\n             evidence of active graft-versus-host disease or requirement for immunosuppressants\n             within 28 days prior to first dose of study drug
Subject has relapsed/refractory disease with an indication for treatment
Subject has refractory disease or developed recurrence after therapy with a BCR PI
Extramedullary disease only.
Patients must have had therapy with a proteasome inhibitor and lenalidomide and be refractory to lenalidomide according to the International Myeloma Working Group (IMWG) criteria definition of refractory disease (progressive disease on or within 60 days of stopping lenalidomide)
Disease progression at study entry
Known leptomeningeal disease
Relapsed or refractory disease
No evidence of disease at the time of registration, including no clinical concern for disease recurrence based on each of the following:\r\n* No evidence of disease by history and physical exam\r\n* Cancer antigen (CA)125 within normal limits\r\n* Computed tomography (CT) abdomen/pelvis demonstrating no radiological evidence of disease performed after completion of chemotherapy =< 28 days before entering study
Leptomeningeal disease
Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease
Patients with treated, non-progressive epidural disease are eligible
Concurrent medical condition which may increase the risk of toxicity, including:\r\n* Hypercalcemia of any cause\r\n* Untreated hyperparathyroidism\r\n* Paget’s disease of bone
Patients must have documentation of a new or progressive lesion on a radiologic imaging study performed within 6 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 6 months prior to study enrollment; note: this assessment will be performed by the treating investigator; evidence of progression by RECIST criteria is not required
Documented relapse or progressive disease on or after any regimen (subjects refractory to the most recent regimen are eligible)
Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.
Patients with treated, non-progressive epidural disease are eligible
Patients must not have had progression of disease on lenalidomide 25 mg; stable disease on lenalidomide is permitted
AT THE TIME OF PROCUREMENT: Nasopharyngeal carcinoma in first or subsequent relapse or with primary refractory disease
AT THE TIME OF INFUSION: Nasopharyngeal carcinoma in first or subsequent relapse or with primary refractory disease
Chronic renal disease / failure
Has met at least one of the following indications for treatment:\r\n* Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets < 100 x 10^9/L)\r\n* Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly\r\n* One or more of the following disease-related symptoms:\r\n** Weight loss >= 10% within the previous 6 months\r\n** Grade 2 or 3 fatigue attributed to CLL\r\n** Fevers > 100.5 Fahrenheit (F) for 2 weeks without evidence of infection\r\n** Clinically significant night sweats without evidence of infection\r\n* Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a two-month period or an anticipated doubling time of less than six months
Patients who previously received radiotherapy to the primary site with CT evidence of disease progression at the primary site within 3 months following the initial radiotherapy
Known castration-resistant disease
Subjects have active disease meeting the IWCLL 2008 published criteria.
Castration-resistant disease defined as:
First diagnosis of GBM with resectable disease (Cohorts 1c Part A only)
Patient’s current disease state must be one for which there is no known curative therapy
Prior vaccination with BCG for tuberculosis disease
Patients with HER2 positive disease.
Disease progression on or within 60 days of completion of the last therapy
Progressive disease on androgen deprivation therapy
Leptomeningeal disease
Patients with leptomeningeal disease are excluded
Soft tissue disease progression as defined by RECIST 1.1
Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable)
Disease that has relapsed or was refractory after prior chemo-immunotherapy
Participants with synchronous bilateral invasive disease are eligible only if both lesions are HER2-positive
Patients must have relapsed or relapsed and refractory disease after receiving 2 or more lines of therapy\r\n* Relapse is the occurrence of any of the following: 1) > 25% increase in in myeloma protein (M-protein) from the baseline levels; 2) reappearance of M-protein that had disappeared; or 3) definite increase in the size and number of lytic bone lesions recognized on radiographs (compression fractures per se do not constitute a relapse)\r\n* Subjects will be considered refractory to therapy, as defined by progression during treatment or within 60 days after the completion of salvage treatment; subjects with primary refractory disease, defined as disease that is non-responsive in patients that have never achieved a minor response or better with any therapy are excluded; this includes: 1) non-responding, non-progressing; patients who never achieve minor response (MR) or better in whom there is no significant change in M protein and no evidence of clinical progression; and 2) progressive; primary refractory, progressive disease where patients meet criteria for true progressive disease
Participants with primary refractory disease
Pathologically confirmed adenocarcinoma of the pancreas; patients have resectable borderline resectable disease, or unresectable disease with no evidence of distant metastases or peritoneal disease; the maximum dimension of the tumor must be =< 10 cm
All malignant disease must be able to be encompassed within a single irradiation field
All patients must have radiographically assessable disease
Patients who have active local-regional disease prior to registration
Patients must have disease amenable to biopsy at the time of enrollment as biopsies are required for study participation
May have previously received lapatinib as part of a regimen in the perioperative or metastatic setting with evidence of progression of disease; washout period for lapatinib of 14 days
Concurrent radiotherapy is not permitted for disease progression on treatment on protocol, but might be allowed for pre-existing non-target lesions with approval from the principal investigator of the trial
Disease progression as defined by International Myeloma Working (IMW) Criteria on the combination of carfilzomib, lenalidomide and dexamethasone (patients with progression on lenalidomide maintenance after completion of carfilzomib, lenalidomide and dexamethasone combination therapy will be eligible)
Disease progression on daratumumab
Intrathoracic disease should be encompassable in acceptable radiation fields per investigator clinical judgement.
Patient with extensive systemic disease and without reasonable systemic treatment options.
Site of disease amenable to low-dose, local radiotherapy (2 x 2Gy)
History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration
History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis
Subjects with T3 or higher, and N3 disease
Patients experiencing a visceral crisis including severe organ dysfunction as assessed by > grade (Gr) 2 symptomatic toxicities, laboratory studies, and/or rapid progression of disease originating from visceral metastasis
Symptomatic local or regional disease requiring medical intervention
Extrahepatic metastases including nodal disease
Diagnosis of Gilbert's disease
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or thallium scanning, MR spectroscopy or surgical/pathological documentation of disease
Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
Patients must have surgically resectable disease, in the opinion of the treating physician
Subjects must have documented IDH2 gene-mutated disease:
Patients may be on other systemic chemotherapies if progressive CNS disease occurs while on these treatments; NOTE: new systemic chemotherapies should not be started unless required to treat systemic disease and should not start until at least 1 follow up imaging study has been performed
Patients with leptomeningeal disease are not eligible for participation
Patients with leptomeningeal disease
Due to risk of disease exacerbation patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
Patients must have measured disease, defined as at least 1 cm x 1 cm of contrast enhancing disease
May include prior auto-SCT but not prior allo-SCT Patients who have failed second or third line therapy and beyond, such as DPACE, and who are experiencing a partial response rather than progressive disease are also eligible.
Patients must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease on study entry, serum free kappa or lambda light chain levels, or the serum free light chain ratio may be measured and used for disease monitoring if abnormal.
Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
Immunocompromised status due to:\r\n* Human immunodeficiency virus (HIV) positivity\r\n* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease; patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed\r\n* Other immunodeficiency diseases
For the dose-finding phase, patients may have stable disease OR progression of disease on the most recent treatment; for the expansion phase, patients must also have stable disease OR progression of disease on the most recent treatment; progression of disease is defined as new or worsening disease on objective imaging; progression or disease includes recurrence diagnosed while on adjuvant letrozole or exemestane
Patients with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria; central confirmation is needed for any site of disease that is tested to be HER2-positive by local testing (unless testing was done by Clarient)
Disease must be technically amenable to transhepatic arterial chemoembolization (TACE), radiofrequency ablation (RFA), or cryoablation; each case will be discussed at gastrointestinal (GI) tumor board with interventional radiology; patients must have evaluable disease
Participants must have received =< 12 months of prior chemotherapy for this disease without evidence of progressive disease with treatment; participants may have received prior radiotherapy provided approval has been obtained from the principal investigator (PI); participants with a history of radiation who have a platelet count < 150,000 due to radiation (disease, chemo, and other factors have been ruled out) will be excluded from this study
Progressive disease on prior treatment
Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study.
Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment.
Concurrent use of somatostatin analogs (SSTa) is allowed, provided that the patient is on a stable dose for at least two months and progressive disease on somatostatin analog has been documented; progression on octreotide is required for patients with tumors arising in the midgut
Prior treatment with sorafenib as single agent or in combination, with no less than 200 mg once every other day dose of sorafenib, with radiologic evidence of progression of disease
No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude
Pre-existing carotid artery disease
Disease which is amenable to curative local therapy
Patients must have measurable disease per RECIST 1.1 criteria defined as at least one lesion that can be accurately measured in at least one dimension, and that has not been the target of local or regional therapy including transarterial chemoembolization, intra-arterial chemotherapy, ethanol or radiofrequency ablation
Was not removed from carfilzomib therapy for progressive disease nor experienced progressive disease within 6 months after any prior carfizolmib therapy
They must have recurrent melanoma with measurable or evaluable sites of disease, 1.0 cm or larger, in order to assess the response to treatment by the immune-related response criteria (irRC)
Patient must have documented disease progression, and date of last documented disease progression must be within 12 months from date of randomization
Chemoembolization is allowed if >= 4 weeks from study entry; there are 3 possible scenarios:\r\n* If patient has hepatic disease only: they need to have progressed in the liver since chemoembolization and have measureable disease by RECIST 1.1 in order to be eligible\r\n* If patient has hepatic and extrahepatic disease: they will need to have progressed inside OR outside the liver and have measureable disease by RECIST 1.1 in order to be eligible
Acute or chronic pancreatic disease
For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
Patients with metastatic disease involving viscera or bones are ineligible; patients with extensive nodal involvement alone classified as stage IV disease, are eligible
Concomitant malignancies or previous malignancies with less than 2 years disease-free interval at the time of enrollment
Refractory NSCLC: Defined as achieving less than a complete response and having residual measurable disease by RECIST criteria after prior treatment with chemotherapy, targeted or small molecules, monoclonal antibodies or any combination of these.
Progressive disease during preoperative systemic therapy
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Disease confined to the intraperitoneal and retroperitoneal cavity; Note: nodal disease below the diaphragm, implants adherent to the surface of the liver or intrahepatic lesions will not be exclusionary; patients remain eligible if all intrahepatic tumor is debulked or ablated by the time treatment is initiated
Less than 2 years between last therapy and progression (e.g. most recent progression free interval < 2 years)
Currently have no clinical evidence of disease
Infratentorial, or leptomeningeal evidence of recurrent disease
Patients must have progressive disease within the thirteen months prior to study enrollment; progressive disease is as defined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, which is at least a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5 mm; the appearance of one or more new lesions is also considered progressive disease
Patients must have disease that is refractory (unresponsive) to radioactive iodine (RAI) treatment as defined by one of the following: \r\n* One or more measurable lesions that do not demonstrate RAI uptake \r\n* One or more measurable lesions progressive by RECIST 1.1 within 12-months of prior RAI therapy and/or the appearance of one or more new lesion within 12 months of prior RAI therapy\r\n* Cumulative RAI dose of > 600 mCi\r\n* Measureable disease that is fludeoxyglucose (18F) positron emission tomography (PET) scan positive
Objective evidence of disease progression (clinical or radiological) during or after at least 1 (V600 Wildtype) or at least 2 (V600 mutation positive) prior treatment regimens
Symptomatic or untreated leptomeningeal disease
Age criteria:\r\n* High dose TBI regimen: 6 months to =< 45 years \r\n* Middle intensity TBI regimen: 6 months to =< 65 years\r\n* Conditioning regimen selection should be based on the underlying disease, presence of minimal residual disease (MRD), age, co-morbidities, attending physician, and site preference; conditioning regimen will not require stratification of the randomization due to heterogeneity in the cohort of eligible patients.
Patient's disease must show extracapsular spread (ECS) in their nodal metastasis
Patient must have > 10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics
Patients enrolled on the randomized portion of the study must have had disease progression on abiraterone or enzalutamide
Surgically rendered free of disease no more than 12 weeks before randomization.
DISEASE AND PRIOR STATUS CRITERIA:
Relapsed disease or development of other malignancies
No extrapancreatic disease
Known cerebral or meningeal disease
Patients who have received prior locoregional therapy for metastatic disease including surgical resection, microwave ablation, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, or radiation are eligible providing the measurable disease is clearly manifest and is outside of the radiation port or ablation field; patients who have received liver directed treatments such as yttrium-90 radioembolization or transarterial chemoembolization are eligible if their measurable disease is outside of the liver
Rapidly progressive disease as judged by the investigator (examples include rapidly deteriorating performance status or symptomatic lymphangitic spread)
Patients with dermal change indicative of lymphedema or phlebolymphedema. disease.
Patients with concomitant disease know to get influence on bone metabolism
Patients with uncontrolled acute or chronic GVHD or refractory disease not responding to conventional therapy
Patients who have evidence of disease progression before day 100 after ASCT
Patients must have evaluable disease for response
Patients with leptomeningeal disease
If recent mold infection (e.g. Aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by infectious disease
Have discontinued lenalidomide due to any treatment-related adverse event or be refractory to any dose of lenalidomide. Refractory to lenalidomide is defined as either, participants whose disease progresses within 60 days of lenalidomide, or participants whose disease is nonresponsive while on any dose of lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an minimal response (MR) or development of progressive disease (PD) while on lenalidomide
Disease amenable to core biopsy; patients with pulmonary metastases as their only site of disease may enroll on this trial and will not undergo biopsy
Subject had no response (i.e., stable disease only) to first-line therapy with R-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP) or an equivalent regimen;
Relapsed or Relapsed/Refractory MM with progressive disease (PD) according to IMWG.
Bulky disease (defined as a mass measuring > 7.5 cm or one-third the maximal diameter of the thoracic cavity)
Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML);
Progressive disease as measured via RECIST 1.1 following EGFR-TKI therapy (with =< 5 sites of disease amenable to SRS or other locally-ablative treatment)
Inclusion Criteria:\n\n        Primary tumour characteristics:\n\n          1. Histological proof of newly diagnosed primary adenocarcinoma of the rectum\n\n          2. Locally advanced tumour fulfilling at least one of the following criteria on pelvic\n             MRI indicating high risk of failing locally and/or systemically (T4a, i.e. overgrowth\n             to an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum,\n             pelvic floor or side wall (according to TNM version 5), cT4b, i.e. peritoneal\n             involvement, extramural vascular invasion (EMVI+). N2, i.e. four or more lymph nodes\n             in the mesorectum showing morphological signs on MRI indicating metastatic disease.\n             Positive MRF, i.e. tumor or lymph node < 1 mm from the mesorectal fascia. Enlarged\n             lateral nodes, > 1 cm (lat LN+)\n\n        Exclusion Criteria:\n\n          1. Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve\n             roots indicating that surgery will never be possible even if substantial tumour\n             down-sizing is seen\n\n          2. Presence of metastatic disease or recurrent rectal tumour\n\n          3. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer\n             (HNPCC), active Crohn¡¦s disease or active ulcerative Colitis\n\n          4. Concomitant malignancies, except for adequately treated basocellular carcinoma of the\n             skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must\n             be disease-free for at least 5 years\n\n          5. Known DPD deficiency\n\n          6. Any contraindications to MRI (e.g. patients with pacemakers)\n\n          7. Medical or psychiatric conditions that compromise the patient's ability to give\n             informed consent\n\n          8. Concurrent uncontrolled medical conditions\n\n          9. Any investigational treatment for rectal cancer within the past month\n\n         10. Pregnancy or breast feeding\n\n         11. Patients with known malabsorption syndromes or a lack of physical integrity of the\n             upper gastrointestinal tract\n\n         12. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure,\n             symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation,\n             even if controlled with medication) or myocardial infarction within the past 12 months\n\n         13. Patients with symptoms or history of peripheral neuropathy
Gynecologic Cancer Intergroup (GCIG)-defined CA125 progression and absence of disease upon imaging or small-volume asymptomatic disease upon imaging and who have progressed following one, two or three lines of chemotherapy for recurrent disease
Permanent discontinuation of GSK2110183 in the parent study due to toxicity or disease progression.
