Patients previously treated with CVA21.
Patients treated with prior interleukin-2 (IL-2).
Patients who have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines.
Patients must not have been previously treated with lorlatinib.
Subject who has been previously treated with an anti-CCR4 antibody or an IDO1 inhibitor;
Serum erythropoietin level of > 500 mU/mL in subjects not previously treated with an ESA.
For Group A: Subjects with a history of brain metastases are ineligible. This includes previously treated brain metastases. For Group B (subjects with AML): Active symptomatic CNS involvement of AML. Subjects with previously treated leptomeningeal disease that has been effectively treated are eligible.
Subjects previously treated with any anti-PD-L1 antibody are eligible for study participation).
Patient previously treated with a dose of imatinib > 400mg
The majority of the anticipated target volume (> 50%) must have been previously treated to >= 40 Gy; prior radiation therapy (RT) must have been completed > 6 months prior to initiation of IMRT reirradiation; if previous RT records are unavailable, investigators can estimate the dose to previously treated tissues based on completion notes or other treatment history
Subjects with prior organ transplant or being treated, or anticipated to be treated, with cyclosporine (because long-term administration of the combination of cyclosporine and sirolimus is associated with deterioration of renal function).
Previously treated with an anti-DKK1 therapy
Has been previously treated with an Indoleamine-2,3-dioxygenase-1 (IDO1) inhibitor (e.g., epacadostat, BMS-986205)
AML that transformed from previously treated myelodysplastic syndromes
Patients previously treated with any intra-arterial regional hepatic therapy such as trans-arterial chemoembolization.
Previously treated with pacritinib
Recurrent malignant gliomas previously treated with radiotherapy and/or chemotherapy
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
A washout period of 6-weeks for patients treated last with platinum based chemotherapy. A 2-week washout period for patients treated with all other therapies.
Previously treated with anti-pCAD biologic therapies.
Subjects treated with pemetrexed (pemetrexed disodium) previously will be eligible only if 8 weeks have elapsed between the last dose of pemetrexed and the date of surgery
Patients previously treated on clinical trial with reolysin
Patients must not have been previously treated with chemotherapy or radiation for diagnosis of lymphoma; brief (< 15 days) treatment with glucocorticoids is acceptable
Patients treated with prior Interleukin-2 will be allowed to be in this study
Previously treated in situ carcinoma (i.e., noninvasive)
MCL has been previously treated and has relapsed after or progressed during prior therapy.
Patients who have previously been treated with any of the agents or same class of agents they are scheduled to receive will be excluded. For example, a patient previously treated with a PD1 or PDL1-based therapy will not be eligible for avelumab+4-1BB or avelumab+OX40 arms. A patient previously treated with an OX40 based therapy will not be eligible for any of the OX40 single-agent or combination arms.
Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial.
Pathologically confirmed NSCLC, not previously treated, with a plan to undergo surgery
Pathologically confirmed SCCHN, not previously treated, with a plan to undergo surgery
Patients must be immunotherapy-naive. Those who have previously been treated with conventional chemotherapy for a prior history of sarcoma in the adjuvant setting may be included.
Patients who have previously been treated with talimogene laherparepvec, any other oncolytic virus or pelvic radiation are ineligible
Patients that have previously been treated with daratumumab or ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Phase II Exclusion Criterion Only: Patients previously treated with whole brain radiation therapy (WBRT)
Acute myeloblastic leukemia (AML) that was previously treated with HMA and is unfit for intensive chemotherapy\r\n* Patient must be within 6 months of prior treatment with HMA and must be willing to be treated with the same agent on this study
Subject previously treated with blinatumomab.
Patients previously treated with regorafenib, lonsurf or capecitabine as the last prior regimen can start on this study as long as there is at least 1 week of period between the last dose of previous treatment and day 1 in this study provided the patients are eligible; patients who were on FOLFOX or FOLFIRI regimens must have at least 2 weeks period between the last dose and the first dose in this clinical study; patients previously treated with Avastin, Zaltrap, cetuximab, pembrolizumab, panitumumab, nivolumab Erbitux, and Vectibix must have at least 4 weeks period between the last dose of previous chemotherapy and the first dose in this clinical study
Previously treated with a maximum of 4 cancer-directed treatment regimens.
All patients must have no more than 3 contiguous vertebral body levels treated at a single site, and no more than 3 discontiguous vertebral body levels treated
Previously untreated or treated subjects with no limit on prior lines of systemic therapies are allowed
Has previously been treated with axitinib, AGS-16C3F, or AGS-16M8F
Patients who have previously been treated with avelumab (or another PD1/PDL1 inhibitor) in combination with 5-azacytidine will be excluded
Patients cannot have previously been treated with interferons (e.g., for chronic active hepatitis)
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients who have been previously treated for metastatic melanoma may be included (e.g. prior treatment with v-raf murine sarcoma viral oncogene homolog B [BRAF] inhibitors and/or ipilimumab will be allowed), provided that they have had a three week ‘washout’ prior to signing consent and have not been treated with a PD-1 blocking antibody
Subjects previously treated with CVA21.
Patients with disease only in the bone previously treated with radium-223 will not be eligible
Patients with MDS (up to 20% blasts) of any risk as defined as:\r\n* Previously untreated\r\n* Previously treated with hypomethylating agent (HMA) agent; patients need to have relapsed or progressed after any number of cycles of HMA therapy; patients that do not respond to HMA therapy will also be allowed in the study; relapse or progression will be measured by International Working Group (IWG) 2006 criteria; no response will be lack of clinical benefit after at least 6 cycles of HMA therapy
Patients previously treated with alectinib (Note: this only applies to the phase II portion of the study; participants entering the phase I portion of the study will still be eligible if previously treated with alectinib)
Patients with histologically or cytologically documented, unresectable, Stage IV transitional cell carcinoma of the urothelium who have not been previously treated with first-line chemotherapy.
Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible
NOTE: There is no exclusion for prior immune-based therapy; this includes patients previously treated on Arms 1 or 2 who are otherwise eligible for treatment on Arm 3 or 4
Patients who have previously been treated with nivolumab and/or ipilimumab in combination with 5-azacytidine will be excluded
Patients who have previously been treated with systemic sonidegib or with other Hedgehog (Hh) pathway inhibitors
Patients who have previously been treated with systemic LDE225 or with other hedgehog pathway inhibitors
In the phase II portion of the study, patients that have been previously treated with any systemic therapy for GIST are not permitted to enroll, with the exception of adjuvant imatinib systemic therapy or exposure to imatinib within 4 weeks of signing consent
Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible (Turnstile I)
Patients being treated with certain drugs not acceptable while receiving CFI-400945 fumarate.
Patients who have been treated with vemurafenib will be allowed in this study
Actively being treated on any other therapeutic research study
The subject has previously been treated for the primary diagnosis of OP-SCCA or SG-SCCA
Patients treated with biologics within a specific timeframe
Patients previously treated with RUX or AZA (only applicable for the MF and MDS/MPN arms)
Previously treated participants
Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee
Patients may not have previously been treated with > 1 course of radiotherapy to the brain
Patients may not have previously been treated with radiosurgery to the brain
Actively being treated on any other therapeutic research study
Patients that have previously been treated with ixazomib, or who participated in a blinded study with ixazomib (whether treated with ixazomib or not)
Previously treated in-situ carcinoma (ie, noninvasive)
Patients may have had any number of prior treatment regimens (including biologic) before or after radiotherapy; patients may not have previously been treated with bevacizumab or lapatinib. Gliadel wafers must be approved by CERN Principal Investigator (PI) (Project Leader, Co-Leader and Protocol PI)
Actively being treated on any other therapeutic research study
Actively being treated on any other therapeutic research study
Actively being treated on any other research study
Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible; patients receiving cytotoxic agents will be evaluated by the PI or his designee as to suitable eligibility (Turnstile I)
Patients with stored stem cells will be treated at the escalating dose while patients with no stem cells will be treated at the 50 mCi dose; neuroblastoma patients can be treated at the 50 mCi dose with or without stored stem cells
Previously untreated and treated patients are eligible
Patients previously treated with TLR-7/8 agonist treatment.
Treated with hydroxyurea within 30 days;
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
Women treated previously with 5-fluorouracil or imiquimod or other medications for high-grade squamous intraepithelial lesions will be excluded from the study
Group 2 - patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET rearrangement that was not previously treated with a TKI that inhibits RET.
Patients who have been previously treated with inotuzumab ozogamicin
Patients who have previously been treated with eribulin are allowed to participate in the microdialysis portion of the study only
Patients who have previously been treated with whole brain radiation
Patients may be treatment-naive or may have been previously treated for metastatic disease
Treatment-naïve and previously treated patients will be included; however, patients may not have received a BRAF or HSP90 inhibitor in the past
Subjects previously treated with BRAF or HSP90 inhibitor therapy
Subject has been previously treated with LifeSeal™ Surgical Sealant.
Without confirmed stability over 60 days in patients previously treated with prior surgery or radiation; OR
Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months after treatment;\r\n* NOTE: patient with < 6 moths of life expectancy will be treated with palliative QUAD shot radiotherapy and those with > 6 moths of life expectancy will be treated with conventionally fractionated full dose re-irradiation approach; additional other factors determining which patients will be treated with Quad shot therapy rather than full dose are if the patients have poor performance status, bulky or diffuse disease, significant medical co-morbidities, and significant metastatic disease burden
Subject has been previously treated with mogamulizumab;
Subject must not have been treated previously with talimogene laherparepvec or tumor vaccine.
Without confirmed stability over 60 days in patients previously treated with prior surgery or radiation; OR
Participants previously treated in the recurrent/metastatic setting with any 1 of the 3 SOC therapies in this study (i.e., docetaxel, capecitabine, or gemcitabine) may not receive the same therapy if randomized to the SOC arm. Additionally, participants previously treated in the recurrent/metastatic setting with all 3 SOC therapies are excluded from this study.
were previously treated with CD19-targeted therapy or IMiDs® (e.g. thalidomide, LEN)
Patients must have been previously treated with a taxane except in cases of contraindication (e.g. poor performance status, age or patient choice)
Patients who have previously been treated with cytotoxic chemotherapy; however, patients who received prior low-dose methotrexate for treatment of an ectopic pregnancy will be eligible for this study
Subject who was previously treated with at least one prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.
Patients must have been previously treated, as defined by treatment with at least one prior cytotoxic regimen or agent
Patients treated with TNF antagonists.
Has been previously treated with a Bromodomain and Extra-Terminal (BET) inhibitor
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Patients who have been previously treated in the adjuvant setting for melanoma will be eligible for treatment after a 28 day wash-out period
Previously treated with an anti-Dkk-1 therapy.
Patients are to be treated with hypofractionated RT
Patients must be ipilimumab-eligible. (This includes: 1) patients previously untreated with ipilimumab; 2) patients previously treated (more than 1 year previously) with ipilimumab using a route of administration other than intravenous infusion; and 3) patients previously treated with antitumor agents other than intravenous ipilimumab).
Patients who were previously treated with ipilimumab administered by intravenous infusion.
History of previously treated smoldering myeloma
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.
Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by
Cholangiocarcinoma subjects must have radiographically measurable disease in at least one site not previously treated with radiation, chemoembolization, radioembolization, or other local ablative procedures; a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a radiologist, is acceptable.