DISEASE-SPECIFIC EXCLUSIONS:
Life-threatening visceral disease or other severe concurrent disease
Known active hyperparathyroid disease or other serious disturbance of calcium metabolism in the past 5 years
Patients with clinical evidence of disease beyond the uterus, including presence of suspicious aortic or inguinal nodes on imaging or clinical exam
Patients are eligible if they have stage III or IV disease; patients with stage 0, I or II disease will be eligible if they have evidence of active disease defined as one or more of the following signs/symptoms:\r\n* Documented weight loss of >= 10% over a six month period \r\n* Febrile episodes of 38 degrees Celsius (100.5 degrees F) or greater for greater than 2 weeks without evidence of infection \r\n* Massive or progressive splenomegaly defined as > 6 cm below the left costal margin \r\n* Massive (> 10 cm in longest diameter) or progressive lymphadenopathy
Individuals who do not meet criteria for cohort 1 (progressive disease) or cohort 2 (eligible for surgery) are not eligible for enrollment (i.e. patients with previously untreated disease that is not amenable/planned for surgical resection are not eligible)
Participants must have met all criteria to be enrolled on the main protocol for receipt of neratinib; at the time of enrollment on the extension phase for cohorts 1 and 3, patients must have experienced progression of non-CNS disease by RECIST 1.1 criteria
Patients must have measurable disease; patients with a diagnosis of neuroblastoma with Iobenguane (MIBG) avid disease only are permitted to enroll on this study
Patients with neoplastic lesions in the brainstem, cerebellum or spinal cord, radiological evidence of active (growing) multifocal disease, or leptomeningeal disease will be excluded; patients with evidence of diffuse subependymal disease or tumor in the brainstem, cerebellum, spinal cord, or cerebrospinal fluid (CSF) will also be excluded\r\n* Patients with radiological evidence of active (growing) multifocal disease, tumors extending into or crossing the corpus callosum or leptomeningeal disease, will be excluded
Known cerebral/meningeal disease
Scleroderma or active connective tissue disease
Must have evidence of progressive disease within 12 months of study entry
Disease progression prior to randomization
Require radiation therapy for palliation of symptoms or to prevent local progression of disease and associated complications and/or symptoms from metastases
Extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or disease that is considered by the investigator to be rapidly progressing or life threatening (eg, subjects who are intended for chemotherapy)
Patients must not have any disease that will obscure toxicity or dangerously alter Drug metabolism
Patients with more than 2 (i.e., 3 or greater) uncontrolled or untreated extracranial sites of gross disease
Acute or chronic pancreatic disease
Documented fungal disease that is progressive despite treatment
Permanent discontinuation of GSK1120212 in the parent study due to toxicity or disease progression.
Acute or chronic renal disease or pancreatitis
Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs.
No evidence of relapse or progression of underlying disease (molecular evidence of relapse/progression or mixed chimerism is permitted)
E 11. Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented cerebrospinal fluid (CSF) cytology; NOTE: discrete dural metastases are permitted
Patients with evidence of active thromboembolic disease, recent history of thromboembolic disease within the past 6 months, or risk factors for thromboembolic disease (excluding thrombosis of a central line)
Patient must have radioiodine refractory disease as defined by one or more of the following conditions:\r\n* All cases of medullary thyroid carcinoma\r\n* No iodine-uptake on a post-radioactive iodine treatment scan (in presence of low iodine diet and thyroid stimulating hormone [TSH] suppression) in an anatomically defined lesion that qualifies as target lesion by RECIST criteria, OR\r\n* If there is demonstrable iodine-uptake: the last radioiodine therapy of (>= 100 mCi) was given within the last 16 months OR if given more than 16 months before enrollment, there is evidence of disease progression after each of the last two radioiodine treatment performed within 16 months of each other (each dose should be >= 100mCi), OR\r\n* If the patient has received the maximum cumulative life time dose of radioactive iodine treatments of at least 600 mCi\r\n* If the patient declines or is intolerant of radioiodine therapy or if with progressive disease that is, in the opinion of the treating physician, likely to benefit from biologic therapy rather than further iodine therapy e.g. patient with heavy burden of disease
Local disease at the primary site must be asymptomatic
Permanent discontinuation of GSK2118436 in the parent study due to toxicity or disease progression
Patients must not have intra-operative evidence of T4b disease
Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bony disease
Patient who shows evidence of progressive disease during salvage chemotherapy or following ASCT
Subjects must have active disease appropriate for therapy
Maximum of number of lesions per patient will be 5 total for all disease sites
Unilateral adrenal disease
Untreated N3 mediastinal nodal disease
Unifocal breast cancer (no evidence of gross multifocal disease, multicentric, or bilateral disease)
Patients with Paget’s disease of the nipple
Inclusion Criteria\n\n        Subjects eligible for enrollment in the study must meet all of the following criteria:\n\n          1. Signed written informed consent. In Korea and Japan, subjects who are between >=18 and\n             <20 years of age must also have a legal representative sign the written informed\n             consent.\n\n          2. Post-menopausal female subjects >=18 years of age. Post-menopausal as defined by any\n             of the following:\n\n               -  Subjects at least 60 years of age.\n\n               -  Subjects under 60 years of age and amenorrhic for at least 12 consecutive months\n                  AND follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal\n                  range (utilizing ranges from the local laboratory facility).\n\n               -  Prior bilateral oophorectomy.\n\n               -  Prior radiation castration with amenorrhea for at least 6 months\n\n          3. Subjects must have a history of histologically confirmed breast cancer, with a\n             clinically confirmed diagnosis of metastatic disease [confirmed by histology, cytology\n             or other clinical means (e.g. CT, MRI)]. Subjects may have either measurable or\n             non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)\n\n          4. Tumors that are ER+ and/or PgR+ by local laboratory\n\n          5. Documentation of HER2 overexpression or gene amplification, in the invasive component\n             of either the primary tumor or metastatic disease site as defined as:\n\n               -  3+ by Immunohistochemistry (IHC) and/or\n\n               -  HER2/neu gene amplification by fluorescence, chromogenic or silver in situ\n                  hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH,\n                  CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ?2.0]\n\n          6. Subject must have received at least one prior regimen containing trastuzumab in\n             combination with chemotherapy for breast cancer:.\n\n               -  Subject has ONLY received prior trastuzumab in combination with chemotherapy as\n                  neoadjuvant and/or adjuvant treatment. OR\n\n               -  Subject has received ONE prior trastuzumab-containing regimen for metastatic\n                  disease (and has progressed), and may or may not have received prior trastuzumab\n                  in combination with chemotherapy as neoadjuvant and/or adjuvant treatment.\n\n          7. Subject must have received prior endocrine therapy (such as aromatase inhibitors or\n             selective estrogen receptor modulators). 8. Subjects who have a life expectancy of > 6\n             months as assessed by the treating investigator\n\n        9. Subjects must have baseline Left Ventricular Ejection Fraction (LVEF) ?50% measured by\n        echocardiography (ECHO) or multi-gated acquisition scan (MUGA) 10. Subject must have an\n        ECOG performance status of 0-1 11. All prior treatment related toxicities must be CTCAE\n        (Version 4.0) ? Grade 1 at the time of randomization 12. Completion of screening\n        assessments 13. Adequate baseline organ function. 14. Subjects must meet all of the\n        following criteria:\n\n          -  QTc <450msec or\n\n          -  QTc <480msec for subjects with bundle branch block The QTc is the QT interval\n             corrected for heart rate according to either Bazett's formula (QTcB) or to\n             Fridericia's formula (QTcF), machine or manual over read, for males and females. The\n             specific formula that will be used in a protocol should be determined prior to\n             initiation of the study, and the formula used to determine inclusion and\n             discontinuation should be the same throughout the study. The QTc should be based on\n             single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a\n             brief recording period\n\n        Exclusion criteria:\n\n          1. History of another malignancy. Exception: Subjects who have been disease-free for 5\n             years, or subjects with a history of completely resected non-melanoma skin cancer or\n             successfully treated in situ carcinoma are eligible.\n\n          2. Subjects with extensive symptomatic visceral disease including hepatic involvement and\n             pulmonary lymphangitic spread of tumor, or the disease is considered by the\n             investigator to be rapidly progressing or life threatening (subjects who are intended\n             for chemotherapy)\n\n          3. Serious cardiac illness or medical condition including but not confined to:\n\n               -  Uncontrolled arrhythmias\n\n               -  Uncontrolled or symptomatic angina\n\n               -  History of congestive heart failure (CHF)\n\n               -  Documented myocardial infarction <6 months from study entry\n\n          4. Known history of, or clinical evidence of, central nervous system (CNS) metastases or\n             leptomeningeal carcinomatosis\n\n          5. Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease\n             (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones,\n             liver metastases or stable chronic liver disease per investigator assessment)\n\n          6. Have a concurrent disease or condition that may interfere with study participation, or\n             any serious medical disorder that would interfere with the subject's safety (for\n             example, active or uncontrolled infection or any psychiatric condition prohibiting\n             understanding or rendering of informed consent)\n\n          7. Have any clinically significant gastrointestinal abnormalities that may alter\n             absorption such as malabsorption syndrome or major resection of the stomach or bowels\n\n          8. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs\n             chemically related to any of the study agents or their excipients that, in the opinion\n             of the Investigator or GSK medical monitor, contraindicates their participation\n\n          9. Any prohibited medication.\n\n         10. Administration of an investigational drug within 30 days or 5 half-lives, whichever is\n             longer, preceding the first dose of study treatment.
Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
Multifocal disease or leptomeningeal spread
LVEF by ECHO or MUGA within institutional normal limits unless thought to be disease related; DLCO >= 60% with no symptomatic pulmonary disease unless thought to be disease related
If the subject received immunotherapy, the documented radiographic disease progression is required
COHORT 1 AND ACINIC CELL CARCINOMA PATIENTS IN COHORT 2 ONLY: Patients must have documentation of a new or progressive lesion on a radiologic imaging study performed within 6 months prior to study enrollment (progression of disease over any interval is allowed) and/or new/worsening disease related symptoms within 6 months prior to study enrollment; Note: this assessment will be performed by the treating investigator; evidence of progression by RECIST criteria is not required
Hepatocellular disease (eg, cirrhosis)
Rapidly progressive disease.
Unresectable disease or medically inoperable
Have received prior treatment for metastatic disease with oxaliplatin-based regimen and either:\r\n* Had disease progression OR\r\n* Had stable disease OR\r\n* Discontinued oxaliplatin due to neuropathy
Patients who have a diagnosis of Gilbert’s disease
Must have shown clinical characteristics of acquired resistance to enzalutamide or apalutamide defined as: decline in serum PSA ?50% compared to baseline serum levels by week 12 (±4 weeks) of enzalutamide or apalutamide treatment and before disease progression by PCWG3 PSA criteria, OR disease progression by PCWG3 radiographic criteria. (Part 2 only) Parts 1 and 2:
Has disease that is suitable for local therapy administered with curative intent
Evidence of distant disease or histologically-proven nodal metastases; patients with radiologic evidence of lymphadenopathy must have biopsy proof of N0 status
Patients must have unresectable disease as determined by the multidisciplinary evaluation or patient is not considered operable due to medical reasons
Patients who were determined to have a best clinical response of progressive disease with salvage treatment immediately prior to ASCT
For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
Neutrophils >= 0.5 x 10^9/L, unless cytopenias are deemed due to disease
Platelets >= 50 x 10^9/L, unless cytopenias are deemed due to disease
Active peptic ulcer disease
Patients with microscopic and/or gross extra thyroidal disease extension without RAI uptake but with a) FDG-PET positive disease or b) suppressed thyroglobulin >1 ng/mL or c) stimulated thyroglobulin >10 ng/L.
Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from being subjected to surgical excision
Women with non-invasive disease or microinvasion are not eligible
For pigmented villo-nodular synovitis (PVNS), patients must have a histologically confirmed diagnosis of inoperable progressive or relapsing PVNS, or resectable tumor requesting mutilating surgery, as well as demonstrated progressive disease in the last 12 months.
Patients who have undergone gross total resection and have no detectable residual disease are eligible
There is radiographic evidence of leptomeningeal disease prior to study entry
Positive clinical and radiologic assessments for local or regional recurrence of disease at the time of study entry.
Patients must have relapsing disease (patients with progressive disease will be excluded); in addition, patients must have had at least two relapses in the past 18 months; relapses are defined clinically or radiographically
Patients who have stable (SD) or responding disease (PR or CR) documented by the appropriate radiological, clinical, or laboratory assessments within 12 weeks before enrollment (Note: response criteria from the previous AG-013736 protocol should be used to determine stable or responding disease).
Patients must be expected to have disease controlled for at least 60 days after HCT
Active infectious disease concerns
Patients with aggressive lymphomas (such as DLBC) must not have bulky, rapidly progressive disease immediately prior to HCT
Patients who have ASM with eosinophilia and known positivity for the FIP1L1-PDGFR? fusion unless they have demonstrated relapse or disease progression on prior imatinib therapy
Isolated extramedullary disease
Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have measurable disease (at least one measurable lesion) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; NOTE: all sites of disease must be evaluated within 4 weeks prior to registration to treatment; patients must have a history of melanoma of one of the following subtypes: \r\n* Acral (as defined as occurring on the palms, soles, or subungual sites)\r\n* Melanoma arising from the vagina and/or vulva\r\n* Melanoma arising on other mucosal surface (not vagina or vulva)
Disease-free
Auto-immune disease
Patients with radiographic or cytologic evidence of leptomeningeal or multicentric disease will be excluded and replaced if needed
Platelets >= 20,000/mm^3; this requirement may be waived if patient has hematologic relapse of disease or if patient has not yet recovered counts from chemotherapy
Patients must not have: a) active infection; b) disease that will obscure toxicity or dangerously alter drug metabolism, especially liver disease; c) serious intercurrent medical illness; d) prior treatment with HDAC inhibitors. However, patients who have received anticancer agents for non-therapeutic purposes (for eg., as part of a pharmacology study without therapeutic intent) will remain eligible for enrollment into the study.
Burkitt or acute lymphoblastic lymphomas\r\n* High-risk disease in remission\r\n* Primary refractory disease\r\n* Recurrent disease\r\n* Relapse/progression after autologous HSCT
Cutaneous T-cell lymphomas (mycosis fungoides, Sezary syndrome)\r\n* >= Stage III\r\n* Disease progression >= 2 prior regimens, including at least one systemic therapy
Patients with cutaneous T-cell lymphomas (e.g. mycosis fungoides, Sezary syndrome) must have:\r\n* Stage III or greater disease\r\n* Disease which has progressed on or failed to respond to at least 2 therapies including one systemic therapy
TIER I SUBJECTS: Patients with relapsed follicular lymphoma with stable disease and no lymph node mass greater than 5 cm (in any one dimension) following at least two systemic chemotherapy and/or immunotherapy regimens; stable disease from pre-study regimen may be either a clinically determined response by the principal investigator or physician co-investigator member of the study team, or a measured response as per the response criteria of this protocol
Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis
Specific eligibility criteria stratum 1:\r\n* Disease status: \r\n** Radiographic disease progression as defined for stratum 3 (below) is not required for trial entry\r\n** Patient does not have clinical symptoms from the plexiform neurofibroma
Specific eligibility criteria stratum 2:\r\n* Disease status: \r\n** Radiographic disease progression as defined for stratum 3 (below) is not required for trial entry\r\n** Patient has clinical symptoms from the plexiform neurofibroma
Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator
Patients must have received at least one platinum-based chemotherapy for recurrent/advanced disease; recurrent disease is defined as having recurred after definitive therapy and advanced disease is defined as T4 and/or N2 and/or M1; in addition, for completion of Cohort #2, patients must also have received a tubulin inhibitor as part of their therapy for urothelial cancer; for purposes of this evaluation, treatment with chemotherapy regimens where carboplatin or similar is substituted for cisplatin or where a taxane is added or removed will be considered the same regimen; tubulin inhibitors in common use include paclitaxel, docetaxel, and vinblastine; the exception to this requirement applies to women
Any other disease requiring long-term corticosteroids or immunosuppressants
All stages of disease
Patients with evidence of disease are only eligible if the disease is stable (or persistent) in comparison to the status prior to transplantation
Evidence of relapse or progression of disease after transplantation
Patients may have CNS or other sites of extramedullary disease; no cranial irradiation is allowed during the protocol therapy
Patients must have at least ONE of the following: 1) Recurrent/progressive disease at any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease
Patients with disease of any major organ system that would compromise their ability to withstand therapy.
Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
Progressive disease despite ongoing androgen deprivation therapy.
Relapse of underlying malignant disease after allo-HSCT.
Clinically quantifiable disease burden defined as:
Group 1: Patients must have 1) both a and b below; and 2) at least one of c, d or e:\r\n* a. diffuse cutaneous scleroderma with skin score of greater than or equal to 16 (modified Rodnan scale [mRSS])\r\n* b. duration of systemic sclerosis less than or equal to 7 years from the onset of first non-Raynaud’s symptom\r\n* c. presence of interstitial lung disease (either forced vital capacity [FVC] or corrected diffusing capacity of the lung for carbon monoxide [DLCOcorr] less than 70 % of predicted) and evidence of alveolitis (abnormal bronchoalveolar lavage (BAL) or high resolution chest computed tomography [CT] scan) after treatment with intravenous cyclophosphamide greater than or equal 2 grams given over at least a 3 month period; for patients not able to adequately complete pulmonary function tests (PFT), there must be evidence of progressive disease on chest CT\r\n* d. left heart failure with left ventricular ejection fraction (LVEF) < 50% (that has responded to treatment targeted to scleroderma); 2nd or 3rd atrioventricular (AV) block with other evidence of cardiomyopathy related to SSc; myocardial disease not secondary to SSc must be excluded by a cardiologist \r\n* e. history of SSc-related renal disease that is not active at the time of screening; history of scleroderma hypertensive renal crisis is included in this criterion
Group 2: Progressive pulmonary disease as defined by a decrease in the FVC or DLCOcorr by 15 percent or greater compared to a prior FVC or DLCOcorr in the previous twelve month period; in addition, patients may have either less skin involvement than group 1 (mRSS less than 16) and the FVC or DLCOcorr is less than 70% or both FVC and DLCOcorr greater than or equal to 70% if they have diffuse cutaneous disease (mRSS greater than 16) at screening for the study; patients must also have evidence of alveolitis as defined by abnormal chest CT or BAL; for patients not able to adequately complete PFT, there must be evidence of progressive disease on chest CT
Known intra-cerebral disease or brain mets
Isolated extramedullary disease relapse
History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
Presence of extra-hepatic spread of disease.
Unstable coronary artery disease or recent myocardial infarct (i.e. within 1 year).
Life-threatening visceral disease or other severe concurrent disease
Dual refractory CMV reactivation to foscarnet and ganciclovir or evidence of CMV disease
Have progressive disease at the time of transplant
Refractory disease after first or greater relapse and a re-induction attempt, OR
Patients with will be eligible if they are either in partial response, or have stable disease after no more than two attempts of induction therapy
Histological or cytological diagnosis of ES-SCLC (Note: Extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or pericardial effusion or hematogenous metastases)
Leptomeningeal disease or carcinomatous meningitis
Patients who are expected to require any of the following therapies between enrollment and completion or discontinuation of the study treatment:\r\n* Immunosuppressive drugs, including corticosteroids, methotrexate, mercaptopurine, azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, ATG (anti-thymoglobulin), interleukin 2 (IL2)-receptor antibodies (basiliximab, daclizumab), tumor necrosis factor (TNF)-a antibodies (infiliximab, etanercept, adalimumab)\r\n* Radiotherapy for the target disease\r\n* Surgical therapy for the target disease
Severe (CTCAE v 4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease
No progressive disease at the time of initiation of maintenance therapy
Serum bilirubin =< 2.0 (unless hemolysis or Gilbert disease)
Histologically documented, epithelial ovarian, fallopian tube, or primary peritoneal, high grade serous or clear cell carcinoma are eligible; all patients must have a confirmed pathology; stage 3 and 4 initial disease with response to primary surgery and neo/adjuvant chemotherapy, platinum refractory disease, and patients with recurrent disease are candidates
The patient must have a life expectancy of 3 months or more based on the judgment of the investigators; women who have rapidly progressive symptomatic disease affecting major organ systems such as the liver and lungs will be excluded
Subject has been previously treated with enzalutamide for at least 8 months, and stopped enzalutamide due to progressive disease (not due to adverse events), followed by at least 4 cycles of docetaxel and/or cabazitaxel chemotherapy, with or without other intervening anti-cancer therapies (including but not limited to aminoglutethimide, ketoconozole, abiraterone acetate, Rad-223, or sipuleucel-T), prior to receiving chemotherapy. Note: for patients who receive sequential taxanes, there must not have been progressive disease upon ending the first taxane, or use of any anti-cancer agents between the two taxanes.
Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
Patients receiving any disease-modifying anti-rheumatic drug (DMARD)
Active or clinically symptomatic chronic pancreatitis or disease affecting pancreas
Documented progressive disease based on radiographic, clinical or pathologic assessment.
Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
Evidence of disease progression at study entry.
Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy
Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy
Evidence of relapsed disease by morphologic, cytogenetic or molecular diagnostic tools
Pre-existing carotid artery disease.
Active extramedullary disease at any site. (Note: Definitive therapy of known previous sites of extramedullary disease is allowed)
Progressive disease while receiving a BTKi therapy, or stable disease as best response after 12 months of receiving a BTKi therapy
Initial diagnosis of advanced stage disease must have occurred ? 6 weeks prior to starting Cycle 1 Day 1. NOTE: The clock for this time interval starts with the date of last evaluation confirming advanced disease (either biopsy or imaging results).
Radiologic documentation of disease progression
Coronary artery disease with angina limiting exercise capability
Joint disease limiting exercise capability
Any other severe concurrent disease, or serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo the proposed therapy
Patients with an active infectious disease
Inclusion Criteria:\n\n        For patients with solid tumors:\n\n          -  documented cKit-positive neoplasms\n\n          -  Patient must have progressive disease as defined by any of the following:\n\n          -  SCLC: patient has progressed after at least 1 prior therapy\n\n          -  GIST : patient has relapsed or has refractory disease, and no further approved\n             effective therapeutic option exists\n\n          -  Patients with other cKit-positive solid tumors: patient has progressed after at least\n             one prior line of therapy and no further approved effective therapeutic option exists\n\n          -  Patient has measurable disease as per RECIST v1.1 criteria\n\n        For patients with AML:\n\n          -  documented cKit-positive acute myelogenous leukemia\n\n          -  Consent to newly obtained bone marrow aspirate\n\n          -  Patient must have progressive disease defined as relapsed or refractory non-PML AML\n             following standard therapy or for whom no effective therapy exists.\n\n          -  Blast count < 50,000/mm3\n\n        Exclusion Criteria:\n\n        For patients with solid tumors:\n\n          -  Patient has central nervous system (CNS) metastatic involvement unless the CNS\n             metastases have been previously treated and the patient is clinically stable and on a\n             stable dose of corticosteroids for at least 4 weeks prior to enrollment.\n\n          -  Patient has the presence of other clinically significant hematologic, cardiac,\n             respiratory, gastrointestinal, renal, hepatic or neurological conditions.\n\n          -  Patient has a history of serious allergic reactions, which in the opinion of the\n             investigator may pose an increased risk of serious infusion reactions\n\n          -  Patient has been previously treated with cKit directed antibodies\n\n          -  Pregnant or nursing women\n\n        For patients with AML:\n\n          -  Patient has received prior allogeneic bone marrow transplant (BMT).\n\n          -  Patient has the presence of other clinically significant cardiac, respiratory,\n             gastrointestinal, renal, hepatic or neurological disease\n\n          -  Patient has a history of serious allergic reactions, which in the opinion of the\n             investigator may pose an increased risk of serious infusion reactions\n\n          -  Patient has been previously treated with cKit directed antibodies\n\n          -  Pregnant or nursing women
Creatinine =< 2 x upper limit of normal, unless there is known chronic kidney disease (CKD) (creatinine must be at baseline for subjects with chronic kidney disease)
Patients may enroll in this study if they are thought to have no residual disease after TURBT
Patients must have disease amenable to biopsy and must be medically fit to undergo a biopsy
Patients must have documented disease progression after receiving at least one prior therapeutic regimen (e.g. pralatrexate, romidepsin, bexarotene, vorinostat)
Progression of disease despite androgen ablation shown by objective, documented evidence of disease progression (excluding PSA).
Objective documented evidence of disease progression at study entry
Prior radiotherapy to disease sites is allowed with certain protocol-defined restrictions.
Any organ dysfunction thought to be secondary to disease will be considered separately and the patient will be included at the investigators discretion
CRPC subjects: Must have measurable disease by either: RECIST1.1 or a minimum PSA of 5 nanogram/milliliter; Disease progression on last line of therapy and must have progressed on abiraterone, enzalutamide, or taxane chemotherapy; Subjects may continue GnRH agonists; Small cell prostate cancer is eligible
Subjects with a history of prior radiotherapy are eligible if they meet the following parameters: Prior to study treatment administration, must be ? 21 days post-therapy and have recovered from all toxicities; must have evidence of measurable disease outside the radiation fields or radiologically confirmed progression of disease; must not have had > 25% of their functional bone marrow irradiated. Must have radiologically measureable disease, a life expectancy > 12 weeks, and adequate organ function.
-  Subjects with Philadelphia negative B-precursor ALL, with any of the following:\n\n               -  refractory to primary induction therapy or refractory to salvage therapy,\n\n               -  in untreated first relapse with first remission duration <12 months\n\n               -  in untreated second or greater relapse\n\n               -  relapse at any time after allogeneic HSCT\n\n          -  Subject has received intensive combination chemotherapy for the treatment of ALL for\n             initial treatment or subsequent salvage therapy.\n\n          -  Greater than 5% blasts in the bone marrow\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n        Exclusion Criteria\n\n          -  Malignancy other than ALL within 5 years before blinatumomab treatment, except for\n             adequately treated selected cancers without evidence of disease\n\n          -  Diagnosis of Burkitt's leukemia according to World Health Organization classification,\n             or human immunodeficiency virus (HIV), Hepatitis B or C, or other clinically\n             significant disorder\n\n          -  Current relevant central nervous system (CNS) pathology or known or suspected CNS\n             involvement\n\n          -  Isolated extramedullary disease\n\n          -  Current autoimmune disease or history of autoimmune disease with potential CNS\n             involvement\n\n          -  Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab\n             treatment, or eligibility for allogeneic HSCT at the time of enrollment\n\n          -  Active acute grade 2 to 4 graft versus host disease (GvHD) according to Glucksberg et\n             al (1974) criteria that required systemic treatment to prevent or treat GvHD 2 weeks\n             before blinatumomab treatment\n\n          -  Known exclusion criteria to investigator choice of SOC chemotherapy (per package\n             insert)\n\n          -  Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19\n             therapy) within 4 weeks of protocol-specified therapy\n\n          -  Abnormal laboratory values (alanine or aspartate transaminase [ALT or AST] or alkaline\n             phosphatase [ALP] ? 5 × upper limit of normal [ULN]; total bilirubin or creatinine ?\n             1.5 × ULN), or calculated creatinine clearance < 60 mL/min.
Current or recent (within 3 months of study drug administration) gastrointestinal disease such as chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g. infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting study treatment are not exclusionary
Progression was documented,
Unilobar disease
Evidence of any disease or condition that would place the patient at undue risk and preclude safe use of TheraSphere treatment
Presence of clinically and/or radiologically documented disease. At least one site of disease (which will not be removed during the course of the study) must be uni-dimensionally measurable as per RECIST 1.1 or clinically quantifiable (such as in the case of skin disease)
Disease amenable to biopsy and agree to undergo biopsy for molecular analysis
Documented disease progression during or following most first line therapy for advanced disease
Evaluable disease
At least 2 sites of disease\r\n* One for palpable for biopsy and treatment (if > 2 sites are present, the biopsy site can be different from the treatment site); if there is no palpable disease, ultrasound may be used for guidance and administration of SD-101\r\n* One measurable radiographically or by skin assessment
Active cytomegalovirus (CMV) disease at the time of enrollment
Clinical (e.g. multiple new cranial nerve deficits in the absence of obvious radiographic disease to explain symptoms) or radiographic evidence of leptomeningeal disease
History of histological confirmation for recurrent disease, or if recurrent disease is not readily accessible to biopsy, must have two consecutive carcinoembryonic antigen (CEA) or cancer antigen (CA) 19-9 increases, or positron emission tomography (PET) avidity
ENTRY CRITERIA:\n\n        DISEASE CHARATERISTICS:\n\n          -  Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at\n             least two different previous regimens.\n\n               -  Refractory disease is defined as progressive disease while on therapy or\n                  progression within 60 days of therapy.\n\n               -  Progressive disease is defined by a 25% increase from the lowest response value\n                  in specified tests.\n\n          -  Measurable disease as defined by at least one of the following:\n\n               -  Serum M-protein ? 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA)\n\n               -  Urine M-protein ? 200mg/24hours\n\n               -  Serum free light chains ? 10 mg/dL and abnormal kappa/lambda ratio\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No anti-myeloma treatments within 28 days before the start of study treatment.\n\n          -  Must have recovered from side effects of prior treatments.\n\n        PATIENT CHARACTERISTICS:\n\n        Age\n\n        • ? 18 years\n\n        Performance Status\n\n        • ECOG 0, 1, or 2\n\n        Bone Marrow Reserve\n\n          -  Absolute neutrophil count (AGC/ANC) ? 1,000/uL\n\n          -  Platelets ? 30,000/uL\n\n          -  Hemoglobin ? 8g/dL\n\n        Renal Function\n\n        • Glomerular Filtration Rate (GFR) > 45mL/min/1.73m^2\n\n        Hepatic Function\n\n          -  Total bilirubin ? 2.0 X ULN\n\n          -  AST, ALT, ALP ? 3.0 X ULN, or ? 5.0 X ULN (if liver metastases exist)\n\n        Cardiovascular\n\n          -  No congestive heart failure < 6 months\n\n          -  No unstable angina pectoris < 6 months\n\n          -  No myocardial infarction < 6 months\n\n          -  No history of ventricular arrhythmias\n\n          -  No history of supraventricular arrhythmias\n\n          -  No NYHA Class > II CHF\n\n          -  Normal Transthoracic Echocardiogram (TTE) is required for patients with history of EKG\n             abnormalities, CHF, coronary artery disease or other cardiac disease, or with a\n             history of having received adriamycin or doxorubicin\n\n          -  Patients with a left ventricular ejection fraction (LVEF) of less than 50% will be\n             excluded from study entry\n\n        Pulmonary\n\n        • Normal clinical assessment of pulmonary function\n\n        Other\n\n          -  Negative serum pregnancy test if female and of childbearing potential\n\n          -  Women who are not pregnant or nursing\n\n          -  Subjects, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study\n\n          -  No known autoimmune disease other than corrected hypothyroidism\n\n          -  No known prior organ allograft or allogeneic transplantation\n\n          -  Not HIV positive\n\n          -  No history or evidence of uncontrollable CNS disease\n\n          -  No psychiatric illness/social situation\n\n          -  No other illness that in the opinion of the investigator would exclude the subject\n             from participating in the study\n\n          -  Must provide informed consent and HIPPA authorization and agree to comply with all\n             protocol-specified procedures and follow-up evaluations\n\n          -  Active systemic infection requiring parenteral antibiotic therapy.\n\n          -  No ongoing chronic systemic steroid therapy required.
Recurrent disease with an:
Glioblastoma or gliosarcoma disease with leptomeningeal spread
Prior gastrectomy (partial or total) for the underlying malignant disease under investigation
If there is a history of prior malignancies other than those below, must be disease free for at least 5 years. Patients with malignancies listed below less than 5 years before study entry may be enrolled if they have received treatment resulting in complete resolution of the cancer and have no clinical, radiologic, or laboratory evidence of active/recurrent disease.