Subjects must have radiographically measurable disease in at least one site not previously treated with radiation, chemoembolization, radioembolization, or other local ablative procedures; a new area of tumor progression within or adjacent to a previously-treated lesion, if clearly measurable by a radiologist, is acceptable.
Patients who have not previously been treated with HMA therapy will be excluded
Participants previously treated with bendamustine only if their duration of response was >/= 24 months
Prior malignancy except previously diagnosed and definitively treated more than 3 years prior to trial or whose prognosis is deemed good enough to not warrant surveillance
BCC/SCC that was previously treated (i.e., recurrent BCC/SCC)
Patients who have been previously treated with bendamustine plus rituximab (BR) are eligible, provided they did not progress during or within 6 months of completing BR treatment
Previously treated SCLC with only one prior treatment regimen (cyclophosphamide/doxorubicin/vincristine [CAV] alternating with etoposide/cisplatin [EP] is acceptable)
Treated with at least 1 year of imatinib
Prior therapy allowed: \r\n* Patients may have been previously treated with up to three regimens of oral multikinase inhibitors, including sorafenib, sunitinib and pazopanib\r\n* Patients may have been previously treated with external beam radiation or cytotoxic chemotherapy therapy
Patients may not have been treated with prior sipuleucel-T
Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
Patients previously treated with radiation therapy to the thoracic or lumbar spinal levels of involved disease will not be included
Previously treated with ponatinib
Indications B - LMS: Subjects previously treated with at least one prior line of approved therapy.
Previously treated with a maximum of four unique chemotherapy containing treatment regimens
RAS (KRAS/NRAS) wild type mCRC not previously treated with an anti-EGFR containing regimen (unless contraindicated or not considered standard practice per clinical site or country guidelines).
Patients previously treated with eculizumab for TAM.
Previously enrolled and treated for at least 9 months in Study NEOD001-001
Herceptin: women who have been previously treated with Herceptin or other monoclonal antibody therapies are eligible for the trial
Currently or previously treated with biologic, or immunotherapy
Previously-treated with any conditioning regimen and any GVHD immune suppression prophylaxis and formulation of steroids, except as noted in Exclusion Criteria #2.
Planned to be treated by active surveillance
Patients who have previously been treated with IMGN901
Patients must be untreated or have had only one prior chemotherapy regimen for ALL or LL; previously treated patients will be analyzed separately
Being treated with anti-TNF therapies or has been treated with an anti-TNF therapy within 5 half-lives of randomization.
Currently or previously treated with biologic, small molecule, immunotherapy, chemotherapy, or other agents for metastatic pancreatic carcinoma
Patients previously treated with sunitinib or crizotinib
Tumor must not have been treated previously with radiation
Subjects previously treated on another investigational agent must have a 2-week or more washout before starting cabozantinib, depending on the agent, toxicity profile, and half-life; however, such patients may begin tetracycline dosing after consent is signed
Subjects previously treated with a systemic photosensitizer within 4 months of screening date
Not previously treated with prior anti-cancer therapy for FL
Prior treatment with sirolimus, cyclophosphamide or topotecan: patients previously treated with any of these drugs as single agents will be eligible for this study; patients previously treated with two of the three drugs will also be eligible, however patients previously treated with all three agents in combination will not be eligible; patients previously treated with sirolimus analogues (e.g. temsirolimus, everolimus, or ridaforolimus) are also eligible
The patients may start any Food and Drug Administration (FDA) approved endocrine therapy (with which they have not been previously treated) at week 4 of the trial except for tamoxifen
Patients who have previously been treated with LDE225 or other hedgehog (Hh) pathway inhibitors
Subjects who had been treated with ADI-PEG 20 previously.
Subjects that have previously been treated with a veliparib.
Previously treated; NOTE: no limit to prior therapy provided there is adequate residual organ function
Progressive disease if treated with chemotherapy, radiotherapy, surgery or immunotherapy. If prior radiation was given, the measurable disease should be outside the radiation port. Unequivocal progression of HCC/BTC lesions previously treated with catheter-based therapy including transarterial chemoembolization or radioembolization is allowed.
Subjects who had been treated with ADI-PEG 20 previously.
Patients previously treated with systemic chemotherapy will be eligible
Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors
Maintenance of Lupron or antagonist unless previously treated with orchiectomy
Subjects that have previously been treated with dacarbazine or its analogue temozolomide or eribulin.
If previously treated with bortezomib (alone or in combination), progression during treatment
If previously treated with a lenalidomide and dexamethasone (len/dex) combination:
Patients diagnosed with alcoholism may not be treated with disulfiram
Has been treated with mastectomy
Patients previously treated with radioactive isotope (e.g. strontium [Sr]89) within 30 days of randomization
Patients previously treated with anti-GITR therapy.
Women who will be treated at the Johns Hopkins Hospital, Sibley Memorial Hospital or who will be treated by oncologists in the community as long as we will have access to treatment records
All patients must have no more than 3 contiguous vertebral body levels treated at a single site, and no more than 3 discontiguous vertebral body levels treated
Parents of childhood cancer survivors who are now 18 years or older and who were previously treated for ALL or AML (do not need to live with the child)
Patients may have been previously treated or previously untreated
Patients will receive repeated cycles of identical chemotherapy that will likely result in grades III-IV hematological toxicity; patients will be treated outside of Children’s Oncology Group (COG) protocols with specific requirements for schedule of G-CSF administration; the following categories of patients treated at Children’s Hospital of Michigan are eligible for this study:\r\n* Patients with brain tumors treated according to modified Head Start II protocol with vincristine, etoposide, cyclophosphamide, and cisplatin (OPEC) chemotherapy;\r\n* Patients with recurrent Hodgkin lymphoma treated with ICE (ifosfamide, carboplatin, etoposide) chemotherapy;\r\n* Patients with recurrent solid tumors including sarcomas, Wilms’ tumor, neuroblastomas, or brain tumors treated with high dose ICE or ICT (ifosfamide, carboplatin, topotecan) chemotherapy
Patients who have previously been treated with systemic LDE225 or with other Hedgehog (Hh) pathway inhibitors
Will be treated according to the Armstrong method
Cancer patients without BRONJ who have been treated with intravenous zoledronate for >= 1 year duration
Subject is diagnosed with neuroblastoma, hepatoblastoma, osteosarcoma or extracranial germ cell tumors and has not been previously treated with cisplatin or carboplatin.