They must have recurrent melanoma with measurable or evaluable sites of disease, 1.0 cm or larger, in order to assess the response to treatment by the immune-related response criteria
SCREENING: Patients with clinically evident or histologically proven sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura who can be rendered no evidence of active disease (NED) following standard surgical therapy; note: patients with active disease outside the thorax may be eligible for the study once the extrathoracic disease is definitively treated by local modalities such as radiation, surgery, or radiofrequency ablation
Patients must have previously received at least one systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
Resection of all pTa/pT1 papillary disease
Disease refractory to either, AI, tamoxifen or fulvestrant
Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
Applicable disease criteria
Refractory to lenalidomide in the most recent line of therapy, as defined by the International Myeloma Consensus Panel criteria as failure to achieve minimal response or development of progressive disease while on lenalidomide or within 30 days of lenalidomide therapy
Patients with malignant pleural disease (MPD), pathologically confirmed at Memorial Sloan-Kettering Cancer Center (MSKCC) (radiographic confirmation is acceptable for screening phase eligibility), and defined as one of the following (patients who have not yet received treatment may enroll in the screening portion only):\r\n* Malignant pleural mesothelioma – previously treated with at least one prior treatment regimen\r\n* Non-small cell lung cancer metastatic to the pleura—previously treated with at least one prior treatment regimen (chemotherapy, surgery, or targeted agent) and documented progression of disease; patients with disease outside of the pleura will be discussed among study principal investigator (PI) and Co-Pls prior to considered eligible for the study; disease outside of the pleura must not require any immediate therapy per PI’s discretion\r\n* Breast cancer metastatic to the pleura— previously treated with at least one prior treatment regimen (chemotherapy, surgery or targeted agent) and documented progression of disease; patients with disease outside of the pleura will be discussed among study PI and Co-Pls prior to considered eligible for the study; disease outside of the pleura must not require any immediate therapy per PI’s discretion
Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within 28 days of Day 1 dosing with the following exceptions: a. Arm A: A minimum 5-day washout after discontinuation of ibrutinib therapy (or other BTK inhibitors) is required; only those subjects without rapid disease progression during the 5-day washout will be allowed to enroll into Arm A. i. Rapid disease progression is defined as follows:
Refractory post-ASCT i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed subjects) ii. If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy
Tumors clinically staged as unresectable disease
Evidence of disease progression on neoadjuvant chemo T
Patients with: a) active infection, b) disease that will obscure toxicity or dangerously alter drug metabolism, c) serious intercurrent medical illness, d) prior documented recurrence with temozolomide
Indication for treatment as defined by the National Cancer Institute (NCI) Working Group & International Workshop in CLL Guidelines (2, 3):\r\n* Massive (i.e. > 6 cm below the left costal margin) or progressive / symptomatic splenomegaly OR\r\n* Massive lymph nodes or nodal clusters (i.e. > 10 cm in longest diameter), or progressive / symptomatic lymphadenopathy OR\r\n* Presence of disease-related constitutional symptoms:\r\n** Weight loss >= 10% over the preceding 6 months \r\n** Significant fatigue (i.e., Eastern Cooperative Oncology Group [ECOG] performance status [PS] 2 or worse; inability to work or perform usual activities)\r\n** Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of infection\r\n** Night sweats for more than 1 month without evidence of infection OR\r\n* Progressive lymphocytosis with an increase of >= 50% over a 2-month period or an anticipated doubling time of less than 6 months OR\r\n* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and / or thrombocytopenia OR\r\n* Autoimmune anemia and / or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
If previously received lenalidomide, demonstration of clinical response of any duration or stable disease with progression-free interval of ?6 months from start of that therapy.
Extramedullary disease noted during pre-HCT work up can receive a boost of radiation as clinically indicated
“Relapsed or refractory” refers to patients who have received at least 1 prior treatment regimen for lymphoma (which may include prior autologous stem cell transplantation) and have demonstrated evidence of progressive disease by clinical and/or radiographic characteristics
Disease to be treated by ILI must be distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion); if provider feels ILI appropriate with disease in these areas, patients may be enrolled with principal investigator (PI) approval
Leptomeningeal disease as a manifestation of cancer
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Evidence of significant uncontrolled concomitant diseases, such as ocular toxicities, diabetes, cardiovascular disease; nervous system, renal, hepatic, endocrine, or gastrointestinal disorders; autoimmune disease, or a serious non-healing wound or fracture
Inclusion Criteria:\n\n        General:\n\n          -  Participants with solid tumors must have one or more metastatic tumors evaluable or\n             measurable on radiographic imaging\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (or 2 upon\n             approval by the medical monitor)\n\n          -  Life expectancy of greater than or equal to (>/=) 3 months\n\n          -  Disease-free of active second/secondary or prior malignancies >/= 2 years with the\n             exception of currently treated basal cell, squamous cell carcinoma of the skin, or\n             carcinoma \in-situ\ of the cervix or breast\n\n          -  Adequate hematological, renal, hepatic and coagulation laboratory test results\n\n          -  Women of child bearing potential and men must agree to use adequate contraception\n             during the study and for 4 months after the last dose of study drug\n\n        Advanced Solid Malignancies:\n\n          -  Participants with previously treated, histologically confirmed advanced solid\n             malignancy with progressive disease requiring therapy\n\n          -  Participants must be refractory or intolerant to standard therapy\n\n        NUT-midline carcinoma:\n\n          -  Participants with histologically confirmed newly diagnosed or relapsed/refractory NMC\n             with PD requiring therapy\n\n          -  Diagnosis of one of the following is required:\n\n               1. NUT Midline Carcinoma based on ectopic expression of NUT protein as determined by\n                  Immunohistochemistry (IHC) and/or;\n\n               2. Detection of NUT gene translocation as determined by Fluorescence In-Situ\n                  Hybridization (FISH) Advanced Aggressive DLBCL\n\n          -  Histologically confirmed advanced aggressive B-cell lymphoma with abnormal MYC\n             expression with persistent disease requiring treatment\n\n          -  Participants must have relapsed or progressed after at least 2 lines of prior therapy\n             and not eligible for any curative treatment\n\n          -  Participants must have measurable disease\n\n        Exclusion Criteria:\n\n          -  Participants with hematologic malignancies\n\n          -  New York Heart Association Class III or IV, cardiac disease, myocardial infarction\n             within the past 6 months, unstable arrhythmia\n\n          -  Have Fridericia-corrected QT interval (QTcF) greater than (>) 470 milliseconds (msec)\n             (female) or > 450 (male), or history of congenital long QT syndrome\n\n          -  Active, uncontrolled bacterial, viral, or fungal infections\n\n          -  Known clinically important respiratory impairment\n\n          -  Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen, or\n             hepatitis C antibodies\n\n          -  History of major organ transplant\n\n          -  History of an autologous or allogeneic bone marrow transplant. For DLBCL participants\n             only: DLBCL participants may have had a previous autologous transplant but not within\n             90 days of study entry\n\n          -  Symptomatic central nervous system malignancy or metastasis\n\n          -  Pregnant or nursing\n\n          -  Treatment with surgery or chemotherapy within 28 days prior to study entry\n\n          -  Prior treatment with small molecule (BET) family inhibitor\n\n          -  Radiation for symptomatic lesions within 14 days of study enrollment
Stage 1-3 tumors > 1 cm in maximal diameter, any nodal status, multifocal or multi-centric disease is permitted, no evidence of distant metastases
Have preexisting corneal disease that may interfere with assessment for potential eye toxicity during the study.
Leptomeningeal disease
History of renal disease or current evidence of renal disease
Meaurable or evaluable extra-cranial disease as defined by RECIST v 1.1
CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation demonstrates stable disease
Leptomeningeal disease as a manifestation of cancer
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
CNS disease requiring immediate neurosurgery intervention (e.g., resection, shunt placement, etc.)
Life-threatening visceral disease or other severe concurrent disease
Patient's current disease state must be one for which there is no known curative therapy
Scarring or significant skin disease on both upper arms.
Radiographic evidence of disease
Acute or chronic viral, bacterial immune or other disease associated with abnormal immune function
Either complete disappearance of all lesions, or persistence of metastatic disease (stable disease) without unequivocal progression or the occurrence of new lesions
Measureable disease per RECIST v1.1 prior to administration of study medication
Patients with nodal disease are eligible
Patients with visceral disease are ineligible
Confirmed diagnosis of refractory celiac disease Type 2 (RCD-II)
Transaminases =< 2 x ULN, except in known hepatic disease, wherein may be =< 5 x ULN
Systemic sites of disease need to be stable on systemic therapy based on the most recent (within 12 weeks) staging scans
Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not be candidates for therapy of proven efficacy for their disease.
RAI-refractory disease on structural imaging
Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (=< 5 discrete lesions of disease irrespective of location, inclusive of the primary lesion):\r\n* All sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology\r\n* All intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion\r\n* Each brain metastasis is included as a distinct lesion\r\n* Patients already started on erlotinib are eligible as long as their sites of disease are determined to be eligible for definitive local therapy by consensus of the principal investigators within 12 weeks of the patient first taking erlotinib
Leptomeningeal disease
Has evidence of disease progression under Protocol 8400-401.
Objective evidence of disease progression on study entry
Study patients must have disease that is amenable to pre and post treatment biopsy and be willing to undergo this
Symptomatic or untreated leptomeningeal disease
Recurrent disease or second primary lung cancer (only de novo IIIA disease allowed)
Documented IDH2 gene-mutated disease based on local site testing
In subjects with AITL, evidence of meningeal or cerebral disease or a history of progressive multifocal leukoencephalopathy
Response to previous RELHEM2 treatment: at least resistant disease with clinical benefit or better response
Disease progression either clinically or radiographically after 1-2 previous regimens.
Disease-free of other malignancies
Widespread progressive disease, i.e., more than 3 sites of progressive disease (more than 3 sites of disease are permitted provided there are no more than 3 sites of progressive disease)
Leptomeningeal disease
Disease must be encompassed in a reasonable SBRT “portal” as defined by the treating radiation oncologist
Subjects with recurrent disease
Inclusion Criteria Include:\n\n          -  Patient has histologically- or cytologically- confirmed metastatic or advanced-stage\n             solid malignant tumor that is refractory to standard therapy and for whom no therapy\n             exists that would be curative or might provide significant benefit and therefore for\n             whom experimental therapy is a reasonable option.\n\n          -  Patient experienced progressive disease during or following or was intolerant of their\n             most recent treatment regimen.\n\n          -  Patient is male or female aged ?18 years.\n\n          -  Patient has an ECOG performance status of 0 (fully active, able to carry out all\n             pre-disease activities without restriction) or 1 (unable to perform physically\n             strenuous activity but ambulatory and able to carry out work of a light or sedentary\n             nature), as assessed on C1D1, before the first dose of TVB 2640.\n\n          -  Patient has adequate renal function (creatinine ?1.5 times the upper limit of normal\n             [ULN]) or a glomerular filtration rate (GFR) of ?50 mL/min.\n\n          -  Patient has adequate hepatic function,\n\n          -  Patient has adequate bone marrow function\n\n          -  Patient has no significant ischemic heart disease or myocardial infarction (MI) within\n             6 months before the first dose of TVB 2640 and currently has adequate cardiac function\n\n        For the Monotherapy Expansion Cohorts of the Study ONLY:\n\n          -  Patient has a specific tumor-type and histology, as designated by the Sponsor based on\n             nonclinical and clinical data obtained prior to enrollment in the Expansion Cohort.\n\n          -  Patient has measurable disease, as determined by the Investigator using RECIST,\n             version 1.1 (1).\n\n        For the Combination Cohorts ONLY:\n\n          -  In addition to meeting monotherapy criteria above, the commercially-available\n             anticancer agent of interest being investigated in combination with TVB-2640,\n             administered according to the dose regimen in the prescribing information, is deemed\n             appropriate for the patient's disease and clinical status.\n\n        Exclusion Criteria Include:\n\n          -  Patient is unable to swallow oral medications or has impairment of GI function or GI\n             disease that may significantly alter drug absorption\n\n          -  Patient has uncontrolled or severe intercurrent medical condition (including\n             uncontrolled brain metastases).\n\n          -  Patient underwent major surgery within 4 weeks before the first dose of TVB 2640 or\n             received cancer-directed therapy or an investigational drug or device within 4 weeks\n             (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is\n             shorter) before the first dose of TVB 2640.\n\n          -  If female, patient is pregnant or breast-feeding.\n\n          -  Patient has evidence of a serious active infection\n\n          -  Patient has a history of other malignancy treated with curative intent within the\n             previous 5 years with the exception of adequately treated non-melanoma skin cancer or\n             carcinoma in situ of the cervix.
General eligibility criteria:\n\n          -  ECOG performance status 0 or 1.Patients with multiple myeloma who have an ECOG\n             performance status of 2 based on peripheral neuropathy from prior therapies are\n             eligible.\n\n          -  Ability to understand and the willingness to sign a written informed consent document.\n\n          -  Pathological confirmation of AML, MDS-RAEB or Multiple myeloma.\n\n          -  Agree to use adequate contraception prior to the study, for the duration of study\n             participation, and 4 months after completion of CM-CS1 CART-cell administration.\n\n          -  Ability to adhere with the study visit schedule and other protocol procedures.\n\n          -  Willingness to remain within a 50 mile radius of Brigham Women's Hospital during the\n             initial 10 days following CM-CS1 infusion\n\n        Disease specific eligibility criteria for patients with AML, MDS-RAEB:\n\n          -  Pathological confirmation of AML, MDS-RAEB according to WHO classification (CMML is\n             excluded) that is not in remission (defined as >5% blasts in bone marrow or peripheral\n             blood) and for which there are no reasonable standard treatment options.\n\n          -  No known or suspected CNS disease. A neurologic exam is required and signs or symptoms\n             suggestive of potential CNS disease require CNS imaging.\n\n          -  Disease status deemed not to require additional therapy for at least 4 weeks from\n             enrollment.\n\n          -  Life expectancy of greater than 4 weeks.\n\n          -  Participants must have satisfactory organ function as defined below:\n\n               1. Total bilirubin ?2.0 × institutional upper limit of normal (Except for subjects\n                  with known Gilbert's syndrome)\n\n               2. AST(SGOT)/ALT(SGPT) ?3 × institutional upper limit of normal\n\n               3. Creatinine ? 2.0 mg/dL\n\n        Disease specific eligibility criteria for patients with multiple myeloma:\n\n          -  Diagnosis of active multiple myeloma according to the International Myeloma Working\n             Group diagnostic criteria.\n\n          -  Relapsed or relapsed/refractory multiple myeloma with progressive disease\n\n          -  Presence of measurable disease as defined as one or more of the following:\n\n               1. Serum M-protein >0.5g/dl\n\n               2. Urine M-protein > 200mg/24hr\n\n               3. Serum FLC assay: involved FLC level > 10mg/dl with abnormal serum FLC ratio\n\n               4. Measurable plasmocytoma in non-secretory patients.\n\n          -  Previous treatment with both an immunomodulator and a proteosome inhibitor therapy\n\n          -  Life expectancy of greater than 12 weeks\n\n          -  No known or suspected CNS involvement. A neurologic exam is required and signs or\n             symptoms of potential CNS involvement require CNS imaging. Peripheral neuropathy is\n             acceptable.\n\n          -  Participants must have satisfactory organ and marrow function as defined below:\n\n               1. Absolute neutrophil count > 500/mcL. Screening ANC should be independent of G-CSF\n                  and GM-CSF support for at least 1 week and of pegylated G-CSF for at least 2\n                  weeks\n\n               2. Platelets >20,000/mcL. Subjects may receive platelet transfusions, if clinically\n                  indicated, in accordance with institutional guidelines.\n\n               3. Total bilirubin ?2.0 × institutional upper limit of normal. (Except patients with\n                  known Gilbert's syndrome)\n\n               4. AST(SGOT)/ALT(SGPT) ?3 × institutional upper limit of normal\n\n               5. Creatinine ? 2.0 mg/dL\n\n        Exclusion Criteria:\n\n          -  Participants who have received chemotherapy or radiotherapy within 3 weeks prior to\n             entering the study or those who have not recovered from adverse events due to agents\n             administered more than 3 weeks earlier.\n\n          -  Concurrent systemic steroid or other immunosuppressive therapy.\n\n          -  Participants who are concurrently receiving any other investigational agents, or have\n             received another investigational agent within 3 weeks before enrollment.\n\n          -  Participants who have received prior allogeneic stem cell transplantation, gene\n             therapy, or adoptive T-cell therapy.\n\n          -  Active infections necessitating use of treatment antibiotics/antivirals during the\n             screening period (prophylaxis is acceptable) or evidence of an active communicable\n             infectious disease.\n\n          -  Participants who underwent major surgery within 4 weeks before day 0 of planned CM-CS1\n             T-cell infusion (this does not include placement of vascular access device or tumor\n             biopsies).\n\n          -  Participants with any known history of primary immunodeficiency.\n\n          -  History of allergic reactions or hypersensitivity attributed to Human serum albumin or\n             Plasma-lyte A.\n\n          -  Uncontrolled intercurrent illness or serious uncontrolled medical disorder\n\n          -  Pregnancy or breastfeeding\n\n          -  Known HIV-positive participants are ineligible because the effect of transducing\n             HIV-infected lymphocytes with the chimeric NKG2D- transgene on the disease course is\n             unknown.\n\n          -  Clinically relevant active infection including active hepatitis B or C or any other\n             concurrent disease which in the judgment of the Investigator would make the subject\n             inappropriate for enrollment on this study.\n\n          -  Active autoimmune disease\n\n          -  History of a malignancy other than one of the malignancies in this study with\n             exception of the following circumstances:\n\n               1. Patients with a history of malignancy who have been adequately treated and have\n                  been disease-free for at least 2 years are not excluded.\n\n               2. Patients with adequately treated active non-invasive cancers (such as\n                  non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers) are\n                  not excluded.\n\n          -  Unwillingness to use an effective contraceptive method during the study and at least 4\n             months after administration of CM-CS1 T-cells unless subject is naturally infertile.