Liver nodule previously treated with trans-arterial or thermal ablation
Patients who have been or are anticipated to be treated with radiosurgery
Previously treated with any prior mIDH1 targeted therapy
Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
Tumor previously treated with radiation therapy
Has locally recurrent inoperable breast cancer not previously treated with chemotherapy and which cannot be treated with curative intent OR has metastatic breast cancer not previously treated with chemotherapy.
For patients to be treated with a regimen containing bevacizumab:
Patients with prior treatment with bevacizumab (or any other anti vascular therapy, e.g., cediranib) for platinum resistant recurrence; (Note: prior bevacizumab in initial therapy and/or platinum sensitive recurrent setting is allowed)
Prior bevacizumab therapy is excluded.
Patients who have received prior therapy with bevacizumab, or related drugs (previous therapy with carboplatin is allowed)
Has received trebananib or another angiopoietin-2 directed therapy (prior treatment with bevacizumab is not an exclusion criteria)
Patients must not have received prior anti-VEGF therapy including bevacizumab (i.e. patients must be bevacizumab naive)
Prior bevacizumab
Patients who have had previous treatment with bevacizumab
There is no limit on the number of prior relapses but the most recent relapse must be the first relapse on a bevacizumab-containing regimen
Patients who have received investigational or licensed drugs that target vascular endothelial growth factor [VEGF] or VEGF receptors/pathways (such as bevacizumab, sorafenib, pazopanib, sunitinib, axitinib, cabozantinib, etc.) for the treatment of recurrent cancer are not eligible; exceptions: prior treatment with bevacizumab in the up-front or maintenance setting is allowed, provided the patient had a favorable response to bevacizumab; favorable response is defined as having had a disease free interval of > 6 months following completion of a bevacizumab-containing regimen; if questions, contact the principal investigator (PI)
Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naive – groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed – groups 2 and 4); therapy with these agents may be given together or sequentially in the past
Patients must be considered bevacizumab-resistant, i.e.; have a treatment-free interval following a response to bevacizumab (complete response [CR], partial response [PR], or stable disease [SD]) of less than 6 months, or have progressed during treatment with a bevacizumab-containing therapy
If participant was treated with bevacizumab, at least 4 weeks must elapse before treatment with either agent (cyclophosphamide or rQNestin34.5v.2)
For biopsy cohort, participants must be bevacizumab naive or received the last bevacizumab treatment at least 12 months prior to Cycle 1 Day 1 and according to the investigator's judgment the planned biopsies would not expose participants to substantially increased risk of complications
Patients may have had previous systemic treatment regimens (no limit to number of prior therapies); patients with prior treatment with bevacizumab are eligible for enrollment into the study; NOTE: except for bevacizumab, a 28 day wash-out period prior to registration is mandatory for all systemic treatments
Prior use of bevacizumab
Patients may not have had prior bevacizumab, based on case reports of tracheoesophageal fistula in patients treated with bevacizumab and radiotherapy
Patients who have had any prior bevacizumab, due to case reports suggesting a possible risk of severe toxicity in combination with radiotherapy
Prior treatment with any anti-angiogenic agent (including bevacizumab)
Patients may have received previous NY-ESO-1 vaccine therapy; patients who received maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have discontinued therapy (at least 4 weeks for prior taxane or prior bevacizumab) prior to randomization and recovered from toxicities to less than grade 2
Only patients for whom their neuro-oncologist has planned to give bevacizumab and temozolomide 50mg/m^2/day as part of their treatment are eligible for this study
Patients who have had previous treatment with bevacizumab and/ or NovoTTF 100A system
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
Bevacizumab within the last 3 weeks before enrollment on trial
Bevacizumab naive
(Bevacizumab-related exclusion) Known hypersensitivity to any component of bevacizumab
Patients must not have received prior treatment with bevacizumab.
Be at least 14 days from the last administration of bevacizumab
Has previously received treatment with bevacizumab
Patients with prior bevacizumab use for tumor treatment; patients who received bevacizumab for symptom management, including but not limited to cerebral edema, pseudoprogression can be included in the study
Have adequately recovered from second look surgery to be able to start bevacizumab within 7 weeks of this procedure
Participant may have received bevacizumab (or other antiangiogenic agent) and/or cyclophosphamide in the past
Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab
Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 4 weeks
Patients may have received prior targeted therapy such as bevacizumab
Bevacizumab® or other anti-angiogenic therapy.
Prior therapy with bevacizumab
Subjects must not have received capecitabine or bevacizumab for this disease
Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO criteria.
Has been treated previously with bevacizumab
Patients previously treated with bevacizumab.