Disease that is considered by the investigator to be rapidly progressing or life threatening such as extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumour (subjects who are intended for urgent chemotherapy)
Must have unresectable metastatic disease, and have tumor(s) present that is (are) evaluable by the RECIST, v1.1; may have spinal-associated metastases but must have concluded dexamethasone therapy and be evaluated by the Investigator to have stable CNS disease.
Inclusion Criteria:\n\n          -  Must have histologically-confirmed diagnosis of cholangiocarcinoma Stage II, III, or\n             IV CCA (intra-hepatic, extra-hepatic and perihilar) that is not eligible for curative\n             resection, transplantation, or ablative therapies. Tumors of mixed histology are not\n             allowed.\n\n          -  Must have radiographically measurable disease in at least one site not previously\n             treated with radiation, chemoembolization, radioembolization, or other local ablative\n             procedures; a new area of tumor progression within or adjacent to a previously-treated\n             lesion, if clearly measurable by a Radiologist, is acceptable.\n\n          -  May have received prior radiation, chemoembolization, radioembolization, or other\n             local ablative therapies, or hepatic resection if completed ? 4 weeks prior to\n             registration AND if patient has recovered to ? grade 1 toxicity. NOTE: Measurable\n             disease (as required above) must still be present.\n\n          -  May have received prior radiation for bone or brain metastases if patient is now\n             asymptomatic and has completed all radiation and steroid therapy (if applicable) ? 2\n             weeks prior to registration.\n\n          -  Age ? 18 years.\n\n          -  Child-Pugh score of A or B with ? 7 points.\n\n          -  Eastern Cooperative Oncology Group performance status of 0-1.\n\n          -  Willing to provide archived tissue, if available, from a previous diagnostic biopsy.\n\n          -  Must be able to tolerate CT and/or MRI with contrast.\n\n          -  Adequate organ function obtained ? 2 weeks prior to registration:\n\n               -  Absolute Neutrophil Count ? 1500/mm³\n\n               -  Hemoglobin ?9.0 g/dL\n\n               -  Platelets ?100,000/mm³\n\n               -  Serum Creatinine ? 1.5x Upper Limit Normal (ULN)\n\n               -  Creatinine Clearance ? 50 mL/min\n\n               -  Albumin ? 2.8 g/dL\n\n               -  Total Bilirubin ? 1.5 mg/dL or ? 1.5x ULN\n\n               -  Aspartate Aminotransaminase (AST)/Alanine Aminotransaminase (ALT) ? 2.5x ULN (?\n                  5x ULN in patients with liver metastases)\n\n               -  International Normalized Ratio (INR) <1.5x the ULN [INR ? 1.5 is allowed if\n                  anticoagulation is used.]\n\n          -  Women must not be pregnant or breastfeeding since nab-paclitaxel and/or gemcitabine\n             may harm the fetus or child.\n\n          -  Must not have received prior systemic cytotoxic chemotherapy or targeted therapy for\n             this cancer.\n\n          -  Must not be receiving treatment with other investigational agents.\n\n          -  Must not have a pre-existing >grade 2 peripheral neuropathy.\n\n          -  Must not be receiving immunosuppressive medications, including systemic\n             corticosteroids, aside from the following exceptions: used for adrenal replacement,\n             appetite stimulation, therapy for asthma, bronchitis exacerbation (? 2 weeks),\n             anti-emesis, or pre-medication for procedures (i.e. CT scan).\n\n          -  No known Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)\n             seropositivity.\n\n          -  Must not have undergone liver transplantation.\n\n          -  Must not have serious non-healing wound, ulcer, bone fracture, or abscess.\n\n          -  Must not have undergone a major surgical procedure <4 weeks prior to registration.\n\n          -  Must not have possible histories of pneumonitis or pneumonitis risk factors.\n\n          -  Must not have an active second malignancy other than non-melanoma skin cancer or\n             cervical carcinoma in situ.\n\n          -  Must have no ongoing or active, uncontrolled infections.\n\n          -  Must have no evidence of significant, uncontrolled concomitant diseases including, but\n             not limited to: symptomatic congestive heart failure, unstable angina pectoris,\n             uncontrolled cardiac arrhythmia, myocardial infarction within preceding 12 months,\n             uncontrolled peripheral vascular disease, cerebrovascular accident within preceding 12\n             months, pulmonary disease impairing functional status or requiring oxygen, connective\n             tissue disease including lupus.\n\n          -  Must not have any history of allergic reaction(s) attributed to compounds of similar\n             composition to nab-paclitaxel or gemcitabine.
Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not be candidates for therapy of proven efficacy for their disease
History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding within 6 months prior to Day 1 of Cycle 1
Prior to registration, patients must have achieved clinical benefit with crizotinib monotherapy and subsequently have systemically progressed; clinical benefit is defined as having stable disease on crizotinib monotherapy for at least 90 days or achieving a confirmed partial or complete response; systemic progression is defined as progressive disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, excluding progression based on brain/CNS metastases alone
Subjects who have clinical evidence of carcinoid-induced heart disease
Cardiomyopathy or history of ischemic heart disease. o Participants with ischemic heart disease who have had acute coronary syndrome (ACS), myocardial infarction (MI), or revascularization (example, coronary artery bypass graft, stent) in the past 6 months are excluded. However, participants with ischemic heart disease who have had ACS, MI, or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.
Any of the following within 3 months prior to study entry: grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event
Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria, and have relapsed or become refractory to conventional therapy
Patients with bilateral disease
Clinical or neuroimaging evidence of extraocular disease or orbital optic nerve involvement
Disease refractory to a carfilzomib-containing regimen and/or a pomalidomide containing regimen. Refractory is defined as either failure to achieve a minimal response (MR) or better while on therapy, or development of progressive disease (PD) while on therapy or within 60 days from last dose of therapy.
Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be performed:
Progressed (> 25% increase in evaluable disease) or non-response on Revlimid or within 60 days of stopping Revlimid
Leptomeningeal disease as a manifestation of cancer
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Underlying renal disease with a high risk of disease recurrence in the transplanted kidney, including:\r\n* Focal segmental glomerulosclerosis (FSGS)\r\n* Type I or II membranoproliferative glomerulonephritis\r\n* Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura
Key Inclusion Criteria:\n\n        Male or female age ? 18 years with histologically confirmed diagnosis of melanoma and\n        unresected stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c regardless of prior line of therapy.\n        Subject is candidate for intralesional therapy administration into cutaneous, subcutaneous,\n        or nodal disease and must also have measurable disease, serum lactate dehydrogenase ? 1.5 x\n        upper limit of normal, and Eastern Cooperative Oncology Group (ECOG) performance status of\n        0 or 1, and adequate hematologic, hepatic, and renal organ function.\n\n        Key Exclusion Criteria:\n\n        Subject must not have clinically active cerebral metastases, greater than 3 visceral\n        metastases (this does not include lung metastases or any nodal metastases associated with\n        visceral organs) or any bone metastases melanoma, primary ocular or mucosal melanoma,\n        history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis,\n        or symptomatic autoimmune disease, or evidence of immunosuppression for any reason. Subject\n        known to have acute or chronic active hepatitis B or hepatitis C infection, or human\n        immunodeficiency virus infection will also be excluded. Subject who has active herpetic\n        skin lesions or prior complications of herpes simplex virus type 1 ( HSV-1) infection (eg,\n        herpetic keratitis or encephalitis), and/or requires intermittent or chronic systemic\n        (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than\n        intermittent topical use will also be excuded. Subject must not have received previous\n        treatment with talimogene laherparepvec.
Rapidly progressing disease
Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis
Isolated extramedullary disease
Patients may be on specific targeted therapy (erlotinib or crizotinib) as long as they have not had disease progression
Does the subject have any gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine?
Patients must have measurable disease as defined by immune-related complete response (irRC) (Wolchok, 2009); all sites must be evaluated within 4 weeks prior to beginning therapy
Patients with Hodgkin’s lymphoma with one or more of the following: \r\n* Less than complete response to first-line chemotherapy\r\n* Relapse within 12 months of completion of first-line chemotherapy\r\n* Relapse within a prior irradiation field\r\n* Less than complete metabolic response to second-line chemotherapy\r\n* Second relapse or beyond\r\n* Extranodal disease at the time of relapse\r\n* Presence of B symptoms at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease\r\n* Bulky disease (defined as any lesion greater than 5 cm) at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease
experienced no progression of disease per the irRC1
Patients enrolling in the retreatment cohort may have experienced localized disease progression that was treated with definitive therapy to return the patient to a state of stable disease. Examples include localized disease progression treated with complete surgical resection, a solitary brain metastasis treated with complete surgical resection or curative intent stereotactic radiosurgery, or a solitary bone metastasis that is treated with curative-dose radiation therapy.
Presence of leptomeningeal disease or dural metastases.
Leptomeningeal disease as a manifestation of cancer
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Leptomeningeal disease
Patients will be eligible following any type of allogeneic transplant if they have CMV, adenovirus or EBV infection persistent to standard therapy (as defined below):\r\n* Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or single or double umbilical cord blood\r\n* CMV, adenovirus or EBV infection persistent despite standard therapy\r\n** For CMV infection:\r\n*** Patients with CMV disease defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates OR\r\n*** Failure of antiviral therapy defined as the continued presence of pp65 antigenemia (> 1+ cell/100,000 cells) or deoxyribonucleic acid (DNA)emia (as defined by reference lab performing polymerase chain reaction [PCR] assay but usually > 400 copies/ml) after at least 7 days of antiviral therapy OR\r\n*** Relapse after antiviral therapy defined as recurrence of either pp65 antigenemia or DNAemia after at least 2 weeks of antiviral therapy\r\n** For CMV infection, standard therapy is defined as 7 days therapy with ganciclovir, foscarnet or cidofovir for patients with disease or recurrence after 14 days therapy\r\n** For EBV infection:\r\n*** EBV infection is defined as biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR OR clinical or imaging findings consistent with EBV lymphoma and elevated EBV viral load in peripheral blood\r\n*** For EBV infection, standard therapy is defined as rituximab given at 375 mg/m^2 in patients for 1-4 doses with a CD20 positive (+) tumor\r\n*** Failure is defined as there was an increase of less than 50% response at sites of disease for EBV lymphoma OR there was a rise or a fall of less than 50% in EBV viral load in peripheral blood or any site of disease\r\n** For adenovirus infection or disease:\r\n*** Adenovirus infection is defined as the presence of adenoviral positivity as detected by PCR, DAA or culture from ONE site such as stool or blood or urine or nasopharynx OR adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from two or more sites such as stool or blood or urine or nasopharynx\r\n*** Standard therapy is defined as 7 days therapy with cidofovir (if renal function permits this agent to be given)\r\n*** Failure is defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR or any other quantitative assay
No primary induction failure, defined as failure to achieve CR with first-line chemotherapy or chemoradiation, disease progression during first-line chemotherapy or chemoradiation, or progression or biopsy-proven disease persistence within 8 weeks of first-line therapy completion
Patients must have received at least one prior anticancer regimen for metastatic disease unless there is no other therapy available and evidence of progressive disease on study entry. Patients with stable disease will be included if there has been failure to respond to another drug(s) within the previous 3 months
Patients are also considered to have progressive disease when:\r\n* New bone or soft tissue lesions (eg, plasmacytomas) are identified; or\r\n* There is an unequivocal increase in the size of previously existing lesions; or\r\n* The development of an otherwise unexplained serum calcium > 11.5 mg/dL is also a marker of progressive disease (PD)
Patients with cutaneous disease only are not eligible
Progressive disease while receiving hormonal therapy or after surgical castration documented by at least one of the following: (1) increase in measurable disease per RECIST 1.1; (2) appearance of new lesions on bone scan consistent with progressive prostate cancer (>= 2 new lesions on bone scans if this is the only measure of progressive disease (PD); (3) rising PSA defined as 2 sequential increases above a previous lowest reference value; each value must be obtained at least 1 week apart
Subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis
Subject has a significant history of cardiovascular disease (e.g., myocardial infarction [MI], thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study
Patients must have measureable or evaluable disease
Subjects that have had more than one disease recurrence
Patients must have clonal disease measureable by serum free light chain (FreeliteTM) assay:
Any concomitant disease or condition which would interfere with the subjects' proper completion of the protocol assignment.
Patients with paraspinal extension of disease with visceral involvement
Patients must have evidence of progression of disease during or after last treatment
Patients with thyroid disease should be excluded unless their T4 is normal or they are on replacement therapy
Patient must have documented progressive disease within 3 months of his/her most recent cycle of chemotherapy
Inclusion Criteria:\n\n          1. Lymphoid malignancy that has relapsed or is refractory after two or more treatments\n             that are FDA approved or are commonly used clinically.\n\n          2. Subjects must have progressive disease requiring therapy. Subjects who are candidates\n             for observation only are not eligible.\n\n          3. Subjects are either not currently considered to be candidates or refuse potentially\n             curative therapies including peripheral stem cell or bone marrow transplant\n\n          4. Subjects must have measurable disease as per disease specific criteria\n\n          5. Must have received their last chemotherapy, biologic, radiotherapy, or investigational\n             therapy at least 4 weeks prior to enrollment; 12 weeks from their last\n             radioimmunotherapy; 3 months if the last therapy was bone marrow/ peripheral stem cell\n             transplant.\n\n          6. Age >18 years\n\n          7. ECOG performance status <2\n\n          8. Normal Ejection Fraction on ECHO scan\n\n          9. Subjects must have normal organ and marrow function as defined below:\n\n             Absolute neutrophil count >1000/mL Platelets >75,000/mL For subjects with known marrow\n             infiltration, ANC ?500 and platelets ?30,000 Total bilirubin <1.5 X institutional\n             upper limit of normal (ULN) (<2X ULN for subjects with Gilbert's syndrome) AST (SGOT)\n             and ALT (SGPT) <3 X institutional ULN (for subjects with hepatic involvement <5 X\n             institutional ULN) PT/INR and aPTT within 1.5 X institutional ULN Creatinine <1.5 X\n             institutional ULN OR Creatinine clearance >60 mL/min/1.73 m2 for subjects with\n             creatinine levels above institutional normal\n\n         10. Women of childbearing potential must have had a prior hysterectomy or have a negative\n             serum pregnancy test and be using adequate contraception prior to study entry and must\n             agree to use adequate contraception from study entry through at least 6 months after\n             discontinuation of study drug. Men must also agree to use adequate contraception\n             (hormonal or barrier method of birth control; abstinence) prior to study entry and\n             from study entry through at least 6 months after discontinuation of study drug. Should\n             a woman enrolled in the study or a female partner of a man enrolled in the study\n             become pregnant or suspect she is pregnant while participating in this study or within\n             6 months after discontinuation of study, she should inform the Investigator\n             immediately.\n\n         11. Ability to understand and the willingness to sign a written informed consent document\n\n        Exclusion Criteria:\n\n        Subjects who meet any of the following criteria will not be eligible for participation in\n        the study:\n\n          1. Currently receiving any therapeutic treatment for lymphoid malignancies including\n             other investigational agents\n\n          2. Prior treatment with gamma secretase inhibitors or other Notch 1 inhibitors\n\n          3. Active CNS involvement, uncontrolled seizure disorder, or active neurologic disease\n\n          4. History of a Grade 4 allergic reaction attributed to humanized or human monoclonal\n             antibody therapy\n\n          5. Significant intercurrent illness including, but not limited to, ongoing or active\n             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac\n             arrhythmia, or psychiatric illness/social situations that would limit compliance with\n             study requirements\n\n          6. Pregnant women or nursing women\n\n          7. Ongoing malignancies or malignancies in remission <3 years other than the lymphoid\n             malignancies included in this trial. Patients with history of known skin cancers\n             including non-melanotic skin cancers within the past 3 years will not be included in\n             this trial. The following prior malignancies are allowable irrespective of when they\n             occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, and low-grade\n             local bladder cancer.\n\n          8. Subjects with known HIV infection\n\n          9. Known bleeding disorder or coagulopathy\n\n         10. Subjects receiving heparin, warfarin, or other similar anticoagulants, except for\n             subjects on low molecular weight heparin for DVT/PE prophylaxis. Note: Subjects may be\n             receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.\n\n         11. New York Heart Association Classification II, III, or IV\n\n         12. Subjects with a blood pressure of >140/90 mmHg that is not responsive to medical\n             therapy. Subjects taking antihypertensive medications must be taking ?2 medications to\n             obtain this level of blood pressure control.\n\n         13. Subjects with EKG evidence of ischemia or ?Grade 2 ventricular arrhythmia, subjects\n             who have a history of acute myocardial infarction within 6 months, or subjects with\n             unstable angina.\n\n         14. Subjects with known clinically significant gastrointestinal disease including, but not\n             limited to, inflammatory bowel disease\n\n         15. Subjects with diarrhea at time of enrollment or have an ongoing requirement for anti\n             diarrheal therapy
Progressive disease or marked splenomegaly and/or lymphadenopathy.
Patients must have relapsed or refractory disease after ?1 prior line of treatment.
Refractory disease on most recent therapy, or disease recurrence following remission on most recent therapy;
Active heart disease
No active peptic ulcer disease
Prior radioactive iodine must have been completed at least 6 months prior to registration, or there must be documented disease progression since such therapy if it was within 6 months; sites that have received EBRT must have disease progression post-EBRT to be used as sites of measurable disease
Patient has relapsed or relapsed/refractory multiple myeloma (MM)\r\n* Relapsed is defined as the development of disease progression following the achievement of stable disease (SD) or better to the most recent anti-MM regimen\r\n* Refractory is defined as experiencing less than a partial response (PR) to or progressive disease (PD) within 6 months after completion of the most recent anti-MM regimen
Patients must have reached Week 24 of the core protocol in immune-related complete response (irCR), immune-related partial response (irPR), immune-related stable disease (irSD), or immune-related progressive disease (irPD) (unconfirmed) with evidence of tumor inflammatory reaction.
Patients must have at least ONE of the following: Recurrent/progressive disease at any time prior to study enrollment - regardless of response to frontline therapy. Refractory disease: persistent sites of disease after achieving a best overall response of no response to front line therapy after a minimum of 4 cycles of induction therapy AND patient has never had recurrent/progressive disease. Persistent disease: persistent sites of disease after achieving a best overall response of partial response to frontline therapy after a minimum of 4 cycles of induction therapy AND patient has never had recurrent/progressive disease.
For recurrent/progressive or refractory disease, a biopsy is not required regardless of number of MIBG avid lesions
Presence of active nodal metastases (e.g., radiologic or clinical evidence of current nodal disease)
Has progressive disease at time of enrollment defined as one or more of the following criteria: PSA progression defined by PCWG2 criteria or soft tissue disease progression defined by RECIST 1.1 or bone disease progression defined by PCWG2 criteria Able to swallow and retain orally administered medication.
Disease must be considered unresectable at the time of preoperative evaluation
Recurrent disease, refractory disease, or progressive disease after having received at least one standard therapy for their disease. Note: Subjects with metastatic (and surgically unresectable) melanoma can be enrolled for first-line treatment; Melanoma subjects with CNS involvement may be enrolled.
Patients with newly diagnosed, unresectable, metastatic, and measurable ASPS who show clinical evidence of disease progression (including history and increasing physical symptoms) will also be eligible; on-study documentation will include a physician’s rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain)
Patients who have a diagnosis of Gilbert's disease
Patients with pT3 or pT4 disease
Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.) which would preclude RT
Relapsed/refractory, pathologically confirmed EBV+ lymphoid malignancy or lymphoproliferative disease
Underlying primary disease, for which the subject underwent transplant, is in morphologic remission
Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control which may require combination chemotherapy)
Leptomeningeal disease
Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy occurring within 6 months of study entry, as evidenced by: at least a 20% increase in radiographically or clinically measurable disease, appearance of any new lesions, or deterioration in clinical status
Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.
All patients must have evidence of progressive disease on study entry.Previously untreated patients who are not chemotherapy candidates on Arm 2 may have advanced disease (without clear progression). There is no upper limit on the number of prior treatments provided that all inclusion criteria are met and exclusion criteria are not met.
Patient has evidence of progressive disease while receiving iniparib.
Patient is receiving concurrent radiation therapy to treat primary disease with curative intent. (Note that palliative radiotherapy is allowed as long as there is no evidence of progressive disease.)
Patients must have measurable disease in two dimensions and >= 2 cm is acceptable (or 1.5 cm if 0.5 slices are used, as in spiral computed tomography [CT] scans); lesions that are considered intrinsically non-measurable include the following:\r\n* Bone lesions\r\n* Leptomeningeal disease\r\n* Ascites\r\n* Pleural/pericardial effusion\r\n* Inflammatory breast disease\r\n* Lymphangitis cutis/pulmonis\r\n* Abdominal masses that are not confirmed and followed by imaging techniques\r\n* Cystic lesions\r\n* Lesions that are situated in a previously irradiated area
Isolated extramedullary disease
Must have metastatic, progressive, castrate-resistant prostate cancer (CRPC) with radiographic evidence of disease that has continued to progress radiographically or biochemically (rising prostate-specific antigen [PSA] levels on successive measurements) despite adequate androgen-deprivation therapy; if patients had been on flutamide, disease progression is documented 4 weeks or more after withdrawal; for patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal; flutamide, nilutamide and bicalutamide disease progression requirements only apply to patients who have been on these drugs for at least the prior 6 months
Participants may not be receiving any other study agents or other types of cancer therapy while on this protocol except for disease progression
Active disease and indication for treatment based on the IWCLL updated NCI-WG guidelines, defined by presence of at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development or worsening of anaemia and/or thrombocytopenia; Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly; Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy; Progressive lymphocytosis with an increase of more than 50% over a two-month period or a lymphocyte doubling time of less than 6 months.
History of NSCLC treated with surgery and/or radiotherapy previously and disease has been cured or clinically no disease progression for more than 6 months, now isolated recurrent disease in lung parenchyma and without involvement of main bronchus, chest wall, hilar/mediastinal lymph nodes and critical mediastinal structures; biopsy of recurrent disease is recommended
Patients may have had prior chemotherapy or immunotherapy (vaccines, interferon, ipilimumab, or IL-2) with progression or persistent disease
Prior chemoembolization, radioembolization, radiofrequency ablation (RFA) or other local ablative therapies are permissible if >= 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable
Evidence of leptomeningeal spread of disease.
Relapsed disease after standard 1st line therapy for aggressive lymphoma - not eligible for high dose chemotherapy with stem cell support. Relapsed or refractory disease after two lines of therapy one of which could have included Autologous Stem Cell Transplant (ASCT). Relapsed disease is defined as progression after a disease free interval of at least 6 months after completion of last therapy. Refractory is defined as progression of disease during prior therapy or within 6 months from its completion.
Target Disease Exceptions
Radiographic evidence of disease
Subjects must have documented disease progression prior to enrolling into the study
Part II: Postmenopausal women with locally ABC or MBC whose disease has progressed during or after treatment with an AI. Participants who discontinued the AI for toxicity rather than completion of regimen or for disease progression are not eligible
Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable)
Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable)
Subjects with recurrent ovarian, fallopian tube or peritoneal cancer who have clinical or radiologic evidence of a complete or partial response or stable disease after completion of first-line chemotherapy for their recurrent disease and are not suitable for additional cytotoxic therapy are eligible. These subjects may have previously received a course of adjuvant chemotherapy earlier in their disease management as described in point one above. These subjects are eligible regardless of their CA-125 results. These subjects may have been in a clinical trial of an investigational therapy.
Non or minimally daily activities-interfering disease related symptoms.
Has multicentric Castleman's disease
Unmanageable toxicity, an adverse event, progression of disease, or withdrawal of consent as reason for discontinuing treatment from previous sponsor-initiated siltuximab study
Randomization within 4 weeks of progression of disease
Relapsed, refractory, or progressive Hodgkin’s lymphoma meeting one of the following criteria, and autologous BMT is not recommend:\r\n* PR or better prior to transplantation\r\n* Stable disease prior to transplantation, provided that the disease is low-volume and disease control is regarded as sufficient to proceed with BMT; eligibility of such patients will be determined on a case-by-case basis with the principal investigator (PI) or co-PI
Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)
Radiographic evidence of disease progression by RECIST criteria on or after the last anti-cancer therapy within the 6 months prior to randomization.
Lesions that have had radiotherapy must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
Any serious concomitant illness or infectious disease requiring treatment, or infectious disease not requiring treatment, but with significant risks for myelosuppressive complications associated with chemotherapy.
Refractory is defined as experiencing less than minimal response (MR) to or progressive disease (PD) within 60 days after completion of the most recent anti-MM regimen
Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
Patients must have disease that is not amenable to potentially curative resection or ablative techniques; in addition, disease must not be amenable to or have progressed on transhepatic arterial chemoembolization (TACE); patients must not be considered potential candidates for liver transplantation; this determination will be made after hepatobiliary surgical input at the NCI multidisciplinary conference
History of peptic ulcer disease or hemorrhagic gastritis within 6 months of TRC105 administration, unless patient has received adequate treatment for peptic ulcer disease or hemorrhagic gastritis and has evidence of complete resolution documented by esophagogastroduodenoscopy (EGD); mild gastritis is allowed
Part A: Have the presence of measurable or nonmeasurable disease as defined by the RECIST v1.1 (Eisenhauer et al. 2009) or Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) or have measureable disease for multiple myeloma.
Evidence of disease progression, as determined by the investigator
Known gallbladder or bile duct disease, acute or chronic pancreatitis
c. carfilzomib. Demonstrated disease progression on or within 60d of completion of carfilzomib therapy
Patients with recurrent T1 disease who do not wish to have cystectomy.
Documented relapse or progressive disease on or after any regimen
Alcoholism or hepatic disease.
Patients with impending death from another disease.
Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis)
For subjects who are deemed to be eligible for high-dose interleukin-2 (IL-2) and elect to receive this therapy, such subjects must have progressive disease post-IL-2 to enter this study; such subjects must also have received and have had progressive disease after therapy with one of the agents listed
Recurrent disease:\r\n* Patient > 5 years old (yo) must have recovered CD4 count to > 350 cells/mm3 OR have disease free interval > one year from completion of cytotoxic therapy\r\n* Patients < 5yo must have recovered CD4 count to > 360 cells/mm3 OR have disease free interval > six months from completion of cytotoxic therapy
Multiple recurrences are allowable as long as CD4 count or disease-free intervals have been met
Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the participant at undue risk to undergo treatment
Patients with known primary or metastatic CNS disease (cohort B), are not eligible if they have a mini mental state exam score < 15 or evidence of leptomeningeal disease
Known cerebral/meningeal disease.
Subjects with ulcerative chest wall disease defined as non-healing wounds consistent with cancer are eligible.
Symptomatic coronary artery disease
Known structural heart disease.
Stereotactic radiosurgery (SRS):\r\n* Patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease\r\n* At least 12 weeks between completion of SRS and initiation of bendamustine
Interstitial brachytherapy: patients must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium SPECT, MR spectroscopy and MR perfusion or surgical documentation of disease
Patients must have evaluable disease
Paget's disease.
Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior treatment.
Non-malignant disease that would render the patient unsuitable for treatment according to the protocol.
Has a suspected mechanical gastrointestinal obstruction, fecal impaction, or clinically important active diverticular disease as determined by the investigator.
Preexisting cardiovascular disease. The only exception being well controlled essential hypertension with a sitting blood pressure (B.P.) of < 160 systolic and < 90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of any of the following conditions is considered as exclusions to study participation:
Metastases in the brain or active epidural disease. (Note: patients with treated epidural disease are allowed);
Gross total resection followed by conventional chemoradiation therapy without progression of disease.
Presence of diffuse leptomeningeal disease or gliomatosis cerebri.