COHORT II: Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment)
Bevacizumab-naive – no prior exposure to bevacizumab
Patients who have received previous anti-angiogenic treatment (experimental or marketed: bevacizumab, thalidomide, CP-547632, sunitinib, sorafenib or others)
Patients with an impending fracture who have had bevacizumab are eligible provided there will be a 3-week window between their last infusion and surgery
Prior therapy with bevacizumab, liposomal doxorubicin, or everolimus
Prior treatment with bevacizumab within 12 weeks of study entry
Treated with antiangiogenic agents (like bevacizumab) within 4 weeks before biopsy
Patients receiving bevacizumab within 12 weeks prior to protocol treatment
Prior treatment with bevacizumab
Current or recent (within 10 days prior to first dose of bevacizumab) use of aspirin (> 325 mg/day)
No more than 2 prior chemotherapies and 1 relapse; prior bevacizumab therapy is allowed
Patients may not have previously been treated with bevacizumab or lapatinib
Patients treated with any systemic anti-cancer therapy for NSCLC within 21 days prior to randomization (6 weeks for Bevacizumab).
Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids.
Patients who have undergone prior resection, radiation therapy, and/or chemotherapy (except bevacizumab)
Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
Patients who have received bevacizumab, Gliadel, or are on active therapy with Optune are not eligible
Known hypersensitivity to inactive ingredient of bevacizumab
Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)
Arm 1 patients must have not received bevacizumab previously
Arm 2 patients must have progressed/recurred on bevacizumab as the most recent regimen; patients on arm 2 should continue on bevacizumab as clinically necessary to control brain edema
Patients who have been off bevacizumab for < 30 days prior to baseline MRI
Patient is to receive bevacizumab as maintenance treatment
No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for this disease; chemotherapy drugs and bevacizumab may be stopped and started as long as no prior disease progression requiring change in chemotherapy agents occurred
Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting.
Have received more than one prior antiangiogenic agent (that is, bevacizumab, sorafenib, sunitinib) for TCC of the urothelium.
Patients who will be enrolled under protocol amendment # 2 must have previously received bevacizumab, either discontinued due to intolerability, or progressed after at least 2 cycles of bevacizumab
Continued treatment with bevacizumab with documented evidence of disease progression on a bevacizumab-containing regimen
At least 21 days since the last dose of bevacizumab, other antibody, or interferon.
Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids
An interval of >= 4 weeks after the last administration of any investigational agent or prior cytotoxic therapy (except bevacizumab); there should be 14 days interval between the last dose of bevacizumab and first day of treatment on study
Prior treatment with bevacizumab within twelve weeks before the first infusion.
Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting.
Patient has previously received standard of care chemo-radiation with temozolomide, ± adjuvant temozolomide and bevacizumab and now has radiographic evidence of recurrent/progressive GBM or GS during or after bevacizumab.
Participants who have received prior bevacizumab are eligible unless there is evidence of unacceptable toxicity due to prior bevacizumab exposure
Capecitabine and bevacizumab considered appropriate treatment for the patient
Intolerance to bevacizumab defined as any NCI CTCAE grade 3 or grade 4 toxicity attributed to this agent that required discontinuation of bevacizumab (e.g., arterial thromboembolism [ATE], perforation, wound healing difficulty, proteinuria, reversible posterior leukoencephalopathy syndrome [RPLS]); Note: patients with prior grade 3 bevacizumab-related hypertension may be permitted if hypertension was manageable with standard oral antihypertensives as so judged by the treating physician
Previous therapy with bevacizumab is allowed, but patient who experienced serious dose-limiting toxicities while on prior bevacizumab therapy are excluded
Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as bevacizumab
Has been treated previously with bevacizumab
Treatment with bevacizumab in at least one prior line of therapy for metastatic disease
Advanced unresectable, metastatic or recurrent colorectal carcinoma (CRC) for which treatment with FOLFOX6 with or without bevacizumab, FOLFIRI with or without bevacizumab, CAPOX, or regorafenib would be acceptable as determined by the Investigator. FOLFIRI-refractory patients with CRC enrolling on the FOLFIRI study arm must have failed treatment with one FOLFIRI with or without bevacizumab regimen for unresectable or metastatic disease. Treatment failure is defined as progression of disease (clinical or radiologic) during treatment with FOLFIRI with or without bevacizumab or < 3 months after the last dose of treatment with FOLFIRI with or without bevacizumab. Patients with CRC enrolling on the regorafenib arm of this study will have previously received at least two previous lines of therapy for advanced colorectal cancer, and will have previously received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Patients with K-ras wild type tumors enrolling on the regorafenib arm will also have previously received either cetuximab or panitumumab.
For patients to be treated with a regimen containing bevacizumab:
Patients who have received previous treatment with bevacizumab for CNS disease are not eligible for participation
Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab
Prior treatment with doxorubicin and/or bevacizumab
Patients who have had prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib
Prior treatment with bevacizumab
FOR COHORT 1: (BEVACIZUMAB ELIGIBLE)
FOR COHORT 2 (BEVACIZUMAB INELIGIBLE):
Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 2 weeks
BEVACIZUMAB-SPECIFIC EXCLUSIONS:
BEVACIZUMAB-SPECIFIC EXCLUSIONS
Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naive - groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed -groups 2 and 4); therapy with these agents may be given together or sequentially in the past
For bevacizumab-naive patients (groups 1 and 3) a minimum of 6 months must have elapsed since completion of radiation therapy for study entry, and there is no minimum time since completion of last chemotherapy; for bevacizumab-exposed patients (groups 2 and 4) no minimum time since completion of last radiation therapy, biologic agents, or chemotherapy will be required for study entry
Prior use of pazopanib or other agents targeting angiogenesis pathway (such as bevacizumab, sunitinib, or sorafenib) in the metastatic setting
Prior disease progression/recurrence during or immediately following treatment with bevacizumab; any questions should be directed to the PI
Patients who have had prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C); patients must be off treatment with temozolomide for at least 23 days; patients who received non-cytotoxic drug therapy must be off treatment for at least 2 weeks; for patients enrolling in Part 1 or Part 3 AND who have progressed on a prior bevacizumab-containing regimen, patients may continue treatment with bevacizumab 10 mg/kg monotherapy, with last dose of bevacizumab administered no fewer than 14 days from start of plerixafor and bevacizumab; for participants enrolling in Part 1 or Part 3 AND who have progressed on a prior anti-VEGF(R) (other than bevacizumab) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days before receiving plerixafor and bevacizumab; for patients enrolled in Part 2 (surgical substudy) AND who have progressed on a prior bevacizumab or other anti-VEGF(R) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days prior to surgery; NOTE: participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide); for any patient who received prior bevacizumab or an anti-VEGF(R) therapy, patient must NOT have discontinued that treatment regimen due to a treatment-related toxicity
Patients must be at least 48 hours from placement of central catheter before receiving first dose of bevacizumab
Patients must be willing to forego other drug therapy against the tumor while being treated with bevacizumab and temozolomide
Subjects who have progressed on Bevacizumab treatment
(continued from no. 22) Subjects will be apprised of the large potential risk to a developing fetus. It is not known whether bevacizumab is excreted in human milk. Because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women. Patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy.