DISEASE CHARACTERISTICS:\n\n          -  Histologically confirmed metastatic melanoma, meeting any of the following criteria:\n\n               -  Progressive disease after chemotherapy, radiotherapy, surgery, or immunotherapy\n\n               -  No longer responding to standard therapy OR have refused standard therapy\n\n          -  Unresectable disease\n\n          -  Measurable or evaluable disease\n\n          -  No clinical ascites\n\n          -  No symptomatic pleural effusion\n\n        PATIENT CHARACTERISTICS:\n\n          -  Life expectancy ? 12 weeks\n\n          -  Karnofsky performance status 70-100%\n\n          -  Bilirubin ? 3.0 mg/dL\n\n          -  Albumin ? 3.0 g/dL\n\n          -  Alkaline phosphatase < 5 times upper limit of normal (ULN)\n\n          -  Serum glucose > 60 mg/dL\n\n          -  Amylase < 1.5 times ULN\n\n          -  Absolute neutrophil count > 1,500/mm³\n\n          -  Platelet count > 100,000/mm³\n\n          -  No New York Heart Association class III-IV heart failure\n\n          -  No serious infection requiring treatment with antibiotics\n\n          -  No known allergy to E. coli drug products (e.g., sargramostim [GM-CSF])\n\n          -  Not pregnant or nursing\n\n          -  Negative pregnancy test\n\n          -  Fertile patients must use 2 forms of effective contraception\n\n        PRIOR CONCURRENT THERAPY:\n\n          -  See Disease Characteristics\n\n          -  At least 4 weeks since prior anticancer therapy\n\n          -  At least 4 weeks since prior surgery and recovered\n\n          -  No concurrent participation in another investigational drug study
DISEASE CHARACTERISTICS:\n\n          -  Histologically confirmed colorectal cancer\n\n          -  Stage IV disease (i.e., any T, any N, M1 disease)\n\n          -  Relapsed or refractory disease\n\n               -  Disease progressed after ? 2 different fluorouracil-containing chemotherapy\n                  regimens (e.g., irinotecan hydrochloride or oxaliplatin with or without\n                  bevacizumab)\n\n          -  Bidimensionally measurable disease\n\n          -  Must have tumor amenable to biopsy and be willing to undergo fine-needle aspiration\n\n          -  No CNS metastases\n\n        PATIENT CHARACTERISTICS:\n\n          -  ECOG performance status 0-2\n\n          -  Life expectancy > 2 months\n\n          -  Platelet count > 100,000/mm^3\n\n          -  WBC ? 3,000/mm^3\n\n          -  Creatinine ? 1.5 times upper limit of normal\n\n          -  Bilirubin ? 2 times normal\n\n          -  SGOT ? 5 times normal\n\n          -  Not pregnant or nursing\n\n          -  Negative pregnancy test\n\n          -  Fertile patients must use effective contraception during and for at least 4 months\n             after completion of study treatment\n\n          -  No preexisting peripheral neuropathy ? grade 2\n\n          -  Ejection fraction ? 30%\n\n          -  Baseline QT interval < 500 msec\n\n          -  No serious underlying medical illness or active infection\n\n          -  No underlying medical condition that could be aggravated by the treatment\n\n          -  No life-threatening disease unrelated to colorectal cancer\n\n          -  No other malignancy within the past 5 years unless currently disease-free and all\n             therapy for the malignancy has been completed\n\n          -  No preexisting neurological disorder (i.e., seizure disorder) ? grade 3\n\n          -  No cardiac disease, including any of the following:\n\n               -  Recurrent supraventricular arrhythmia\n\n               -  Any type of sustained ventricular arrhythmia or conduction block (e.g., grade II\n                  or III atrioventricular block or left bundle branch block)\n\n               -  Uncontrolled ischemic heart disease\n\n               -  History of nonsustained ventricular tachycardia\n\n               -  Prolonged PR intervals (i.e., 1st degree heart block)\n\n          -  No known hypersensitivity to arsenic trioxide or fluorouracil\n\n          -  No history of allergic reactions attributed to compounds of similar biologic\n             composition to arsenic trioxide or fluorouracil\n\n        PRIOR CONCURRENT THERAPY:\n\n          -  See Disease Characteristics\n\n          -  Recovered from all treatment-related toxicity\n\n          -  At least 4 weeks since prior chemotherapy or radiotherapy and recovered\n\n          -  More than 4 weeks since prior investigational drug\n\n          -  No other concurrent investigational or commercial anticancer agent or therapy\n\n          -  Concurrent local radiotherapy allowed for symptom relief (e.g., significant onset of\n             pain after enrollment, but before beginning study therapy)
Patients should have any of the following disease status: a. responsive or stable disease on salvage chemotherapy or radiation therapy; b. untreated, smoldering (i.e. not rapidly progressive) relapses
Patients with documented disease progression on salvage chemotherapy
Prior to enrollment on ANBL0032, a determination of mandatory disease staging must be performed (tumor imaging studies including computed tomography [CT] or magnetic resonance imaging [MRI], MIBG scan, and vanillylmandelic acid [VMA]/homovanillic acid [HVA]; bone marrow aspirates are required but biopsy may be omitted if negative prior to ASCT); this disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before enrollment\r\n* For those with residual disease before radiotherapy, re-evaluation of irradiated residual tumors is preferably performed at the earliest 5 days after completing radiotherapy; patients with residual disease are eligible; biopsy is not required; patients who have biopsy proven residual disease after ASCT will be enrolled on Stratum 07\r\n* Patients must not have progressive disease at the time of study enrollment except for protocol specified bone marrow response and except for elevations of catecholamines as the only sign of disease in a patient who had normal catecholamines at pre-ASCT evaluation
Veno-occlusive disease, if present, should be stable or improving
Disease status\r\n* Tumors must have NOT been completely resected, or must be locoregionally recurrent if previously resected; tumor must be deemed potentially resectable by local surgeon\r\n* MM arising from the head/neck, genitourinary, or gastrointestinal tract\r\n* Disease meets any 1 of 4 characteristics:\r\n** Regional lymph node (LN) involvement; OR\r\n** Multifocal/satellite primary disease; OR\r\n** Single localized, primary disease meeting one of the following site-specific requirements:\r\n*** Head/neck – any primary lesion if sinonasal; pT4a or above for nasal or oral cavity\r\n*** Anorectal – any primary lesion\r\n*** Conjunctiva – any primary lesion T2 or T3 stage by American Joint Committee on Cancer (AJCC)\r\n*** Vaginal/cervical – any primary\r\n*** Vulvar (hair bearing surface, labia majora) – AJCC cutaneous stage IIB or higher\r\n*** Esophageal – any primary\r\n** Locoregionally recurrent following prior resection\r\n* No evidence of metastatic disease at the time of registration
Patient is either ineligible for or declines radical cystectomy; the investigator must explain that a delay in cystectomy may increase the patient’s chance of disease progression
Progressive disease after treatment with single-agent nivolumab
Patients must meet one of the following two requirements:\r\n* Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after receiving a minimum of two cycles\r\n* Have a partial response but show a decrease less than 25% or an increase less than 25% in measurable disease over a two month period\r\n** NOTE: Patients may be refractory to primary therapy or relapsed and have measurable or assessable disease; (refractory disease is defined as anything less than partial response [PR] or progression within 60 days of completing therapy)
Patients who have no measureable disease by serologic or urine markers (detectable disease only by bone marrow or imaging scans)
Patients who show progressive disease or are not tolerating the current chemotherapy regimen
Patients must have biopsy accessible disease and must be willing and able to undergo a biopsy
Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study drugs
Patients must have refractory disease, disease relapse or progression after at least two prior systemic chemotherapy or immunotherapy regimens\r\n* Note: Exceptions may be made if a patient is deemed unfit for first-line salvage therapy by the treating physician; such cases should be clearly documented
Patients with active disease outside the thorax may be eligible for study once the extrathoracic disease is definitively treated by local modalities such as radiation, surgery, or radiofrequency ablation
Patients with uncontrollable progression of extra-thoracic disease will be excluded from study
Women with stages II-IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who have completed standard therapy for primary or recurrent disease (i.e., patients who would normally be observed); eligible patients may have asymptomatic residual measurable disease on physical examination and/or computed tomography (CT) scan, and/or may have an elevated cancer antigen 125 (CA-125); or may be in complete clinical remission after treatment for primary or recurrent disease; these patients would normally enter a period of observation after standard management
Specimens for cytogenetic analysis are required, and must be obtained prior to therapy initiation; for patient with refractory disease, the diagnostic specimen may be used
Histological confirmation of urothelial carcinoma and high risk residual disease after neoadjuvant chemotherapy (NAC) and cystectomy as defined by post-operative pathological pT4 or N1-3 disease, or progressive disease during NAC (NAC include methotrexate, vinblastin, doxorubicin and cisplatin [MVAC], dose dense MVAC, gemcitabine cisplatin, or gemcitabine carboplatin); minor histologic variants (< 50%) are acceptable if urothelial carcinoma is predominant variant
For transplant-ineligible patients, salvage therapy just prior to MDV9300 treatment must have resulted in a PR or stable disease;
Serious active infectious disease
Objective evidence of disease progression on study entry
Any patient with active connective tissue disease such as lupus, dermatomyositis
Nodal disease as detected by clinical exam or CT
A known diagnosis of Wilson’s disease
Are unable to catheterize due to a urethral stricture disease,
No unstable neurologic, hepatic, renal, cardiovascular, lymphatic, or metabolic disease
Patient must be without clinical evidence of loco-regional and distant disease, as evaluated according to institutional assessment standards and documented in the patient record
Progressive cancer (must be considered no evidence of disease or stable)
Definitive evidence of multifocal disease
For stage I-III disease, patients should be 2-24 months post-completion of surgery, radiation therapy and/or chemotherapy with no further planned treatment during the 12-week study and no evidence of disease
For stage IV disease, patients may be receiving no treatment or may be receiving maintenance treatment with a target agent, chemotherapy, or immunotherapy provided the most recent imaging does not demonstrate progressive disease
Progressive cancer (must be considered no evidence of disease or stable)
Myasthenia gravis or other neuromuscular disease
Symptomatic nodal disease, i.e. scrotal, penile or leg edema
No evidence of disease
Cancer survivor, with no evidence of active disease
Patients with known diagnosis of a primary mast cell disease (ie. mastocytosis)
Hereditary metabolic bone disease or skeletal dysplasia (e.g., osteopetrosis or osteogenesis imperfecta [OI]) or primary hyperparathyroidism
Patient’s disease status should meet criteria as outlined by institutional master protocol
progression of disease at the time of Enrollment
Bulky disease (> 10 cm) at diagnosis or at relapse/refractory disease confirmation
Recurrent or persistent progressive disease which is refractory to curative therapy or established treatments and cannot be treated with surgery or radiotherapy;
Phase II: Participants must have a diagnosis of AML and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)\r\n* Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy\r\n* Patients are eligible at first or subsequent relapse or any relapse that is refractory to salvage chemotherapy
Has disease that is suitable for local therapy administered with curative intent
Participants with accessible disease must be willing to undergo a research biopsy before beginning crossover therapy
Patient is not currently on hemodialysis and/or peritoneal dialysis for management of chronic kidney disease or acute failure/conditions.
Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of subsequent progressive disease (substantial size increase of ?20%) to be deemed a target lesion.
Evidence of progressive disease as compared to pre-HCT (persistence of disease is permitted)
Active infectious disease considered by the Investigator to be incompatible with the protocol.
History of neurological disease (e.g., Parkinson’s Disease, dementia, mild cognitive impairment)
With diagnosis of malignant or benign disease
Have a diagnosis of psychiatric illness or other major illness in addition to PCa, such as other cancers, uncontrolled hypertension, lung disease, liver disease or heart disease
Previous or current neurologic disease affecting the lower hemithorax or below
Medical conditions felt to be clinically contributing to fatigue based on the investigator’s history, physical examination, and assessment: anemia (hemoglobin less than 10 g/dl), hypothyroidism (thyroid stimulating hormone greater than 4.6 MCU/mL), uncontrolled pain, medical problems associated with fatigue: chronic obstructive pulmonary disease, congestive heart failure, renal disease, hepatic dysfunction, autoimmune disease, neurological disorders such as multiple sclerosis or Parkinson’s disease, and poorly controlled sleep apnea
Neurologic, metabolic, or vascular diseases that may negatively impact erectile function, such as: diabetes mellitus, peripheral vascular disease, coronary artery disease, stroke, multiple sclerosis, Parkinson’s disease, multiple systems atrophy, epilepsy, or spinal cord injury.
The presence of known ischemic heart disease as defined by significant obstructive heart disease (stenosis > 70%) seen on coronary angiography or cardiac computed tomography (CT)
4D CT positive for multiple gland disease
Eligible patients must be considered disease-free or have stable disease
Participants who develop treatment complications or disease recurrence after being enrolled in the study may continue to participate if they are able to do so
Chronic diarrhea or malabsorptive diseases (e.g., Crohn’s disease)
Have no current evidence of disease
If participating in optional biospecimen collection; as per self-report, has medical conditions that affect the immune system and would confound immune evaluation (e.g., autoimmune disorder, inflammatory disease; uncontrolled thyroid disease; active infection; myocardial infarction or stroke in the last 6 months; type I diabetes; acute hepatitis; recent vaccination for viral disease)
Unstable psychiatric disease (psychotic disorders or major depression identified using Brief Psychiatry Rating Scale [unless stable in treatment for 3 months]) - smokers with stable psychiatric disease will be eligible
Current thromboembolic disease requiring full-dose anticoagulation patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
Will exclude patients with current, active peptic ulcer disease
Significant kidney disease that would inhibit administration of gabapentin
Patients with gross disease involving only the posterior elements
Receipt of an HSCT due to an oncological disease
Malignant pancreatic disease
Subjects with chronic kidney disease or concomitant parathyroid disease
Active extramedullary disease
Evidence of complete response at three months post-treatment; maintenance therapy is permitted as long as there is no evidence of disease
There is evidence of the disease at the time of entry into the trial
Skin disease in target irradiation area
No known evidence of disease
Current or previous neurological disease, which may adversely affect swallowing
Conditions that could affect participation in yoga such as spinal disease or unstable joints
Patients with relapsed disease post-HCT
Radiologic evidence of distant disease
Patients across all stages of disease
Asthma or other reactive airway disease
A probability of 60% or higher of a lung lesion being malignant as calculated by Bayesian analysis derived from clinical and radiographic criteria or, alternatively, biopsy proven disease
Any condition that would prevent the subject from performing the research procedures (e.g., unstable coronary artery disease)
Patient with a secondary malignancy who would be otherwise eligible for study, but for whom remission from the primary disease cannot be conclusively confirmed or for whom the chance of relapse of the primary disease is significant
No active gallbladder disease
Patients with no active disease; (as defined as no detectable disease)
Deemed disease free by the treating physician
Within 48 hours of receiving either metronidazole for mild-moderate disease or vancomycin for severe uncomplicated disease
Other known etiology of diarrhea (e.g. other enteric pathogen, other intestinal disease)
Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
Unstable medical problems (such as unstable heart disease, unstable hypertension, diabetes in poor control, respiratory disease complicated by hypoxia or hypercapnia, infectious illnesses, unstable thyroid dysfunction, currently hospitalized)
History of or current neurological illness that significantly impacts cognition (e.g. stroke, multiple sclerosis, Parkinson's disease, Alzheimer's disease, head injury, epilepsy, etc)
Evidence of active progression of disease or recurrence
Recurrent disease
Those receiving alternate regimens and those with other disease types
Participants who develop treatment complications or disease recurrence after being enrolled in the study may continue to participate if they are able to do so
Have no contra-indication to moderate to vigorous aerobic exercise (e.g., infection, cardiopulmonary disease, musculoskeletal disease, psychiatric condition)
PATIENT: Informed of diagnosis of incurable disease within the previous 8 weeks
Evidence of active malignant disease
Patients with local disease recurrence would be excluded from the trial
Presence of evaluable disease
Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening
Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression
For Part 1: Histologically- or cytologically-confirmed diagnosis of unresectable GIST or another advanced solid tumor. Patients with unresectable GIST must have disease that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an experimental kinase-inhibitor agent, or disease with a D842 mutation in the PDGFR? gene. Patients with an advanced solid tumor other than GIST must have relapsed or refractory disease without an available effective therapy. OR For Part 2:
Non-bulky disease defined as less than 10 cm in maximal diameter
Available for follow-up of their disease after treatment until progressive disease is documented and resolution of related adverse events until < grade 2
Systemic (extraperitoneal) disease, pregnant, incarcerated
Leptomeningeal disease
Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
Active malignant disease relapse
Patients who currently have no evidence of disease
Presence of extensive skeletal metastases defined as more than five (5) sites of bony disease, or any symptomatic site of disease in the spine, hip, or femur; Note that, patients with more than five bony sites may be deemed eligible at the discretion of the attending oncologist
Concurrent hepatic veno-occlusive disease (VOD)
Patient must have no evidence of progressive disease on restaging imaging within 3 months of enrollment
Patient must not have evidence of progressive disease
Patients must not have concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including: inflammatory arthritis (e.g., rheumatoid arthritis, systemic lupus, spondyloarthropathy, psoriatic arthritis, polymyalgia rheumatica), gout, episodes of acute monoarticular arthritis clinically consistent with pseudogout, Paget's disease affecting the study joint (knees/hands), a history of septic arthritis or avascular necrosis or intra-articular fracture of the study joint, Wilson's disease, hemochromatosis, alkaptonuria, or primary osteochondromatosis
Clinical (e.g. multiple cranial nerve deficits in the absence of obvious radiographic disease to explain symptoms) or radiographic evidence of leptomeningeal disease
Major psychiatric disease
Evidence of relapsed disease
Thalassemia major or sickle cell disease requiring blood transfusion
Chylous effusions associated with malignant disease
Active peptic ulcer disease or evidence of gastrointestinal bleed
Cardiovascular disease (unless the disease would not compromise the patient’s ability to participate in the exercise rehabilitation program)
If they have angina or unstable coronary disease
AML patients with persistent disease from the recent treatment defined as > 5% blast and/or > 20% cellularity and reported as persistent residual disease by a pathological report of the patient's bone marrow biopsy 14 days +/- 2 days from the initiation of cytarabine
No additional restrictions exist regarding co-morbid disease or incurrent illness
Be considered disease-free at baseline
Neurologic disorders of stroke, encephalitis, dementia, epilepsy, Alzheimer’s disease, Parkinson’s disease
Survival 1-2 years after most recent HCT with no evidence of relapse, disease progression, or secondary cancer on last follow-up
Active disease relapse
Medical conditions felt to be clinically contributing to fatigue based on the investigator’s history, physical examination, and assessment: anemia (hemoglobin less than 10 g/dl), hypothyroidism (thyroid stimulating hormone greater than 4.6 MCU/mL), uncontrolled pain, medical problems associated with fatigue: chronic obstructive pulmonary disease, congestive heart failure, renal disease, hepatic dysfunction, autoimmune disease, neurological disorders such as multiple sclerosis or Parkinson’s disease, and poorly controlled sleep apnea
Presence of muscle spasms or active neurologic disease prior to start of vismodegib
Presence of significant renal disease or hemodialysis which would result in dramatic reductions of systemic levocarnitine levels
Patients with clinical evidence of gross disease
Previous or current neurologic disease affecting the lower hemithorax or below
Evidence of disease progression that would necessitate a treatment in the next 2 weeks
Evidence of malignancy within 6 months of study enrollment; this is defined as clear morphologic, radiologic or molecular evidence of disease; mixed chimerism is allowed at the discretion of the clinician
Acute or chronic respiratory disease
Study participants are expected to be generally healthy and non-symptomatic for cervical disease
Patient must be asymptomatic for breast disease and undergoing routine screening
Current skin disease or fungal infection of the feet;
Previous medical history of gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, severe diverticulitis, heart failure (Class III or IV), serious cardiovascular disease, ulcerative colitis or Crohn's disease.
Men with human immunodeficiency virus (HIV) and/or prior anal disease will be included given their increased risk for current disease
Patients must have no other chronic disease that would preclude randomization into a lifestyle intervention trial; such diseases include recent myocardial infarction or unstable angina (in the previous 6 months), chronic hepatitis, rheumatoid disease, renal or hepatic disease/dysfunction and diabetics receiving insulin; or other clinical condition limiting ability to walk (recent leg fracture, significant osteoarthritis, related orthopedic conditions, degenerative neurological conditions, etc.)