Previous bevacizumab within 6 weeks prior to enrollment
Prior treatment with bevacizumab is not allowed.
1st progression of GBM on bevacizumab-containing regimen or within 8 weeks of discontinuing bevacizumab. In either case, must have received a minimum of 8 weeks (4 infusions) of bevacizumab.
14 days from last dose of bevacizumab
Known hypersensitivity to any inactive ingredient of bevacizumab
Prior chemotherapy for recurrent glioblastoma with nitrosourea compounds or bevacizumab
Bevacizumab will be allowed for patients with non-squamous carcinoma. Prescribing information must be followed and precautions have to be taken into consideration (e.g., patients having presented a serious hemorrhage or recent hemoptysis should not receive bevacizumab).
Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
Bevacizumab within 4 weeks.
Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
Prior treatment with bevacizumab within twelve weeks before the first infusion.
For those receiving bevacizumab, standard medical exclusionary conditions apply
Participants with newly detected enhancement are eligible, with bevacizumab treatment hoped to prevent symptoms
- bevacizumab or aflibercept
Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
Prior therapy with bevacizumab or other VEGF pathway targeted therapy in the recurrent setting; bevacizumab in the upfront setting is allowed
Bevacizumab-refractory patients: these patients may not have more than 2 prior relapses not counting the current relapse being treated by this protocol and must have received multiple chemotherapy regimens, including a temozolomide regimen and a bevacizumab regimen
Planned to receive bevacizumab
The last dose administered of bevacizumab must be at least 21-days but not more than 56-days from enrollment
Last dose of bevacizumab >= 2 weeks prior to registration (Phase I); note: for the phase II study only, prior exposure to bevacizumab is not allowed
Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)
Patients enrolling onto Cohort 2b who have been taken off bevacizumab must have had at least a 28 day washout from any previous administration of bevacizumab. It is preferred that patients who fail bevacizumab prior to trial entry remain on bevacizumab in the trial.
Received prior bevacizumab therapy or had clinically documented reason why not administered
Medical conditions that would contraindicate bevacizumab therapy in non-squamous NSCLC (Arms C, D, E, and F)
Subjects receiving bevacizumab for maintenance therapy are excluded (subjects who received bevacizumab as part of their adjuvant therapy will be permitted)
Has received bevacizumab within 4 weeks prior to randomization
No bevacizumab =< 3 months of study registration
Failure on bevacizumab (either as a monotherapy or a combination) as most recent regimen confirmed by tumor recurrence on MRI.
The patient must have failed no more than one regimen of bevacizumab.
There must be a minimum of 14 days (i.e., an interval equal to or greater than 14 days) since last treatment with bevacizumab and registration
Prior allergic reaction to bevacizumab or severe adverse event with bevacizumab.
Prior therapy with bevacizumab
BEVACIZUMAB-SPECIFIC EXCLUSIONS
Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-FU, nab-paclitaxel (or other taxanes) or gemcitabine Exclusion Criteria Specific to Bevacizumab-Containign Arms (Arms A, B, and F) (Patients who meet any of the following criteria will be excluded from enrollment into bevacizumab-containing Arms A, B, and F:)
Anti-angiogenic agents including bevacizumab: 4 weeks
Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to administer bevacizumab, either as single therapy or in conjunction with other chemotherapeutic regimens, in order to treat tumor progression/recurrence per the treating physician; patients receiving bevacizumab primarily for reduction of edema (i.e. alleviation of symptoms) rather than for tumor treatment are excluded
Patients who have not previously received a bevacizumab-containing regimen (i.e., this must be the first bevacizumab-containing therapy administered to the patient)
Patient must be scheduled to receive treatment with a bevacizumab containing chemotherapy regimen; patient can be treated with bevacizumab alone or in combination with other chemotherapies; patient may also be receiving treatment with Optune
For cohort A, only patients for whom their neuro-oncologist has planned to give bevacizumab with lomustine are eligible for this study
For cohort B, only patients for whom their neuro-oncologist has planned to give bevacizumab monotherapy are eligible for this study
Platelets >= 75,000/mcL for bevacizumab monotherapy cohort; > 100,000/mcL for bevacizumab + lomustine cohort
Prior use of ibrutinib is allowed unless patient has had disease progression while receiving ibrutinib
Subject must be referred for treatment with ibrutinib.\r\n* Since ibrutinib will not be supplied as part of the study, the subject’s ability to obtain ibrutinib from a commercial supplier must be confirmed prior to enrollment
Concurrent enrollment in another therapeutic investigational study or have previously taken ibrutinib and/or lenalidomide.
Prior exposure to ibrutinib or ulocuplumab
Patients who are receiving any other investigational agents; all investigational agents other than ibrutinib must have been discontinued at least 4 weeks prior to beginning treatment; prior ibrutinib therapy must have been discontinued at least 2 weeks prior to beginning therapy
Completion of any prior treatment with radiation, chemotherapy, biologics, and/or other investigational agents at least 4 weeks prior to the first dose of ibrutinib; patients must have completed any prior immunotherapy (e.g., rituximab or PD-1 inhibition) or antibody drug conjugate therapy (e.g. brentuximab vedotin) at least 4 weeks prior to the first dose of ibrutinib in the absence of clear disease progression
Participants who have had prior exposure to ibrutinib
Prior use of ibrutinib
Cohort #2: prior treatment with ibrutinib is allowed; patients should not have received any anti-lymphoma therapy within 3 weeks from start of study treatment, with the exception of ibrutinib
Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in the treatment course. Patients may have received other therapies after ibrutinib but stopped based on the defined wash-out periods and still meet iwCLL criteria for treatment
Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy
Lack of a complete response after receiving ibrutinib for > 1 year OR presence of known ibrutinib resistance mutation
Prior therapy with ibrutinib or other BTK inhibitors
Prior therapy for lymphoma including chemotherapy or immunotherapy including ibrutinib/anti-CD20 agents; patient may have received corticosteroids, but should be off them 2 weeks prior to study entry; known prior significant hypersensitivity to obinutuzumab (not including infusion reactions) or ibrutinib
Patients must have a diagnosis of CLL/SLL and EITHER have high-risk cytogenetic features or molecular features, defined as: del(17p), del(11q), mutated TP53, complex metaphase karyotype (defined as >=3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis) OR have developed a BTK or PLCG2 mutation, detected by sequencing and have not developed disease progression during ibrutinib therapy as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria OR B2M has not normalized after at least 1 year (yr) on ibrutinib therapy\r\n* Note: some patients treated with ibrutinib may no longer have detectable fluorescence in situ hybridization (FISH), karyotypic or molecular abnormalities after 12 months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken within the 3 months prior to starting ibrutinib or at some time during their ibrutinib therapy and analyzed at a Clinical Laboratory Improvement Act (CLIA)-accredited laboratory
Patients must have received at least 12 months of ibrutinib therapy and have measurable CLL by at least one of the following: Absolute monoclonal lymphocyte count > 4000/microL; OR measurable lymph nodes with at least one node > 1.5 cm in diameter on computed tomography (CT); OR Bone marrow with >= 30% lymphocytes or peripheral blood specimen taken within the 3 months prior to starting ibrutinib or at some time during their ibrutinib therapy and analyzed at a CLIA-accredited laboratory
Prior treatment with either venetoclax or ibrutinib
Patients should be previously untreated or have only been treated with single agent ibrutinib therapy for a period of < 3 months and were deemed ibrutinib intolerant
Participants who have previously received ibrutinib for another indication
Prior therapeutic intervention with any of the following:\r\n* Therapeutic anticancer antibodies within 4 weeks (rituximab), except within 6 months for obinutuzumab or a similar investigational type II monoclonal antibody;\r\n* Radio- or toxin-immunoconjugates within 10 weeks;\r\n* Inhibitors of BTK (ibrutinib), PI-3K (idelalisib), BH3-mimetic venetoclax, lenalidomide and other “targeted” therapy (including but not limited to investigational BTK and PI-3K inhibitors, etc.) – within 6 half-lives (i.e., 36 hours for ibrutinib)\r\n* All other chemotherapy, radiation therapy within 3 weeks prior to initiation of therapy\r\n* SYK inhibitors at any time
History of treatment with ibrutinib or blinatumomab
Has progressed on prior therapy with ibrutinib or other BTK inhibitors
Known hypersensitivity to either study drug (umbralisib or ibrutinib)
Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 4 weeks prior to the first dose of the study drugs (except ibrutinib for patients in cohort 3); NOTE: for patients on oral targeted therapies (such as ibrutinib, idelalisib, IPI-145, ACP-196), a wash-out of 3 days from cycle 1 day 1 is acceptable
Prior treatment with venetoclax or ibrutinib
Patients previously treated with ibrutinib > 14 days are ineligible; if patient has been treated with ibrutinib for < 14 days, it must be discontinued 1 week (7 days) weeks prior to study initiation
Patients must be currently receiving ibrutinib for at least 6 months prior to enrollment in the study and:\r\n* Not experiencing any >= grade 2 non-hematologic ibrutinib-related toxicity\r\n* The best response to ibrutinib therapy must not have exceeded partial response or stable disease (i.e. no complete response [CR] or complete response with incomplete marrow recovery [CRi])\r\n* Note: patients carrying a deletion at chromosome 17p (i.e. deletion [del][17p]), and/or tumor protein (TP)53, Bruton's tyrosine kinase (BTK), and at the phospholipase C, gamma 2 (PLCgamma 2) loci mutations, will be eligible if they are receiving frontline therapy with ibrutinib
Patients that previously were treated with ibrutinib for > 7 days
Previous chemotherapy, immunotherapy, biologically targeted therapy, other investigational agent, or radiation therapy within 3 weeks of initiation of ibrutinib therapy or radio-immunotherapy within 12 weeks of initiation of ibrutinib therapy
No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
Subjects experiencing toxicity with ibrutinib
Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose
No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
Subjects experiencing toxicity with ibrutinib
Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose
Currently taking ibrutinib and first took ibrutinib > 3 months ago
Inability to continue taking ibrutinib for any reason
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)
Intolerance of ibrutinib
History of allergy to or intolerance of ibrutinib or lenalidomide
Prior exposure to ibrutinib or other ITK inhibitors
A treatment regimen containing ibrutinib unless patient is not a candidate
Patients who have been previously treated with ibrutinib (or any Bruton’s tyrosine kinase inhibitor) are eligible for the ibrutinib pre-treated cohort as long as prior ibrutinib or BTK inhibitor therapy was not discontinued due to toxicity/adverse event; there is no minimum dose of ibrutinib; any prior administration will disqualify patients for the ibrutinib-naïve cohort and will require enrollment on the ibrutinib pre-treated cohort
Eligible and able to secure sourcing for ibrutinib
Previous treatment with ibrutinib
Intolerant of ibrutinib
Ongoing AE attributed to ibrutinib therapy
Treatment with systemic anticancer therapy for CLL is prohibited between discontinuation of ibrutinib and enrollment on this trial.
CLL requiring treatment; patients must be eligible for ibrutinib therapy
Patients who have received any treatment with ibrutinib prior to study entry
Previous treatment with ibrutinib
History of hypersensitivity to ibrutinib
For the ibrutinib arm only: participants must not currently require ongoing anticoagulation for any reason, or have had any major bleeding events within 6 months of enrollment
Known hypersensitivity to ibrutinib or any component of the ibrutinib formulation
Prior use of ibrutinib or other BTK inhibitors, rituximab or lenalidomide
Prior treatment with ibrutinib
Known hypersensitivity to ibrutinib
Participants who are receiving any other investigational agents\r\n* Patients who have previously received ibrutinib will be ineligible in the Phase Ib portion of the study of the CLL arm\r\n* MCL patients who have been on ibrutinib for less than 6 months (180 days) from the time of registration are eligible in the Ib portion of the trial; no washout will be required
Treatment with chemotherapy, monoclonal antibodies or biological agents (e.g. ibrutinib, lenalidomide) within 28 days prior to entering the study
Prior exposure to ibrutinib or other BTK inhibitors.
Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must have received previous treatment as follows:
Subjects in the ibrutinib + JCAR017 combination therapy cohort must be either:
receiving ibrutinib and progressing at the time of study enrollment
have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib
Prior therapy with ibrutinib or venetoclax
Patients may have received prior ibrutinib, lenalidomide, rituximab, and/or bortezomib either alone or in combination
Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib
Concurrent enrollment in another therapeutic investigational study or have previously taken ibrutinib
Prior treatment with ibrutinib
Patients who have previously received treatment with ibrutinib (modified by amendment 1), including:
Discontinuation of ibrutinib treatment at an earlier time due to toxicity
Prior exposure to ibrutinib
Prior exposure to ibrutinib
Receipt of any investigational agents within 14 days before the first dose of ibrutinib
Known hypersensitivity to ibrutinib or nivolumab
Subject must currently be participating in an ibrutinib clinical trial, deriving clinical benefit from treatment with ibrutinib in the opinion of the treating physician and do not have access to commercial ibrutinib within their region.
Ongoing continuous treatment with ibrutinib.
Subject must have completed all assessments in their parent protocol and want to continue treatment with ibrutinib.
Meeting any requirement in the parent protocol to permanently discontinue ibrutinib treatment.
PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT)
Prednisone equivalent of > 2m/kg for treatment of GVHD prior to administration of ibrutinib
Prior treatment with either obinutuzumab or ibrutinib
INCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION)
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Karnofsky performance status < 60%
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Any uncontrolled active systemic infection
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Lactating or pregnant
Concurrent enrollment in another therapeutic investigational study or prior therapy with ibrutinib or other BTK inhibitors
Patients must have been receiving single agent ibrutinib therapy at the time of disease progression; patient may have received other therapy in combination with ibrutinib earlier in their treatment course; prior obinutuzumab therapy is also permitted
Patients must have progressive disease on single agent ibrutinib therapy (but not within the first 2 months of initiating ibrutinib therapy); progression is based on 2008 iwCLL definition, but excluding patients who have treatment-related lymphocytosis as the sole progressive factor; therefore, patients must have at least one of the following:\r\n* >= 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be >= 2 cm); appearance of new palpable lymph nodes\r\n* >= 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly, which was not previously present\r\n* Decrease in hemoglobin >= 2 gm/dL, or decrease >= 50% in platelet or granulocyte count with a bone marrow biopsy showing CLL cell infiltrate\r\n* Progressive lymphocytosis, >= 50% higher than lowest absolute lymphocyte count (ALC) on single agent ibrutinib therapy, excluding ibrutinib treatment-related lymphocytosis\r\n* If receiving ibrutinib as part of a clinical trial: meets criteria for disease progression based on trial defined criteria
Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy
Subject has received bevacizumab (Avastin).
Receipt of bevacizumab (Avastin) therapy within 4 weeks of scheduled M032 administration; (receipt of bevacizumab [Avastin] greater than 4 weeks of scheduled M032 administration does not exclude patient)
Use of Avastin in the preceding two weeks or planned use in the forthcoming two weeks and VEGF inhibitors within + 30 days of treatment
May have received 1 prior biologic regimen (i.e. avastin) but not within 4 weeks of enrollment
Patients with gliomas who have had prior treatment with bevacizumab (Avastin) are excluded
Avastin use within 30 days prior to surgery.
No prior therapy with Avastin
Prior or concurrent treatment with Avastin (bevacizumab)
Any patients planning to receive Avastin or any other anti-angiogenic drugs
Prior antiangiogenic therapy (e.g., Bevacizumab/Avastin)
Has the subject received Avastin® (bevacizumab) for this recurrence/progression, or within the 4 weeks prior to planned Visit 1?
Have received any prior treatment with bevacizumab (Avastin).
received Avastin
Patients must be scheduled to receive: 1) standard chemotherapy with/without radiation therapy; OR 2) single-agent bevacizumab (Avastin)