Patients diagnosed with chronic disease/illness precluding their participation (i.e., diabetics receiving insulin, myocardial infarction or unstable angina within previous 6 months, chronic hepatitis, rheumatoid disease, renal or hepatic disease/dysfunction)
CONTROL (HEALTHY) GROUP: Healthy female without known coronary artery disease
CONTROL (HEALTHY) GROUP: Overt coronary artery disease or heart failure
Pulmonary disease, renal dysfunction, hepatic disease, cardiac disease, neurologic disease;
current known immunologically-deficient disease conditions (not including recent chemotherapy);
Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerisms is permitted)
FOR THE 31 SUBJECTS ENROLLED IN YEAR 1: Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerisms is permitted)
No evidence of residual disease on scan
Evidence of hematologic malignancy or disease relapse post-transplant (stable mixed chimerisms are permitted)
Documented evidence of fibrosis or cirrhosis (Metavir 2, 3, and 4) and subjects with significant extrahepatic manifestations of hepatitis C (such as cryoglobulinemia with symptoms or evidence of end-organ manifestations, renal disease, type 2 diabetes, or porphyria cutanea tarda
Prior cancers allowed if no evidence of disease
Active peptic ulcer disease
Participants must not have evidence of active/recurrent malignant disease for a minimum of 6 months.
Known heart disease
Evidence of progressive disease at the time of study enrollment
Known heart disease
Patients with active, progressive or advanced disease based on diagnosis
Driver currently has (or has a history of) any cardiovascular disease (CVD) including coronary artery disease, angina or aortic stenosis; this does not include hypertension
CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30 cells); NOTE: CD30 + disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard
Have an active metabolic or digestive illness that impact phytochemical absorption and metabolism, including: diabetes, malabsorptive disorders (Crohn’s disease, documented celiac disease, etc.), renal insufficiency (creatinine [Cr] > 1.4), hepatic insufficiency (nonalcoholic steatohepatitis [NASH], cirrhosis, active viral hepatitis), hyper- or hypothyroidism, or short bowel syndrome
Participants must not have evidence of active/recurrent malignant disease for 6 months
Individuals with active gastroduodenal ulcer disease in the preceding 5 years
Pancreatic insufficiency or disease
Known chronic kidney disease (creatinine >= 3.0)
Participants in the control group must be disease free, never-smokers and otherwise healthy
Patients with a known connective tissue disease
Disease Status: Neuroblastoma that is in remission
Disease Status: Neuroblastoma that is in remission
Have heart disease, lung disease, or mental illness
Documented disease progression or stable disease as best response to treatment (or attempted treatment) with azacitidine for injection or decitabine. Those achieving an objective response to treatment regimen with an injectable Hypomethylating agent (HMA) are excluded from participation in this study. Definitions of disease progression are modified from IWG (INTERNATIONAL WORKING GROUP) 2006 criteria and include:
Patients with immediately life-threatening visceral disease for whom chemotherapy is preferred treatment option.
Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
Current corneal disease or a history of corneal disease.
cN0 or cN1 disease
cNX, cN2, or cN3 disease
Disease Status: Refractory or first or multiple relapsed neuroblastoma, or medulloblastoma that has relapsed after, or is refractory to, a chemotherapy-containing treatment regimen.
Current disease state must be one for which there is currently no known curative therapy.
Evidence of disease progression or metastatic disease during or following definitive local therapy documented in the 10- to 12-week post-definitive local therapy scans
A radiological diagnosis of recurrent/relapsed or progressive disease according to RANO criteria.
Subject has MF with evidence of persistent disease despite ruxolitinib monotherapy treatment, consisting of:
History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
No evidence of disease (in situ or invasive cancer that would normally be treated by resection) at trial entry as determined by the investigator
Current metabolic or life-threatening disease
Diagnosis of kidney disease requiring dialysis
Dermatological disease within the acupuncture area
T2 disease
Patients in whom the lock solution application will interfere with routine treatment of the underlying disease
Serious medical condition (e.g., cancer, heart disease, kidney disease, diabetes)
Patients must be without evidence of residual disease as assessed by their treatment team
No evidence of disease
Acute disease and/or fever at the time of enrolment.
Other chronic disease unrelated to HSCT that may impact bone metabolism
Patients who have multicentric disease
No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies; multifocal disease that can be encompassed in a single operative bed can be enrolled; for patients with multifocal or multicentric disease enrolled after completion of neoadjuvant chemotherapy, histologic confirmation of multifocality/multicentricity must have been completed before initiation of chemotherapy
Patient must be cleared for bevacizumab administration with respect to any recent surgeries, and post-surgical scans must confirm the presence of measurable residual disease
Participants with a known Li-Fraumeni or Cowden’s disease
Patients who have biopsy confirmed multi-centric disease
Participants with known Li-Fraumeni or Cowden’s disease
Patients who have biopsy confirmed multi-centric disease
EXCLUSION - HEALTHY VOLUNTEERS: Known kidney disease
Patients with local or regional nodal disease are eligible
Known Paget’s disease
Patients must have evidence of disease either through elevation of tumor markers or radiologic evidence of disease
Good general health with no history of diabetes, coronary artery disease, peripheral arterial disease, chronic disease or hypertension
Castration-resistant disease according to PCWG2 criteria
Significant auto-immune disease requiring hospitalization within the past two years or any history of life-threatening auto-immune disease
Patient must have at least one area of disease measuring >= 1.0 cm
Have kidney disease, defined as either CKD II-V, determined by estimated glomerular filtration rate (GFR) of < 90 and derived from serum creatinine measurements, or albuminuria/proteinuria, determined by albumin to creatinine ratio or protein to creatinine ratio of > 30 mg/gm within 3 months of recruitment, or on dialysis or having received a kidney transplant or have biopsy proven kidney disease
CRITERIA FOR HEALTHY VOLUNTEERS: Subject meets all criteria above but does not have a clinical diagnosis of respiratory disease
Patients with ongoing febrile illness or documented infectious disease
PHASE I: All patients must have MIBG-avid disease and evaluable disease on MIBG scan at the time of enrollment onto the protocol
EXPANSION COHORT: Patients must have MIBG-avid disease and evaluable disease on MIBG scan at the time of enrollment onto the protocol
Patients with the diagnosis of neuroblastoma must meet both of the following criteria: \r\n* Diagnosis confirmed by histological assessment by Memorial Sloan-Kettering Cancer Center (MSKCC) Department of Pathology or by the presence of bone marrow (BM) metastases PLUS elevated urinary catecholamines\r\n* Relapsed or refractory stage 4 disease or relapsed or refractory stage v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN)-amplified 2B or 3 disease
Patients with solid tumors with diagnoses OTHER than neuroblastoma or those listed above will be eligible if they meet both of the following criteria:\r\n* Immunohistochemical demonstration of GD2 expression on cell surface (tumor assessment by immunohistochemistry is required for this group of patients)\r\n* Have refractory or relapsed disease or metastatic disease
Any disease type
Cirrhosis, cardiomyopathy, restrictive heart disease, or bronzing of the skin
Patients who have chronic kidney disease
Patients must have high-risk neuroblastoma with at least ONE of the following:\r\n* Recurrent/progressive disease at any time; biopsy is not required, even if there is a partial response to intervening therapy\r\n* Refractory disease (i.e. less than a partial response to frontline therapy, including a minimum of 4 cycles of chemotherapy); no biopsy is required for eligibility for this study
Patients must have MIBG evaluable disease which is defined as evidence of uptake into tumor at >= one site within 4 weeks prior to entry on study and subsequent to any intervening therapy
Patients with confined liver disease or stable limited extrahepatic disease
Disease is measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (1.1 or original version) or other tumor response criteria from an MSKCC Institutional Review Board (IRB)-approved clinical research protocol\r\n* This criterion does not apply to patients with myeloproliferative neoplasm; the presence of active myeloproliferative neoplasm will be determined by applicable disease-specific diagnostic criteria and patient assessment by the patient’s oncologist and trial investigators (eg, manifestations of active myeloproliferative neoplasm [MPN] such as splenomegaly, abnormal blood counts, etc)
Progressive disease manifest by either;\r\n* Imaging modalities:\r\n** New osseous lesions on bone imaging (bone scintigraphy or sodium fluoride [NaF] PET scan) and/or\r\n** An increase in measurable soft tissue disease, or the appearance of new sites of disease OR\r\n* A minimum of three rising prostate-specific antigen (PSA) values from a baseline that are obtained 1 week or more apart, or 2 or more weeks apart\r\n* PSA changes: \r\n** Androgen-independent, minimum number (No.) of determinations 3, interval >= 1 week, percentage increase over 25%\r\n** Androgen-independent, minimum No. of determinations 2, interval >= 2 week, percentage increase over 25%
Renal (kidney) disease, or solitary kidney
Advanced periodontal disease (gum disease)
At least one site of disease 1.5 cm or greater is needed to meet the spatial resolution limits of PET imaging
Patients with local or regional nodal disease are eligible
Must have surgically curable disease as evaluated by initial imaging by our UNC surgeons
Patients with recurrent disease or a new primary will be allowed
Greater than T3 disease in past and/or treated with prostatectomy
Patients must not have multicentric disease scheduled to undergo multiple lumpectomies; multifocal disease that can be encompassed in a single operative bed are eligible
Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib
Bulky disease (defined as a nodal mass measuring >= 10 cm by CT)
Subjects at increased risk for radiation toxicities, such as known collagen vascular disease (example, scleroderma, Sjogren's disease, etc) or other inherited radiation hypersensitivity syndromes (example, Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.)
Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
Leptomeningeal disease
Dose and Disease Expansion Cohorts
Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment, except concomitant antiviral systemic therapy for chronic hepatitis B or C.
Extramedullary disease only
Failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen
For patients with evidence of minimal residual disease prior to vaccination, assessment of minimal residual disease status by cytogenetics or fluorescence in situ hybridization (FISH) will be followed post vaccination
For cohort 1 only: evidence of disease progression =< 14 months prior to registration according to RECIST 1.1, as confirmed by the site study principal investigator (PI)
Diffuse leptomeningeal disease at recurrence
Primary refractory disease
For patients enrolling once escalation is complete, disease must be measurable per RECIST 1.1 criteria with last imaging performed within 28 days prior to first drug dose In addition to the criterion listed above, Patients in Phase 2a must have a histologically- or cytologically-confirmed, advanced or metastatic solid tumor, in 1 of the following categories: disease history specificied in one of the criteria listed below:
Presence of radiographically suspected leptomeningeal disease (LM) or carcinomatous meningitis (CM) AND/OR presence of at least one CNS lesion for which the following criteria are met:\r\n* For patients without leptomeningeal disease: presence of at least one parenchymal CNS lesion that is at least 5 mm in size; Note: intra-cranial disease assessments can only be performed using contrast-enhanced magnetic resonance imaging (MRI); MRI scan slices of 1 mm are necessary for brain metastases between 5 and 10 mm in size\r\n* The lesion(s) must be newly diagnosed or be present as progression after local therapy, including surgery and/or radiation therapy; for patients who have received local therapy, progression of pre-existing lesions based on RECIST v1.1 (> 20% increase in longest diameter on baseline scan) or new lesions are required\r\n* Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to the first dose of study treatment\r\n* For patients with suspected LM or CM based on imaging, spinal fluid sampling for confirmation is not required; for patients who do undergo spinal fluid sampling, those with negative spinal fluid (CSF) are eligible to enter
Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (e.g. current gallstone disease, alcoholism)
Active inflammatory gastrointestinal disease or previous gastric resection or lap band
Any and all primary disease sites in the abdomen and pelvis will be allowed
No evidence of peritoneal disease on preoperative imaging
Patients with unstable occlusive disease (eg, crescendo angina)
Subjects must be planned for resection (this includes localized resectable disease or patients with metastatic disease with planned palliative resection) and scheduled to begin neoadjuvant chemotherapy
ARM II ONLY: Nonspecific or no evidence for disease on standard imaging modality
- Castration-resistant disease as defined by PCWG2 criteria
Subject has an iron overload disease.
Known to suffer from stable angina pectoris and/or proven coronary disease, or have symptoms suspicious of coronary disease
Progressive disease manifest (within 6 weeks of screening) by either
Blood only collections from patients with partial or stable disease response\r\n* Blood will not be collected from patients whose disease demonstrates ongoing partial response or with ongoing (i.e., prolonged) stable disease given the poor rate of model generation from such samples\r\n* Blood will not be collected from patients between doses within a single treatment cycle
Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation or chemoembolization must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
Known active hyperparathyroid disease or other serious disturbance of calcium metabolism in the past 5 years
Patients must have recurrent disease for which there is a clinical indication for resection
Major or chronic medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator
Current diagnosis of gastroesophageal reflux disease (GERD) with grade >= 3
No active peptic ulcer disease
Leptomeningeal disease
Known hepatobiliary disease or impairment
Major or chronic medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator
If receiving an antiandrogen as part of first-line hormonal therapy, must have shown progression of disease off the antiandrogen prior to enrollment
Have measurable disease that is amenable to a radiographic or ultrasound-guided biopsy or may be biopsied in the office without radiologic guidance.
Carcinomatous meningitis or leptomeningeal disease
Disease duration 10 years or less (RCT)
AND with one or more of the following highly prevalent ambulatory-sensitive chronic conditions (diabetes, hypertension, chronic lung disease, chronic kidney disease, depression, or heart disease).
Any Grady patient who has been consented to receive chemotherapy on trial or as standard of care; there is no restriction by disease site or stage of disease
Has no evidence of disease
Patients who have had a cystectomy or prior diagnosis of muscle invasive disease (T2\n             or greater)
Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria.
AP ? 2.5 x ULN (? 5 x ULN if disease-related).
Target Disease Exceptions
Inability to determine the QT interval on ECG, except for patients with evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.
Inclusion Criteria:\n\n        Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB\n        to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of\n        non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon\n        agreement with the Sponsor, whose disease has progressed despite previous antineoplastic\n        therapy or for whom no further effective standard therapy is available\n\n          -  Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation\n\n          -  Evidence of measurable disease as determined by RECIST v1.1\n\n          -  World Health Organization (WHO) Performance Status ? 2\n\n          -  Negative serum pregnancy test within 72 hours prior to the first study dose in all\n             women of childbearing potential\n\n        Exclusion Criteria:\n\n        Progressive disease following prior treatment with RAF-inhibitors in combination with\n        MEK-inhibitors\n\n          -  Symptomatic or untreated leptomeningeal disease\n\n          -  Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing\n             anti-epileptic drugs\n\n          -  Known acute or chronic pancreatitis\n\n          -  History or current evidence of retinal disease, retinal vein occlusion or\n             ophthalmopathy\n\n          -  Clinically significant cardiac disease\n\n          -  Patients with abnormal laboratory values at Screening/baseline\n\n          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly\n             alter the absorption of oral LGX818/MEK162\n\n          -  Previous or concurrent malignancy\n\n          -  Pregnant or nursing (lactating) women\n\n          -  For addition of LEE011 in the triple combination, congenital long QT syndrome or\n             family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ? 3,\n             brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT\n             >1.5 x ULN.\n\n        Other protocol-defined inclusion/exclusion criteria may apply
In patients with rapidly proliferating disease, hydroxyurea may be administered before study entry, if clinically indicated, to control disease. In such cases, complete hematologic response (CHR) must be sustained for at least 4 weeks for accelerated CML, and at least 8 weeks for chronic phase CML, following the discontinuation of hydroxyurea, to be considered as a CHR.
Only measureable disease (primary or metastatic) is located in or near the thyroid gland, liver, kidney, or urinary bladder.
Time of disease progression.
Current diagnosis of cancer, unstable cardiovascular disease, end-stage liver or kidney disease, or other major medical illness
Stable disease (duration of stable disease must be less than or equal to 6 months) or progressive disease as best response to most recent chemotherapy containing regimen
Relapse/progression based solely on elevation of CA-125, in absence of measurable disease, according to irRECIST criteria.
Leptomeningeal disease
Measureable disease
Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
Patients who have an option for other treatment for B-ALL at the current state of disease.
Auto-immune disease, which:
Current active infectious disease.
Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy