Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
Patient must have developed disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], methotrexate-vinblastine-doxorubicin-cisplatin [MVAC], carboplatin, gemcitabine [CarboGem]) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or must be unfit or ineligible for cisplatin-based chemotherapy; there is no restriction on the number of prior lines of chemotherapeutics agents received\r\n* Patients who progressed within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant regimen are considered second-line patients; therefore, these patients may be also eligible\r\n* Patients who are unfit or ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria are eligible for this trial: \r\n** Eastern Cooperative Oncology Group (ECOG) performance score of 2\r\n** Creatinine clearance < 60 mL/min \r\n** A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies \r\n** Grade >= 2 peripheral neuropathy
More than one prior chemotherapy-containing line(re-challenge with the same initial regimen is not allowed)
Patients who never received platinum-containing regimen for Small-cell Lung Cancer (SCLC)
Maintenance or switch maintenance therapy after first-line chemotherapy will be considered part of the first-line regimen and is acceptable. Participants who completed and progressed on a platinum-containing regimen as adjuvant, neoadjuvant, or part of a course of chemoradiation therapy given from locally advanced disease and developed recurrent (local or metastatic) disease within the 6 months before screening would be counted as having received 1 prior platinum-containing regimen and therefore would not require re-treatment with a platinum-containing regimen for Stage IIIB, IV, or recurrent disease and are eligible. However, participants must have received at least 2 cycles of a platinum doublet based chemotherapy before discontinuation for toxicity. If participants received only one cycle of a platinum doublet and discontinue due to clear progression, that regimen should be counted as a prior line of therapy.
Second-line patients who have disease progression during or following platinum-containing chemotherapy.
Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Known allergy to eggs, gentamicin, or platinum containing compounds
Prior treatment with any methotrexate containing systemic regimen within 1 year (excluding intrathecal methotrexate)
Prior treatment with 89-Strontium or 153-Samarium containing compounds (e.g. Metastron®, Quadramet®)
History of, or known, hypersensitivity to gemcitabine or platinum-containing compounds.
Prior treatment with gemcitabine or platinum-containing compounds, including in the adjuvant setting.
Radiologic evidence for progressive disease after >= 1 prior platinum containing chemotherapy regimen in the perioperative or metastatic setting
Platinum-resistant or platinum-refractory disease, defined as either 1) less than a complete response to the most recent carboplatin- or cisplatin-containing chemotherapy regimen, 2) serum cancer antigen (CA)-125 >= 2 x upper limit of normal (ULN) within 180 days of last dose of carboplatin- or cisplatin-containing chemotherapy, confirmed by a second CA-125 (the second CA-125 does not have to be within 180 days of chemotherapy), or 3) CT or positron emission tomography (PET)/CT evidence of cancer recurrence within 180 days of last dose of carboplatin- or cisplatin-containing chemotherapy
Subjects must have relapsed after at least one prior purine analogue-containing regimen (fludarabine, cladribine or pentostatin), OR at least two non-purine analogue containing regimens
Patients must have received at least one prior therapy for CLL comprised of the following:\r\n* ? 1 regimen containing an anti-CD20 antibody (e.g., rituximab, obinutuzumab) administered for ? 2 doses\r\n* ? 1 regimen containing ? 1 cytotoxic agent (eg, bendamustine, fludarabine, chlorambucil, cyclophosphamide) administered for ? 2 cycles
Presence of measurable AML that has progressed during or relapsed after prior therapy, including ?1 regimen containing a FLT3 kinase inhibitor.
Have stable disease or progression on a prior regimen containing infusional 5-FU or capecitabine according to the interpretation of the treating provider
Letrozole combination cohort (L): metastatic breast cancer (MBC) with progression who are candidates for a letrozole-containing regimen, with palbociclib.
Evidence of progressive disease (PD) on or within 6 months of a platinum (cisplatin or carboplatin) regimen: at least 1 prior regimen must have contained a platinum-taxane combination
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, noncytotoxic agents or extended therapy administered after surgical or non-surgical assessment
Prior progression on only 1 line of chemotherapy in the advanced/metastatic setting containing a fluoropyrimidine and/or platinum compound
Progression after treatment with least one platinum containing chemotherapy regimen
Histologically confirmed metastatic non-small cell lung cancer (NSCLC) with disease recurrence or progression during or after prior platinum-containing doublet chemotherapy regimen
Experienced progression following a regimen containing an alkylating agent.
Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen.
Either ineligible for first-line cisplatin-based chemotherapy or have disease progression during or following treatment with at least one platinum-containing regimen.
Patient has received prior treatment with AM0010 or fluoropyrimidine/platinum containing regimen
Patients who were intolerant of a gemcitabine containing regimen.
Must have received at least one line of standard systemic treatment for locally advanced or metastatic disease setting of the respective tumor type; for NSCLC, it is either PD-1/PD-L1 inhibitor, or platinum-containing chemotherapy, or an EGFR tyrosine kinase inhibitor or an ALK inhibitor if sensitizing mutation present; TNBC: platinum-containing chemotherapy; PDAC: fluorouracil (5-FU-), gemcitabine-, or taxane-containing chemotherapy either with or without radiation therapy; SCLC: platinum-containing chemotherapy for limited or extensive stage disease
Estrogen containing compounds for > 2 months prior to enrollment
For subjects in Group A with neuroendocrine prostate cancer (NEPC), previous use of at least one platinum-containing chemotherapy regimen
Patients must have received prior treatment with a platinum containing regimen and may have received an unlimited number of prior regimens (including prior taxanes)
Prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine, or study drugs involved in this protocol, or to a monoclonal antibody or prior hypersensitivity to platinum-containing agents
Meets one of the following criteria: Is currently on a stable regimen of an oral contraceptive containing 1mg NE and 0.035mg EE, or Is willing to switch to a regimen of an oral contraceptive containing 1mg NE and 0.035mg EE from a stable regimen of an alternate OC, or Is willing to start a regimen of an oral contraceptive containing 1mg NE and 0.035mg EE.
Phase I/IB (pre-treated): have progression from at least one prior line of therapy; maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy; subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible for these arms; subjects with recurrent disease >= 6 months after completing a platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a systemic regimen given to treat the recurrence, must have received another treatment in the first-line metastatic setting
At least 1 prior chemotherapy regimen containing cisplatin or carboplatin
Must have received at least one regimen containing gemcitabine chemotherapy
Adults with histologically proven solid tumor for which a PD-1 or a PD-L1 agent is indicated:\r\n* Non-small cell lung cancer who has failed at least 1 treatment regimen for metastatic or recurrent disease; patients must have received a prior platinum-containing regimen\r\n* Locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy\r\n* Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who had disease progression on or after platinum-containing chemotherapy or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy\r\n* Advanced renal cell carcinoma whose disease worsened during or after treatment with an anti-angiogenic agent\r\n* Unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor
Disease Status: 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:
Cytarabine containing regimen in excess of 2 g/m^2/day within 6 months of study entry
progression or relapse during or within 6 months of the most recent treatment with a platinum-containing chemotherapy regimen
Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at least 2 cycles). In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy, progression had to occur within 12 months of treatment.
Subject has experienced disease progression on or after platinum-containing chemotherapy
Previous therapy:\r\n* Patients must have progressed after standard therapy for metastatic/recurrent disease; this must have included irinotecan and oxaliplatin-containing regimens for patients with colorectal cancer (CRC) and platinum-containing regimens for patients with head and neck squamous cell carcinoma (H&NSCC)\r\n* Patients may have received cetuximab or panitumumab previously
Participants must have had at least one prior platinum-based chemotherapeutic regimen for management of primary disease (e.g., a regimen containing carboplatin, cisplatin, or another organoplatinum compound); this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment
Participants must have recurrence within 12 months of their last platinum-containing regimen
Prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds.
Known hypersensitivity to oxaliplatin, other platinum-containing compounds
Must have progression on or after therapy containing platinum/fluoropyrimidine or refused standard therapy.
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (biologic/targeted agents, such as bevacizumab) or extended therapy administered after surgical or non-surgical assessment; if patients were treated with paclitaxel for their primary disease, this can have been given weekly or every 3 weeks
Had disease progression while on a platinum containing regimen in the first-line setting or within 14 months after completing the first-line platinum regimen. Participants who received treatment with one immune checkpoint inhibitor regimen are eligible (for example PD-1, PDL1, or CTLA4) and may have a longer interval since prior platinum-containing therapy (?24 months).
Progression of disease based on imaging after the second-line platinum-based regimen (individuals treated with a pegylated liposomal doxorubicin-containing regimen as a second-line therapy are eligible if subsequent disease progression occurs >=9 months from the first dose)
Patients must have previously received a platinum and paclitaxel containing regimen
Has received prior therapy with at least 1 platinum-containing regimen
Prior therapy containing MMAE
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).
Known hypersensitivity to oxaliplatin or other platinum containing compounds
Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ? 12 months following completion of therapy.
Radiographic progression after treatment with at least 2 cycles of a platinum-containing doublet
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment
Previous treatment with CLAG or other chemotherapy regimen containing both cladribine and cytarabine
i) With at least 1 platinum-containing chemotherapy regimen for metastatic or surgically unresectable locally advanced urothelial cancer, or
Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet
Disease progression during or following treatment with at least one platinum-containing regimen for inoperable, locally advanced or metastatic UBC or disease recurrence
Patients must have previously received, not tolerated, or been judged clinically unsuitable for platinum-containing therapy
Progression or recurrence of urothelial cancer following a first-line platinum-containing regimen (e.g cisplatin, carboplatin) for metastatic or inoperable locally advanced disease; or adjuvant platinum-based therapy following cystectomy for localized muscle-invasive urothelial cancer with recurrence/progression <=12 months following completion of therapy; or neoadjuvant platinum-containing therapy prior to cystectomy for localized muscle-invasive urothelial cancer with recurrence <=12 months following completion of therapy
Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence.
A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
For patients to be treated with a regimen containing 5-fluorouracil/leucovorin:
For patients to be treated with a regimen containing capecitabine:
For patients to be treated with a regimen containing oxaliplatin:
Known hypersensitivity to oxaliplatin or other platinum containing compounds
Previously treated with 1-3 lines of therapy (example: completed greater than or equal to [>/=] 2 treatment cycles per therapy), including at least one standard chemotherapy-containing regimen
For participants with the 17p deletion, previously treated with 1-3 lines of therapy, including at least one prior standard chemotherapy-containing regimen or at least one prior alemtuzumab-containing therapy
Patients who have completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation:
Patient has received at least one prior platinum-containing (cisplatin or carboplatin) regimen
a purine analog-containing regimen
a bendamustine-containing regimen
a chlorambucil-containing regimen
an alemtuzumab-containing regimen (for those subjects with a 17p deletion)
No prior chemotherapy, including carmustine-containing wafers (Gliadel®)
Stage IV locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy or had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Expanded Safety Cohort participants must have confirmed metastatic lung cancer and progressed after receiving prior platinum-containing chemotherapy.
Patients must have had at least one prior platinum/taxane combination chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatin compound; this initial treatment may include intraperitoneal therapy, high dose therapy, consolidation, noncytotoxic agents, or extended therapy
Recurrent or refractory disease after receiving at least one prior standard/approved platinum-containing chemotherapy regimen, or where standard therapy is refused. Part 2 only: Subjects must have recurrent disease after receiving a maximum of two prior chemotherapy regimens including at least one platinum containing regimen.
Progression on prior oxaliplatin-containing regimen used in 1st line setting for mCRC or progression within 6 months of end of oxaliplatin-containing regimen in the adjuvant setting.
Participants must have received 1 prior platinum-based chemotherapy regimen (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) disease followed by documented progressive disease (PD).
Prior therapy: patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organo-platinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (including anti-angiogenesis agents) or extended therapy (i.e. maintenance therapy) administered after surgical or non-surgical assessment; maintenance therapy should not be longer than 18 months duration
Porphyria or hypersensitivity to porphyrins (constituents of porfimer sodium), gemcitabine, cisplatin or other platinum-containing compounds
Patients must have received 1 prior platinum containing doublet regardless of mutation status
History of exposure to pseudomonas exotoxin containing molecule
Patients must have received prior platinum containing treatment.
Known allergy to eggs, gentamicin or platinum-containing compounds
Disease that has progressed or relapsed during or within 6 months after the most recent treatment with a platinum-containing chemotherapy regimen
Completed 1 line of chemotherapy treatment with a platinum-containing regimen in the advanced setting
Less than three weeks since the last chemotherapy-containing regimen
platinum-resistant cancer, defined as disease that responded to a platinum-containing chemotherapy regimen, but demonstrated recurrence within six months following the completion of that platinum-containing regimen, OR
Subject has experienced disease progression or unacceptable toxicity/intolerance after receiving at least 1 systemic platinum-containing regimen;
Prior systemic therapy with a gemcitabine containing regimen
Received at least 2 cycles of a bortezomib-containing regimen and 2 cycles of a lenalidomide-containing regimen, unless intolerant to these agents (defined as requiring discontinuation due to toxicity).
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.
Progression during or after treatment with a regimen that includes a platinum salt (e.g., carboplatin or cisplatin) OR
Must have had ? 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin or another organoplatinum compound for management of primary disease. This initial treatment may have included intraperitoneal (IP) therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment.
Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell Carcinomas should have a documented history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen
Documented progression of disease (locally recurrent or metastatic) per investigator assessment following first-line treatment with 4-6 cycles of Bevacizumab plus a platinum doublet-containing chemotherapy regimen and a minimum of 2 cycles of Bevacizumab (monotherapy) maintenance treatment prior to first progression of disease
Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
Prior treatment with an oxaliplatin-containing regimen
Disease-related criteria for Part 1 and Part 2: 1) Histologically or cytologically documented non-small cell lung cancer (NSCLC) - adenocarcinoma; 2) Stage III b or IV disease; 3) Tested for presence of echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement; 4) Received at least 2 prior lines of Food and Drug Administration (FDA)-approved systemic therapy, of which one therapy has to be a platinum-containing regimen OR failed or completed a first-line platinum-containing regimen and refused a second-line regimen despite being informed about the different therapeutic options and their specific clinical benefit by the investigator; the content of this informed consent discussion including the therapeutic options reviewed by the investigator needs to be documented and the subject needs to sign a specific consent form; Disease-related criteria for Cohort 2B only: 1) Mesothelin protein overexpression, defined by immunohistochemistry (IHC) as detection of the protein by greater than or equal (>=) 50 percent (%) of tumor cells on archived tumor material; 2) Primary tumor or metastatic lesion(s) amenable to tumor core biopsies
Participants who have used opioid-containing medications (including cough/cold medications containing codeine and/or antidiarrheals containing loperamide) in the past 2 weeks, or who are expected to require opioid-containing medications within the duration of the treatment period
Any prior chemotherapy is allowed including prior treatment with platinum-containing chemotherapy
STEP I: Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking lenalidomide and for 28 days after stopping lenalidomide; male subjects must also agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from lenalidomide; male subjects must be willing to use condoms for 90 days after discontinuation of carfilzomib
STEP II: Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking lenalidomide and for 28 days after stopping lenalidomide; male subjects must also agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from lenalidomide; males must agree to use contraception and agree to not donate sperm for at least 90 days after the last day of carfilzomib
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
Lenalidomide: 7 days
Received >6 cycles lifetime exposure to Lenalidomide.
Received 2-4 prior lines of therapy, including lenalidomide and a PI, either sequential or in the same line, and is refractory (relapsed and refractory or refractory) to lenalidomide in the last line. Refractory status to lenalidomide is defined as progression while on lenalidomide therapy or within 60 days of last dose, following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per cycle.
Patients with 5q del MDS unless failed on Revlimid (lenalidomide)
ARM 3: Must have had at least 1 but no more than 3 prior lines of anti-myeloma therapy; exposure to carfilzomib and lenalidomide is allowed but must not be refractory to either drug; must be 6 months from prior therapeutic lenalidomide (> 4 weeks if lenalidomide used as maintenance [dose < 15 mg]) and ?8 weeks from prior carfilzomib
All subjects must have failed 1+ prior treatment, one of which must include lenalidomide therapy\r\n* Patients requiring second (2nd) line of therapy must meet criteria of lenalidomide-refractory disease defined as a history of progression on or within 60 days of completion of a regimen of a minimum of 2 cycles containing full or maximally tolerated dose of lenalidomide\r\n** Patients progressing on lenalidomide maintenance in the first line of therapy will be eligible provided that they have received at least 2 cycles of lenalidomide at established standard maintenance dosing schedule; maintenance dosing and schedule must be documented and approved by lead principal investigator prior to enrollment \r\n* For patients requiring third (3rd) or higher line of therapy, history of treatment with lenalidomide is required but lenalidomide-refractory status is not\r\n* In addition, subjects also refractory to pomalidomide, carfilzomib, or bortezomib are permitted limited to 10 subjects per group
Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
Patients with 5q- syndrome should have failed to respond to or progressed on treatment with lenalidomide, where available and indicated
Women of childbearing potential and sexually active males must agree to use 2 methods of an accepted and effective method of contraception and counseled on the potential teratogenic effects of lenalidomide; effective contraception must be used by patients for at least 4 weeks before beginning lenalidomide therapy, during lenalidomide therapy, during dose interruptions and for 4 weeks following discontinuation of lenalidomide therapy; reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or because the patient has been postmenopausal naturally for at least 24 consecutive months; two reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is the chosen method; females of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed; sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be females of childbearing potential; it is not known whether CC-5013 (lenalidomide) is present in the semen of patients receiving the drug; therefore, males receiving CC-5013 (lenalidomide) must always use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy
Patients must not have received prior therapy with lenalidomide (for more than 2 months) nor eltrombopag
Able to take aspirin (81 or 325 mg) daily or for thromboprophylaxis with lenalidomide.
Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
Prior therapy with lenalidomide
Patients who previously received lenalidomide and have experienced toxicities resulting in treatment discontinuation.
Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
Patients who previously had any intolerance to lenalidomide 10 mg or who have a contraindication to lenalidomide will not be eligible for concomitant treatment with lenalidomide but will remain eligible for CAR T cell therapy without lenalidomide
Has progressed on prior therapy with lenalidomide
Prior venetoclax or other BCL-2 family inhibitors or prior lenalidomide is not permitted
Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy\r\n* Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids and/or lenalidomide and/or bortezomib/principal investigator (PI)-based regimens does not disqualify the subject (the corticosteroid treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle of lenalidomide and/or PI-based therapy)
Currently using lenalidomide or hypomethylating agents (HMA)
Breast feeding (if lactating, must agree not to breast feed while taking lenalidomide); breastfeeding should be discontinued if the mother is treated with lenalidomide
Subject has received > 6 months of lenalidomide (Revlimid) therapy prior to stem cell collection
Prior lenalidomide exposure is permitted only if the subject did not discontinue lenalidomide due to a related, grade >= 3 adverse event (AE)
Patients with history prior to transplant of progression on lenalidomide therapy
Failed 2 or more prior standard MM therapies, and >100 days post autologous bone marrow transplant prior to first dose for transplanted subjects. Prior lenalidomide is permitted.
History of hypersensitivity to lenalidomide (Part B only)
Patients who completed induction treatment followed by autologous stem cell transplant as initial therapy for symptomatic myeloma as per IMWG criteria and are considered for single agent lenalidomide (Revlimid) maintenance or initiated single agent Revlimid maintenance\r\n* Patients will be eligible for enrollment in the first 0-4 months of lenalidomide maintenance provided that lenalidomide maintenance has been initiated on days 60 - 120 after transplant\r\n* Patients must be receiving lenalidomide 10 mg or 15 mg and be able to tolerate dose escalation to 25 mg daily\r\n* Patients receiving lenalidomide maintenance cannot exceed 4 months of lenalidomide post-transplant
Previous treatment with lenalidomide for AML
All patients must have received prior lenalidomide therapy and been determined to be refractory; refractory will be defined as a history of progression on a regimen containing full or maximally tolerated dose of lenalidomide administered for a minimum of at least two completed cycles of therapy
Prior to enrollment, sites must provide evidence of myeloma progression/relapse and evidence of being refractory to lenalidomide, with start and stop dates of lenalidomide therapy and the most recent treatment regimen, as well as best tumor response to all prior treatment regimens
Any prior use of lenalidomide.
Has received at least 2 consecutive cycles of lenalidomide and be refractory to lenalidomide, as defined per protocol.
Previously treated relapsed and refractory multiple myeloma\r\n* Patients must have received at least one prior line of therapy\r\n* Prior therapy must include at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)\r\n* Patients must be refractory and/or relapsed/refractory to lenalidomide or prior lenalidomide\r\n* Disease progression on or within 60 days of completion of last therapy
Patients must be lenalidomide failures: disease progression on a prior lenalidomide-based therapy or progression within 60 days of the last dose of a lenalidomide; patients should have received at least 2 cycles of a lenalidomide-based regimen at standard doses to be evaluable for refractoriness; prior intolerance to lenalidomide does not exclude participation in the study except in cases of severe allergic reaction
Patient must agree to take lenalidomide with low dose dexamethasone as their initial therapy
Subject must be at least 2 months (from first dose of lenalidomide) from stem cell infusion.
Subject has isolated Central Nervous System (CNS) involvement or extramedullary relapse. (Subjects with combined CNS/marrow relapse may be Subject has had prior treatment with cytotoxic chemotherapy within 2 weeks of the first dose of lenalidomide with the exception of hydroxyurea (allowed prior to the first dose of lenalidomide and through Day 14 of Cycle 1) and intrathecal (IT) cytarabine will be administered within 2 weeks prior to administration of lenalidomide.
Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide ( for lenalidomide : unless the last dose received is >= 8 weeks prior to inclusion into the study).
? 2 prior lines of therapy which must have included at least 2 consecutive cycles of lenalidomide and a proteosome inhibitor alone or in combination
Refractory to proteosome inhibitor and lenalidomide, and to last treatment
Patients must not have prior therapy with lenalidomide
Patients must have completed 16 weeks of monotherapy with lenalidomide
Patients must not have a limiting unresolved grade 3 or greater toxicity from lenalidomide monotherapy or drug intolerance preventing continuation of lenalidomide treatment
Agreement to comply with all local requirements of the lenalidomide risk minimization plan
History of resistance to lenalidomide or response duration of <1 year
Patients may have received prior lenalidomide as long as it has been at least two years since exposure and the patient may not have experienced a progression while receiving lenalidomide previously
Prior therapy with lenalidomide
Prior treatment with lenalidomide
Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral lenalidomide
Patients must have also undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of a proteosome inhibitor (either in separate regimens or within the same regimen).
Any prior use of lenalidomide
Del(5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as either: 1) having received at least 3 months of lenalidomide treatment without RBC transfusion benefit (International Working Group [IWG] 2006); 2) progression or relapse after hematologic improvement with lenalidomide (IWG 2006); 3) discontinuation of lenalidomide due to toxicity; or 4) unable to receive lenalidomide due to a contraindication. Source documentation for lenalidomide treatment failure must be verified by the sponsor
Prior use of lenalidomide
If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment.
Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy.
Prior use of lenalidomide.
Pregnancy tests must occur within 10-14 days and again within 24 hours prior to initiation of cycle 1 of lenalidomide; females of childbearing potential (FCBP) with regular or no menstruation must have a pregnancy test weekly for the first 28 days and then every 28 days while on lenalidomide therapy (including breaks in therapy); at discontinuation of lenalidomide and at day 28 post the last dose of lenalidomide; females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 14 days while on lenalidomide therapy (including breaks in therapy), at discontinuation of lenalidomide and at day 14 and day 28 post the last dose of lenalidomide
Females of childbearing potential must have a negative serum pregnancy test with a minimum sensitivity of 50 mIU/mL and agree to use two medically accepted forms of contraception from the time of initial screening through completion of the study or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: \r\n* For at least 28 days before starting lenalidomide \r\n* Throughout the entire duration of lenalidomide treatment\r\n* During dose interruptions\r\n* For at least 28 days after lenalidomide discontinuation.
Prior use of lenalidomide if discontinued due to toxicity
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)
Patients must not have had progression of disease on lenalidomide 25 mg; stable disease on lenalidomide is permitted
Disease shows evidence of refractoriness or intolerance to lenalidomide or if previously treated with a lenalidomide-containing regimen the participant is excluded if he or she discontinued due to any adverse event related to prior lenalidomide treatment
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)
Prior use of lenalidomide if discontinued due to toxicity
History of hypersensitivity to lenalidomide
Patients who are post auto-SCT as primary therapy must have received maintenance therapy with lenalidomide
Patients must be registered within 6 months of last dose of lenalidomide
All subjects must have received prior treatment with a lenalidomide containing regimen for at least 2 consecutive cycles.
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
Calculated creatinine clearance ? 30 mL/min NOTE: Participants with a low creatinine clearance ? 60 mL/min (or ? 50 mL/min, according to lenalidomide prescribing information/local practice) were to receive a reduced lenalidomide dose of 10 mg once daily (QD) on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may have been escalated to 15 mg QD after 2 cycles if the participant was not responding to treatment and was tolerating the treatment. If renal function normalized (ie, creatinine clearance >60 mL/min or >50 mL/min, according to lenalidomide prescribing information/local practice) and the participant continued to tolerate this treatment, lenalidomide may then have been escalated to 25 mg QD.
Any prior use of lenalidomide
Any prior use of lenalidomide.
Patients may have received lenalidomide and/or dexamethasone
Prior treatment with Lenalidomide permitted if:
Subject did not receive more than 9 cycles of Lenalidomide and had at least 9 months between the last dose of Lenalidomide and progression
Patient has any prior use of lenalidomide
Patients with MDS should have failed prior therapy with a hypomethylating agent or, if associated with a 5q- chromosomal abnormality, lenalidomide. NOTE: Patients with 5q- unable to receive or intolerant to lenalidomide are also eligible.
History of intolerance or resistance to lenalidomide
Any prior use of lenalidomide
Active infection at the start of lenalidomide
Must agree to receive counseling related to teratogenic and other risks of lenalidomide.
Prior therapy with lenalidomide.
Prior therapy with lenalidomide.
Received prior treatment for MDS with lenalidomide or hypomethylating agents (HMAs).
Treatment with investigational GVHD prophylactic agents (eg, CCR5 inhibitors; lenalidomide; and/or bortezomib) within the 7 days prior to the 1st dose of neihulizumab
ELIGIBILITY FOR VACCINE AND LENALIDOMIDE ADMINISTRATION (PROTOCOL ENTRY)
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
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.
Patients must have received previous bortezomib-containing and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available)
Lenalidomide must have been used for at least 6 months after autologous hematopoietic stem cell transplantation with the current dose of lenalidomide 15 mg/day or less
Relapsed myeloma that previously became refractory to lenalidomide, after initial response of partial response or better to the drug; refractory is defined as progression on treatment with a dose of at least 10 mg daily for lenalidomide; greater than or equal to 180 days must have elapsed since previous lenalidomide therapy was stopped
Prior treatment with lenalidomide
Patients must be suitable for treatment or re-treatment with lenalidomide & dexamethasone; Note: patients previously treated with lenalidomide & dexamethasone are eligible to participate in the trial
All patients must agree to follow the requirements for lenalidomide counseling, pregnancy testing and birth control; for women of childbearing potential (WOCBP) this includes pregnancy testing prior to prescribing lenalidomide and to either commit to continued\r\nabstinence from heterosexual intercourse or begin acceptable methods of birth control for 28 days prior to prescribing lenalidomide, during therapy and for 28 days after the last dose of lenalidomide; WOCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a WOCBP even if they have had a successful vasectomy and must agree not to donate semen during study drug therapy and for a period of time after therapy; all patients must abstain from donating blood, agree not to share lenalidomide with others and be counseled about the risks of lenalidomide
Prior Lenalidomide exposure is permitted only if the subject did not discontinue Lenalidomide due to a Grade ?3 related Adverse Event (AE)
All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib
All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [? partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ? minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
Prior treatment with lenalidomide or everolimus
Discontinuation of previous lenalidomide or dexamethasone due to intolerance; subjects intolerant to bortezomib are not excluded
Subjects must agree to receive counseling related to pregnancy precautions, teratogenic and other risks of lenalidomide
Prior lenalidomide therapy.
Patients must be suitable for treatment with lenalidomide & dexamethasone.
Both men and women in the lenalidomide combination arm (Cohort D) must adhere to the guidelines of the RevAssist program (United States participants) or, if not using commercial supplies, must adhere to the Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Study Manual.
For participant in the lenalidomide combination arm, demonstrated hypersensitivity (example, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide.
Platelet count =< 50 x 10^9/L untransfused of at least 2 weeks duration, secondary to prior chemotherapy; if there is a platelet count of > or = 50 x 10^9/L after a transfusion, that value will be discounted; this may include a combination regimen including lenalidomide; these regimens will include dexamethasone, cyclophosphamide, etoposide, cisplatin (DCEP), Velcade with Doxil, Cytoxan and/or lenalidomide; patients who have thrombocytopenia (CIT) from lenalidomide or from radiation therapy alone will not be allowed; patients may be retreated with Nplate within 6 months of their initial response, with a different chemotherapy regimen
Patients receiving maintenance therapy with myelosuppressive medications such as lenalidomide will be excluded
Lenalidomide naïve; relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least one prior line of salvage therapy with no prior exposure to lenalidomide, or double-refractory FL subjects with no prior exposure to lenalidomide (FL-1 cohort)
Lenalidomide exposed: relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in combination
Recommended to start lenalidomide
Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or as the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
STEP II: Patients must have complete induction without experiencing progression or patients must have received at least 6 cycles on Arm A and 4 cycles on Arm B but stopped induction therapy due to adverse events
REGISTRATION STEP 2-RANDOMIZATION: Patients must be deemed, in the judgment of the treating physician, to be ineligible for intensive induction therapy, or must have refused intensive induction therapy; rationale for clinical determination or notation of patient decision must be made
Patients must have resolved any serious infectious complications related to induction
DS HR B-ALL patients with Induction failure or BCR-ABL1
DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
Patient may be receiving or have completed induction therapy within 60 days prior to preregistration to step 0; no more than 300 days may have passed between the first day of induction therapy and preregistration to step 0\r\n* For patients who have completed induction therapy, restaging evaluation must show status of partial (PR) or complete response (CR); post-induction patients with evidence of clinical disease progression are not eligible for preregistration\r\n* Up to two regimens of chemotherapy are allowed as long as a continuous response was ongoing throughout therapy; overall, a partial response needs to have been achieved (using studies at the time of diagnosis as the baseline)\r\n**NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to rituximab(R)-cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens; however, R-CHOP alternating with R-dexamethasone, high-dose cytarabine, and cisplatin (DHAP) as a planned induction regimen would count as one regimen
Patients must have completed induction therapy within 120 days prior to registration to step 1, AND no more than 300 days may have elapsed from the first dose of induction chemotherapy (cycle 1 [C1] day 1 [D1]) given, until the last day of induction chemotherapy administered; for those assigned to Arms A, C, or D, the date of transplant (“day 0”) must not be greater than 365 days after the first dose of induction chemotherapy (C1D1) given\r\n* Patient must have received at least four (4) cycles of induction therapy \r\n* Up to two regimens of chemotherapy are allowed as long as a continuous response was ongoing throughout therapy\r\n** NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to R-CHOP (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens; however, R-CHOP alternating with R-DHAP as a planned induction regimen would count as one regimen
Patients must be registered within 35 days of administration of the last dose of first-line/induction systemic therapy.
Patient must have previously started induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
Patient has not received more than 14 days of multiagent induction therapy beginning with the first dose of vinCRIStine
Completion of remission induction therapy
Registration Step 1 – Induction/Re-Induction:
For patients 65-69 years of age, patient must be deemed not suitable for standard intensive induction chemotherapy at the discretion of the local investigator, or must have refused standard intensive chemotherapy
COHORT 1 PH-NEGATIVE PATIENTS ONLY: Patients must have achieved CR or CRi within 2 cycles of induction/re-induction with blinatumomab\r\n* NOTE: day 1 of post-remission = day 43 of the preceding cycle (+/- 3 days)
COHORT 2 PH-POSITIVE AND PH-LIKE DSMKF PATIENTS ONLY: Newly diagnosed Ph+, newly-diagnosed Ph-like DSMKF, and relapsed/refractory Ph+ patients without prior dasatinib or other 2nd or 3rd generation TKI therapy, must have achieved CR or CRi within 1 cycle of induction with dasatinib/prednisone, or within 2 cycles of re-induction with blinatumomab; relapsed/refractory Ph+ or Ph-like DSMKF patients with prior dasatinib or other 2nd or 3rd generation TKI therapy must have achieved CR or CRi within 2 cycles of re-induction therapy with blinatumomab\r\n* NOTE: day 1 of post-remission = day 85 of the preceding induction cycle (+/- 3 days), or day 43 of the preceding re-induction cycle (+/- 3 days) as applicable
Eligible for standard induction chemotherapy according to their treating physician
Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
leukemia refractory to ? 2 induction attempts,
Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine
Treatment-naive participants unfit for induction chemotherapy for AML due to comorbidities who are >/=65 years old
1. Written informed consent must be obtained prior to any screening procedures\n\n          2. Male or female patients ? 18 years of age who present with one of the following:\n\n             Arms 1-3:\n\n               -  Refractory/relapsed AML following ?1 prior therapies and are deemed by the\n                  investigator not to be candidates for standard therapy, including re-induction\n                  with cytarabine or other established chemotherapy regimens for patients with AML\n                  (patients who are suitable for standard re-induction chemotherapy or\n                  hematopoietic stem cell transplantation and willing to receive it are excluded)\n\n               -  De novo AML patients who are suitable for treatment with decitabine (patients who\n                  are suitable for standard induction chemotherapy or hematopoietic stem cell\n                  transplantation and willing to receive it are excluded)\n\n               -  High risk MDS (patients who are suitable for standard re-induction chemotherapy\n                  or hematopoietic stem cell transplantation and willing to receive it are\n                  excluded)\n\n             Arms 4-5:\n\n               -  Refractory / relapsed AML following ?1 prior therapies (Arms 4a & 5a)\n\n               -  High risk MDS who have failed hypomethylating agent therapy (Arms 4b & 5b) (Note:\n                  hypomethylating agent failure is defined as progressive disease on\n                  hypomethylating agent therapy or lack of clinically meaningful response as deemed\n                  by investigator after at least 4 cycles of hypomethylating agent therapy.)\n\n          3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n          4. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to\n             the institutions guidelines and be willing to undergo a bone marrow aspirate\n             and/biopsy at screening, during and at the end of therapy on this study. Exceptions\n             may be considered after documented discussion with Novartis.\n\n          5. Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by\n             the investigator and as per local decitabine package insert.
COHORT 2: Is eligible for treatment with a standard cytarabine and anthracycline or similar intensive induction chemotherapy, or is willing to receive intensive induction therapy; if subject is not considered eligible for treatment with standard or similar intensive induction chemotherapy due to comorbidities or other factors, or is unwilling to receive intensive induction therapy will be allowed to participate in this study
Patients must be within 12 months of initiation of induction therapy and must have had not more than 2 prior induction regimens
Patients with AML refractory to primary induction chemotherapy, relapsed disease, or age >= 60 and not appropriate for standard cytotoxic therapy due to age, performance status, and/or adverse risk factors according to the treating physician
Previous treatment for MDS or AML with intensive chemotherapy regimen (induction chemotherapy) or hypomethylating agent
Acute myeloid leukemia\r\n* MRD > 5% at day 22 induction 1\r\n* MRD > 0.1% after induction 2\r\n* FMS-like tyrosine kinase (FLT)/internal tandem duplication (ITD) with allelic ratio > 0.4 and MRD > 0.1% at day 29 induction 1\r\n* Translocation (6:9), (8:6), (16:21), monosomy7, monosomy 5, 5q.\r\n* M7 without translocation (1;22)\r\n* M7 with KMT2A rearrangements, inv(16)(p13.3q24.3) [CBFA2T3-GLIS2] or t(11;12)(p15;p13) [NUP98-KDM5A]\r\n* AML in 2nd or subsequent CR\r\n* Therapy related or secondary AML\r\n* Refractory anemia with excess blasts (RAEB) 2
Participants must have pathologically confirmed relapsed or refractory acute myeloid leukemia following International Working Group (IWG) criteria\r\n* For subjects with relapsed AML: evidence of >= 5% blasts in the bone marrow or >= 5% blasts in peripheral blood or the development of extramedullary disease who relapse after:\r\n** Allogeneic hematopoietic stem cell transplant, or\r\n** A minimum of one cycle of standard cytotoxic chemotherapy or two cycles of any hypomethylating agent-based therapy\r\n* For subjects with refractory AML: a minimum of 2 prior induction regimens (example: patients who receive 7+3 followed by 5+2 would count as one induction regimen) or a minimum of two cycles of any hypomethylating agent-based therapy
Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside plus 2-3 days of an anthracycline, or high-dose cytarabine
Participant has not received more than 2 cycles of induction chemotherapy to achieve CR1. The induction cycles can be the same regimen or different regimens. The regimen(s) may contain conventional agents, investigational agents, or a combination of both.
Induction chemotherapy was administered with any combination of the following agents:
Patients may receive hydroxyurea or leukopheresis as necessary; hydroxyurea can be continued through induction, as determined by the treating investigator; patients who require hydroxyurea after the 2 induction cycles will be off study
Participants with leukemia must meet one of the following:\r\n* In first hematologic relapse, OR\r\n* Refractory to one or two courses of frontline induction therapy (>= 5% blasts in the bone marrow or peripheral blood confirmed by flow cytometric analysis)\r\n* Note: participants aged 1 to 5 years with induction failure and favorable cytogenetics (i.e., hyperdiploid or human ets variant 6 [ETV6]-runt-related transcription factor 1 [RUNX1]) will not be eligible for this protocol; other patients younger than 6 years will be eligible
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
ALL patient refractory to their first induction only or their first relapse, will be excluded; they must be refractory to at least one salvage therapy, or relapse after first salvage, to be eligible
Failure to one induction course of chemotherapy (these patients will be analyzed separately)
The time from the end of last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days
Patients who have been treated with chemotherapy or radiation for the purpose of induction, re-induction or consolidation, within two weeks of planned study enrollment
Any subject who is a candidate for intensive induction therapy and agrees to receive this therapy
Meet any criteria necessary for the safe and proper use of the induction and consolidation agents involved in this trial
Subjects unable or unwilling to have their first randomized treatment within three weeks of the post induction imaging and within five weeks of their last induction treatment
Patients must have a history of tumor progression or relapse or failure to achieve complete response following standard high-dose induction chemotherapy
Not considered eligible for any of the chemotherapy agents included in the induction regimen
Patients who have received induction chemotherapy for their cancer diagnosis.
Patients eligible for intensive induction chemotherapy and “medically unfit” based on a treatment related mortality (TRM) score >= 13.1\r\n* TRM score= a scoring model which predicts early death following intensive induction chemotherapy in newly diagnosed AML; \r\n** Model looks at ECOG performance status (PS), age, platelet count, albumin, second (2nd) AML, white blood cells (WBC), percentage (%) peripheral blasts, creatinine\r\n** Score above 13.1 associated with 31%+ chance of death after induction
Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:\r\n* Primary induction failure:\r\n** De Novo AML: No CR after 2, 3 or 4 induction attempts with high dose chemotherapy\r\n** Secondary AML (from myelodysplastic syndrome [MDS] or treatment related): No CR after 1, 2 or 3 cycles of high dose chemotherapy\r\n* Relapsed:\r\n** Not in CR after 1 or 2 cycles of standard re-induction therapy\r\n*** For patients > 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required
Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:\r\n* Primary induction failure:\r\n** De novo - no CR after 2 or more induction attempts with high dose chemotherapy\r\n** Secondary AML (from myelodysplastic syndrome [MDS] or treatment related): no CR after 1 or more cycles of high dose chemotherapy\r\n** Note: hypomethylating agents such as azacitidine will count as induction failure\r\n* Relapsed: not in CR after 1 or more cycles of standard re-induction therapy - patients > 60 years of age, the 1 cycle of standard chemotherapy is not required\r\n* Relapsed > 18 months after transplant: no re-induction required and no more than 1 re-induction cycle is allowed
Patients must be either refractory to or relapsed after only induction therapy; patients who do not achieve CR after induction therapy are considered primary refractory and are allowed to enter study
Patients will have received at least 2 cycles of induction chemotherapy with pemetrexed/cisplatin or pemetrexed/carboplatin
Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one cycle of re-induction therapy; standard dose 10-day decitabine (20 mg/m^2 daily IV x 10 days) or 7-day azacitidine (75-100 mg/m^2 daily SC/IV x 7 days) will be considered as one cycle of induction therapy
Has undergone cytotoxic induction therapy
Relapsed or refractory high-grade myeloid neoplasms, defined as having a blast count of >= 10% blasts at initial diagnosis; examples include excess blasts (EB)-2, with >= 10% blasts at initial diagnosis, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML-2); standard definitions of relapse will apply (i.e., characterized by >= 5% abnormal blasts as assessed by multiparameter flow cytometry or morphologic examination; peripheral blood blasts; or extramedullary granulocytic sarcoma, per European LeukemiaNet [ELN] 2017 guidelines); bone marrow aspirate/biopsy will be accepted if performed outside University of Washington/Fred Hutchinson Cancer Research Center (UW/FHCRC); determination of disease status should occur within 30 days of signing informed consent\r\n* R/R high-grade myeloid neoplasm following intensive induction chemotherapy; relapsed high-grade myeloid neoplasm: patients will be classified as relapsed if they have >= 5% blasts after being in a complete remission (CR) following treatment for high-grade myeloid neoplasm; refractory high-grade myeloid neoplasm: patients may be classified as refractory if they have received at least one prior cycle of induction chemotherapy, whether with cladribine cytarabine mitoxantrone (GCLAM) or another regimen\r\n** Patients may have received up to two courses of intensive induction chemotherapy during initial treatment prior to enrollment on this protocol; for example, patients who have received two courses of granulocyte colony stimulating factor (G-CSF) GCLAM (or similar) chemotherapy, with most recent high-dose cytarabine-containing chemotherapy > 6 months ago and CR lasting > 6 months, will be eligible for this protocol; regimens “similar to GCLAM” would include cytarabine at doses of 1g/m^2 for at least 5 doses; examples of regimens “similar to GCLAM” would be GCLA, fludarabine cytarabine granulocyte (FLAG), and FLAG-idarubicin (ida); however, patients who received more than two courses of GCLAM (or similar) chemotherapy, or patients who received two courses of GCLAM and had CR lasting < 6 months, would not be eligible\r\n* R/R high-grade myeloid neoplasm following less intensive induction chemotherapy. Patients who have received at least three cycles of treatment with a hypomethylating agent (HMA; such as azacitidine or decitabine) and still have >= 10% blasts will be eligible for the study (they will be considered refractory); similarly, patients who have received three or more cycles of HMA therapy who have had a response (e.g., achieving CR with < 5% blasts), but who then progress using standard definitions of relapse, will also be eligible (they will be considered relapsed)
More than two prior courses of induction chemotherapy
Have received the last dose of induction or consolidation chemotherapy within 3 months of enrollment
Patient must have completed a frontline induction therapy (minimum of 2 treatment cycles); NOTE: Standard therapies/therapeutic agents are defined as those listed in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of CLL; also, patients who received induction regimen as part of a clinical trial and is not necessarily mentioned in the NCCN guidelines, will also be eligible as long as the patient has completed at least 2 treatment cycles of induction regimen, achieved a clinical response (PR or CR) and is able to meet all other criteria for the study; however, patients who have previously received ibrutinib or have been randomized to ibrutinib containing arms in a clinical trial will not be eligible for this study
Have received induction chemotherapy and at least one cycle of consolidation chemotherapy; patients should have achieved a CR within 12 months of enrollment onto protocol
Patients with diagnosis of AML, judged primary refractory after up to 2 courses of AML induction with therapy (> 5% blasts on day 21 [+/-7 days] bone marrow aspirate and/or biopsy from the beginning of induction chemotherapy, up to 42 days)
Prior induction therapy with decitabine, clofarabine, idarubicin (DAC) + cytarabine (CIA)
Patients must meet one of the following criteria:\r\n* The presence of refractory or progressive disease (PD) prior to or following completion of standard therapy for MIBG avid tumors\r\n* For patients with neuroblastoma, the presence of mixed response (MR), or no response (NR) following the completion of A3973 or equivalent induction therapy, or the presence of a partial response (PR) with high Curie score (> 2) following induction therapy \r\n* Patients with de novo high risk neuroblastoma who have completed standard induction therapy and do not achieve a complete response (CR), very good partial response (VGPR), or PR with low Curie score post induction are eligible; for patients with neuroblastoma the revised International Neuroblastoma Response Criteria (INRC) shall be used to assess pre-treatment disease status
Recipients with acute lymphoblastic leukemia (ALL) in CR1 must have one of the following:\r\n* Adverse cytogenetics defined as translocations involving t(4;11), t(1;19), t(8;14), 11q23, t(9;22) or bcr-abl rearrangement or complex cytogenetic abnormalities\r\n* Presence of minimal residual disease using multicolor flow cytometry or other analytic technique after primary induction chemotherapy\r\n* Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy
Patients in their FIRST CR or CRi may be eligible for enrollment only if they have a high risk feature, including, but not limited to: adverse karyotype, fms-related tyrosine kinase 3 (FLT3) mutation, history of antecedent hematologic disorder (AHD), presence of dysplasia in the bone marrow, therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, or presence of persistent minimal residual disease (detected by cytogenetics, molecular markers, or flow cytometry) at any point after initial induction cycle; patients aged >= 18 years with AML who have achieved a SECOND CR or CRi within 12 months of enrollment and are not immediately candidates for allogeneic stem cell transplant are also eligible
Patients should have received induction chemotherapy for AML and at least 1 consolidation
Prior induction therapy had to include no more than two cycles of cytotoxic chemotherapy and at least one induction cycle must have consisted of an anthracycline or anthracenedione and cytarabine combination with a reasonable schedule/dose according to the discretion of the investigator
More than 2 cycles of prior induction therapy for AML
The time from the end last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days from planned start of study treatment; Note: Chemotherapy given within 14 days of planned study enrollment for the purpose of controlling counts is permitted
DIAGNOSIS REQUIREMENT FOR PHASE I PATIENTS: Refractory AML without complete remission (CR) after induction therapy (primary induction failure) or relapsed AML after obtaining a CR OR
Measurable disease prior to induction chemotherapy
Cohort B: patients who have received prior fludarabine , clofarabine or drugs known to target T cells not permitted; but prior standard induction with anthracyclines and cytarabine ALLOWED including after demethylating agents
Prior receipt of induction chemotherapy followed by referral for concurrent chemoradiation is allowed
Patients must have either (1) refractory or relapsed high-risk NB (including v-myc myelocytomatosis viral related oncogene [MYCN]-amplified stage 3/4/4S and MYCN-nonamplified stage 4 in patients greater than 18 months of age) resistant to standard therapy, or (2) refractory or relapsed GD2-positive tumor after receiving available life-prolonging therapies\r\n* For NB, standard therapy generally includes 5-8 cycles of high dose induction chemotherapy followed by resection of gross residual tumor, then usually myeloablative chemotherapy with peripheral blood stem cell rescue and radiation therapy to the primary site; there are also salvage chemotherapy regimens for residual disease after standard induction therapy or for relapsed NB; some examples of these chemotherapy combinations are: high-dose cyclophosphamide, topotecan and vincristine; high-dose cyclophosphamide, irinotecan and vincristine; irinotecan and temozolomide; or ifosfamide, carboplatin and etoposide
Subjects with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
Be in first relapse (within 24 months of CR) or have primary refractory AML (refractory to initial induction therapy using 1 or 2 cycles of intensive anthracycline/cytarabine ± etoposide or cladribine induction) or have newly diagnosed high-risk AML as defined in this protocol.
Group A : Individuals > 18 years of age with previously untreated AML who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician
CR or PR required; remission status will be assessed at the completion of induction chemotherapy and prior to enrollment on protocol
Up to one cycle of prior induction therapy will be permitted to include patients in whom presence of \good-risk\ cytogenetics was initially missed; if the patient is in remission from induction therapy, he/she will receive post-remission therapy; if the patient is not in remission then he/she will receive induction therapy
At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy or azacitidine or decitabine or tyrosine kinase inhibitor
Refractory leukemia or MDS; these patients may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody; these high risk patients will be analyzed separately (Arm 3)
B-cell cohort: Stage 1; ALL in second or greater relapse or refractory to 2 prior induction regimens with greater than or equal to (>=) 5 percent (%) blasts in the bone marrow and aged 1 to less than (<) 18 years. Stage 2; ALL in second or greater relapse or refractory to 2 prior induction regimens with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in second or greater relapse or refractory to 2 prior induction regimens and biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years.
T-cell cohort: Stage 1; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to <18 years. Stage 2; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in first relapse or refractory to 1 prior induction/consolidation regimen biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years
Inclusion Criteria:\n\n        2.3.1 Inclusion Criteria for the Biology (KIR2DL1 Polymorphisms/ALL MRD), Comparative\n        Outcomes, and Cost Effectiveness Trial\n\n          1. Any patient with ALL, AML, or MDS who is deemed eligible for and undergoes HCT at\n             participating centers who provides consent for the KIR2DL1 polymorphisms, comparative\n             outcomes and cost-effectiveness portion of the trial.\n\n          2. Any ALL patient undergoing allogeneic HCT at participating centers is eligible for the\n             ALL deep sequence MRD portion of the trial.\n\n          3. Patients ineligible for the KIR-favorable haploidentical phase II trial who require\n             T-cell depletion may be treated using TCR ??+CD3+/CD19+ cell depletion. These patients\n             will be followed descriptively on this portion of the trial. Preparative regimen will\n             be at the discretion of the transplant center, but the options associated with this\n             protocol are recommended.\n\n        2.3.2 Inclusion Criteria for the KIR-favorable Haploidentical Phase II trial:\n\n          1. Age < 22 years\n\n          2. Disease and disease status:\n\n               -  ALL high-risk in first remission (<5% blasts by morphology pre-transplant)\n                  meeting criteria for transplant. Example CR1 indications: induction failure (>5%\n                  blasts by morphology on post-induction BM), minimal residual disease greater than\n                  or equal to 1% marrow blasts by morphology after induction, minimal residual\n                  disease by flow cytometry >0.01% after consolidation, hypodiploidy (<44\n                  chromosomes), persistent or recurrent cytogenetic or molecular evidence of\n                  disease during therapy requiring additional therapy after induction to achieve\n                  remission (e.g. persistent molecular BCR-ABL positivity).\n\n               -  ALL in second remission: B-cell; early (less than or equal to 36 months from\n                  initiation of therapy) BM relapse, late BM relapse with MRD >0.1% by flow\n                  cytometry after first induction therapy; T-cell or Ph+ with BM relapse at any\n                  time; very early (less than 18 months from initiation of therapy) isolated\n                  extramedullary relapse (T or B-cell)\n\n               -  Myelodysplastic syndrome (MDS): Any 2001 WHO classification subtype (Appendix I).\n                  RAEB-2 patients may proceed directly to transplant, but may also receive\n                  induction chemotherapy before transplant. Patients with ?20% morphologic marrow\n                  blasts will require induction therapy to reduce morphologic marrow blasts below\n                  5% before transplant.\n\n               -  High-risk AML defined as monosomy 5, del 5q, monosomy 7, M6, M7, t(6;9),\n                  FLT3-ITD, or patients who have greater than or equal to 25% blasts by morphology\n                  after induction, or who do not achieve CR after 2 courses of therapy. Also,\n                  patients with ? 0.1% MRD or evidence of progressive extramedullary disease after\n                  induction chemotherapy.\n\n               -  AML in second or subsequent morphologic remission.\n\n          3. Has not received a prior allogeneic hematopoietic stem cell transplant.\n\n          4. Does not have a suitable HLA-matched sibling donor available for stem cell donation.\n\n          5. Does not have a suitable matched or single antigen mismatched related or unrelated\n             donor available at any time (noted by search), or it is in the patient's best interest\n             as judged by the attending to move forward with stem cell transplantation rather than\n             wait for an unrelated donor to become available (refer to subsection 2.5.1 for further\n             details).\n\n          6. Has a suitable HLA KIR favorable haploidentical matched family member available for\n             stem cell donation.\n\n          7. Karnofsky Index or Lansky Play-Performance Scale ? 60 % on pre-transplant evaluation.\n             Karnofsky scores must be used for patients > 16 years of age and Lansky scores for\n             patients < 16 years of age.\n\n          8. Able to give informed consent if > 18 years, or with a legal guardian capable of\n             giving informed consent if < 18 years.\n\n          9. Adequate organ function (within 4 weeks of initiation of preparative regimen), defined\n             as:\n\n               -  Pulmonary: FEV1, FVC, and corrected DLCO must all be ? 50% of predicted by\n                  pulmonary function tests (PFTs). For children who are unable to perform for PFTs\n                  due to age, the criteria are: no evidence of dyspnea at rest and no need for\n                  supplemental oxygen.\n\n               -  Renal: Creatinine clearance or radioisotope GFR ³ 70 mL/min/1.73 m2 or a serum\n                  creatinine based on age/gender as follows:\n\n        Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8\n        0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4\n\n        ? 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the\n        Schwartz formula for estimating GFR utilizing child length and stature data published by\n        the CDC.45\n\n          -  Cardiac: Shortening fraction of ? 27% by echocardiogram or radionuclide scan (MUGA) or\n             ejection fraction of ? 50% by echocardiogram or radionuclide scan (MUGA), choice of\n             test according to local standard of care.\n\n          -  Hepatic: \\SGOT (AST) or SGPT (ALT) < 5 x upper limit of normal (ULN) for age.\n             Conjugated bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome.\n\n        Exclusion Criteria:\n\n          1. Pregnant or lactating females are ineligible as many of the medications used in this\n             protocol could be harmful to unborn children and infants.\n\n          2. Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded.\n             Patients with history of fungal disease during induction therapy may proceed if they\n             have a significant response to antifungal therapy with no or minimal evidence of\n             disease remaining by CT evaluation.\n\n          3. Patients with active CNS leukemia or any other active site of extramedullary disease\n             at the time of enrollment are not permitted. Note: Those with prior history of CNS or\n             extramedullary disease, but with no active disease at the time of pre-transplant\n             workup, are eligible.\n\n          4. Patients with genetic disorders (generally marrow failure syndromes) prone to\n             secondary AML/ALL with known poor outcome are not eligible (Fanconi Anemia, Kostmann\n             Syndrome, Dyskeratosis Congenita, etc).
ECOG performance status within 48 hours prior to induction chemotherapy ? 3
Must be within 3 months from the last induction regimen at the time of starting cytarabine chemotherapy in this protocol
In Cohorts A3 and A4 only, participants with AML eligible for standard intensive induction therapy with an anthracycline and cytarabine
Patients must be > 28 days from the start of induction or re-induction chemotherapy, or from the start of consolidation cycle 1 (if received) and < 90 days following recovery from most recent treatment; and they must have achieved and maintained a response to induction therapy (CR, CRi, or “morphologic disease-free state”)
Patients must have recovered from the effects of induction, re-induction, or consolidation chemotherapy (all toxicities =< grade I with the exception of reversible electrolyte abnormalities), and have no ongoing active infection requiring treatment
Patient with and without Down syndrome are eligible and must have one of the following:\r\n* Second or greater relapse;\r\n* Primary refractory disease with at least 2 prior induction attempts;\r\n* First relapse refractory to at least one prior re-induction attempt\r\n* Any relapse after HSCT\r\n* First relapse with no prior re-induction attempt in setting of Down syndrome\r\n* Note: Patients with Down syndrome are eligible with any disease status including first relapse with no prior re-induction attempt; patients without Down syndrome are NOT eligible if in first relapse with no prior re-induction attempt
Refractory to at least 1 cycle of induction chemotherapy
Patients with untreated AML who are either unwilling or unable to undergo high-dose induction/consolidation intensive chemotherapy
Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:\r\n* Non-M3 AML refractory to standard primary induction therapy \r\n* Non-M3 AML relapsed after (i) any standard induction therapy (ii) any number of standard or experimental salvage therapies\r\n* Newly diagnosed non-M3 AML not eligible for intensive induction chemotherapy
Subjects who are suitable for and willing to receive standard intensive induction therapy
To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016) \r\n* Relapsed patients\r\n** Patients must be in first relapse, and\r\n** Patients must not have received prior re-induction therapy\r\n* Refractory patients\r\n** Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example\r\n* Treatment-related AML (t-AML)\r\n** Patients must be previously untreated for secondary AML
To be eligible for the phase 2 efficacy phase:\r\n* Relapse patients:\r\n** Patients must be in first marrow relapse, and \r\n** Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody
Meets ONE of the following disease criteria:\r\n* Primary (de novo) AML induction failure: no CR after 2 or more induction attempts with high dose chemotherapy (note: hypomethylating agents such as azacitidine will count as induction failure)\r\n* Relapsed AML or secondary AML (from myelodysplastic syndrome [MDS] or treatment related): not in CR after 1 or more cycles of standard re-induction therapy\r\n** For patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:\r\n*** Relapse within 6 months of last chemotherapy\r\n*** Bone marrow (BM) blast count < 30% within 10 days of starting protocol therapy\r\n* AML relapsed > 4 months after transplant: no re-induction required, and no more than 1 re-induction cycle is allowed\r\n* Use of hydroxyurea is permitted to control blasts counts\r\n* Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
ALL or AML patients who received chemotherapy (induction or consolidation) can proceed to transplant once bone marrow cellularity is > 10 % with no evidence of leukemia
Please note: prior intensive induction therapy for acute leukemia is allowed only in the phase I portion of this study\r\n* PHASE I PORTION ONLY: Patients of any age who have received no more than one prior attempt at induction chemotherapy (and may have received treatment consolidation), must have recovered from acute toxicities of therapy and be >= 4 weeks from last dose of cytotoxic treatment; patients who have received prior autologous or allogeneic stem cell transplantation are not eligible; patients may have received 1 or 2 cycles of cytarabine-based therapy as attempted induction
Phase II portion: Patients must have not received any prior intensive induction therapy for AML\r\n* Intensive induction includes standard induction chemotherapy such as 7 & 3, high dose cytarabine, mitoxantrone-etoposide, low-dose subcutaneous cytarabine\r\n* Allowed \non-intensive\ prior treatments for pre-existing hematologic conditions (i.e., MDS, chronic myelomonocytic leukemia [CMML]) will include: hydroxyurea, thalidomide, hematopoietic growth factors, Zarnestra, Lenalidomide, arsenic, Imatinib, and corticosteroids, suberoylanilide hydroxamic acid [SAHA] inhibitors; hydroxyurea is allowed up to 24 hours before initiating treatment and to control blood counts during the first cycle of chemotherapy after azacitidine has completed; a minimum of 4 weeks must have elapsed since the administration of thalidomide, Zarnestra, Revlimid, arsenic, SAHA inhibitors, or any investigational medication; a minimum of five days must have elapsed since the administration of growth factors
Subject has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation, and/or maintenance).
In first relapse (with duration of remission of 6 months or less) or refractory after prior therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone-containing induction block at a standard dose.
The previous induction regimen may have been a SCT with intent to induce a CR.
The previous induction regimen may have been a SCT with intent to induce a CR.
INDUCTION ELIGIBILITY:
Patients must be registered to Consolidation therapy within 60 days of beginning Induction therapy (with day 1 being the start of Induction)
Patients must be in morphologic complete response (CR), complete response with incomplete hematologic recovery (CRi), partial response (PR) by international working group criteria post induction therapy, or patients refractory to induction therapy provided they have < 1000 peripheral blasts/mm^3 and white blood cells (WBC) =< 10 x 10^9/L; patients in PR and/or those who are refractory and who have undergone only one course of induction therapy will be eligible only if one or more of the following criteria are met:\r\n* Patient preference to forgo further induction therapy in favor of low or intermediate-intensity therapy\r\n* Patients are deemed unlikely to benefit from anthracycline cytarabine induction therapies for any of the following reasons:\r\n** Therapy-related AML\r\n** Prior myelodysplastic syndrome or myeloproliferative neoplasm\r\n** The presence of cytogenetic or molecular genetic features place patient in the Intermediate-I, Intermediate-II or adverse genetic group as defined by the European LeukemiaNet\r\n* Patients who have experienced one or more Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 grade 3-4 treatment related non-hematologic toxicity within 30 days of beginning the first course of induction therapy
Previous administration of > 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
Tumor progression during or immediately after completion of =< 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
Patients must have primary refractory ALL based on failure to achieve a hematologic or molecular remission after induction therapy with dasatinib and steroids or dasatinib and chemotherapy, or have relapsed after treatment with a tyrosine kinase inhibitor with or without chemotherapy\r\n* Note: Prior course of dasatinib and steroid induction therapy should have included dasatinib 140mg PO daily on days 1-84 and prednisone 60mg/m^2 (capped at 120mg, or equivalent steroid dose) on days 1-28; if patients were unable to tolerate full steroid dose during induction therapy they will still be eligible\r\n* Note: Patients with refractory or relapsed disease in the central nervous system will be eligible
Unfit for chemotherapy based on investigator assessment or patient not willing to receive intensive induction as advised by investigator
Any cancer directed therapies between completion of induction chemotherapy and treatment on protocol
Patients who have received induction chemotherapy for their cancer diagnosis
No induction chemotherapy
Subject must have histological confirmation of AML and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
Underwent standard of care induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial.
Cytoreduction allowed: \r\n* Hydroxyurea, corticosteroids, leukapheresis can be used prior to start of induction chemotherapy\r\n* Cyclophosphamide up to dose 50-60 mg/kg is allowed for cytoreduction, but must be given at least 7+/- 2 days before start of induction chemotherapy
Patients who have had conventional intensive cytotoxic induction chemotherapy for treatment of specifically MDS or AML are excluded
Failing to achieve a CR from original diagnosis after at least 1 induction attempt
Completion of induction chemotherapy with a minimum of 4 and no more than 6 cycles of a platinum agent and etoposide within 8 weeks of trial initiation.
Phase 2: i. Participants with AML who are refractory to, or have relapsed after, initial treatment for their disease, with no more than one prior line of therapy, and are judged not to be candidates for re-induction therapy that includes hematopoietic cell transplantation. Participants who have received prior cytarabine or decitabine are not excluded. OR ii. Participants with newly diagnosed, untreated AML ineligible for, or who have refused, standard intensive induction therapy
Subjects who are refractory to initial induction or re-induction treatment
Subjects must have exhibited lack of CR or PR or progression within 6 months after the last dose of a chemotherapy induction regimen or RIT.
Re-Induction Criteria (if applicable):
Patients who have progressed on initial therapy will not be considered for re-induction treatment
Patients must demonstrate one of the following:\r\n* Relapse after first complete remission\r\n* Refractory to induction chemotherapy (for example, failure to respond to 1 or more cycles of daunorubicin and cytarabine) or to reinduction\r\n* Refractory to hypomethylating agents
Not considered eligible for one or more of the chemotherapy agents included in the induction regimen
Primary AML induction failure: no complete remission (CR) after 2 or more induction attempts
Acute myeloid leukemia (AML) fitting within one of the following disease groups:\r\n* Primary induction failure (PIF): patients who have not achieved a complete remission (CR) after two induction cycles of cytotoxic therapy (i.e. 7+3, mitoxantrone, etoposide, and cytarabine [MEC], fludarabine, cytarabine, and granulocyte-colony stimulating factor [FLAG], etc.) and having =< 10,000 absolute circulating blasts measured at least 21 days from prior therapy; hydroxyurea may be used to control blasts count; demethylating agents do not count as induction therapy; however early re-induction therapy based on residual disease on a day 14 bone marrow (BM) will count as a 2nd cycle\r\n* Relapsed disease with low disease burden: AML with =< 10,000 absolute circulating blasts; hydroxyurea may be used to control blasts count: no re-induction attempts are required, but a maximum of 2 re-induction attempts is allowed to be eligible\r\n* CR3 or greater: this will include CRp defined as CR without platelet recovery to 100,000/mcL\r\n* CR1 or CR2 with high risk features: includes therapy induced, prior myelodysplastic syndromes (MDS) or myeloproliferative disease (MPD), high risk cytogenetic or molecular phenotype with no available donor (sibling or unrelated adult)
Failure to one induction course of chemotherapy (these patients will be analyzed separately)
Patients must be within 30 days of completing induction therapy.
Able to receive intensive induction chemotherapy
Patients who have received induction chemotherapy before radiation treatment
Induction chemotherapy is allowed
Recipients with ALL in CR1 must have one of the following:\r\n* Adverse cytogenetics or residual disease detectable by flow cytometry, cytogenetic analysis, FISH, or PCR; adverse cytogenetics in ALL are defined as translocations involving t(4;11), t(1;19), t(8;14), 11q23, t(9;22) or bcr-abl rearrangement or complex cytogenetic abnormalities\r\n* Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy
Refractory disease after first or greater relapse and a re-induction attempt, OR
Failing to go into remission from original diagnosis after 2 previous induction attempts.
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
Patients must have stable disease (or better) during the initial induction chemotherapy with first-line chemotherapy
Patient must start maintenance therapy at least 14 days after the last administered induction chemotherapy but no later than 30 days
Two or more relapses after initial response to induction chemotherapy
Patients should have received at least 2 cycles of induction therapy or 1 induction and 1 consolidation cycle, OR patient should be considered to have completed all planned chemotherapy, OR patient is considered to be unable, unfit or unwilling to receive additional chemotherapy
Previous treatment with hypomethylating agent or induction chemotherapy for MDS
Ability to undergo standard induction chemotherapy
Anti-neoplastic treatment less than 14 days prior to enrollment, with the exceptions of hydroxyurea or, in the case of a patient with primary refractory AML, prior induction chemotherapy
Patients who are not eligible for standard induction chemotherapy (or any standard therapy known to be life prolonging) because of poor performance status, significant tissue comorbidities, or unfavorable risk of disease
Patients eligible include those with diagnosis of AML other than acute promyelocytic leukemia by World Health Organization (WHO) criteria with relapsed disease after induction therapy or refractory to induction chemotherapy, as determined by morphology on bone marrow biopsy; also eligible are patients unwilling to receive standard induction chemotherapy
AML patients must either:\r\n* Be ineligible to receive standard intensive induction chemotherapy (based upon judgement of the treating physician, based on parameters such as comorbidities, cytogenetic studies as well as), or\r\n* Have relapsed or refractory disease to previous chemotherapy (induction and/or consolidation) for acute myeloid leukemia; patients must have recovered from acute toxicities of AML chemotherapy
INDUCTION CHEMOTHERAPY:
Patient must be sufficiently recovered from any adverse effect of induction chemotherapy as determined by treating investigator; the duration of this recovery period is anticipated to be 1-3 weeks
Patients with plasma cell myeloma treated with induction therapy or re-induction therapy, who at the time of study enrollment have documented evidence of stable disease response or better according to International Myeloma Workshop Consensus Panel
Chemotherapy refractory acute leukemia (AL) will be defined by not in achieving a hematological remission after two consecutive standard courses of induction therapy
AML relapsed or refractory to at least one attempt at induction or subjects not candidates for aggressive induction regimens
Patients younger than 50 years old, after first induction of chemotherapy, who are able to safely tolerate re-induction therapy with high dose chemotherapy are not eligible for this study (patients who are 50 years old or older or patients younger than 50 who are not able to tolerate an aggressive reinduction chemotherapy, based on the physician assessment, are still be eligible for this study if they fail their first induction)
Patients with AML must have had at least 2 prior therapeutic attempts including frontline induction.
Patients with ALL must have had at least 3 prior therapeutic attempts including frontline induction.
Subjects who are refractory* or who have relapsed** following first line AML therapy with cytarabine/anthracycline based chemotherapy, with or without a tyrosine kinase inhibitor. *Refractory to induction therapy is defined as never achieving CR, CRi or CRp (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI. or **First relapse is defined as untreated hematologic relapse (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI that induced a CR/CRi/CRp. Subjects are allowed to receive induction, consolidation, transplant and/or maintenance prior to achieving their first CR/CRi/CRp.
Patients with relapsed or refractory AML; patients must have failed at least one prior induction regimen for AML; the maximum number of prior lines of induction is 3
Patients must have at least received an appropriate induction therapy regimen. Patients with persistent leukemia after induction therapy, or with recurrence of leukemia at any time during the course of treatment (including allogeneic HSCT) are eligible;
Refractory to at least 1 cycle of induction chemotherapy
Platelets >= 100,000/mm^3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
Either achieved complete remission (greater than 12 weeks in duration) with initial induction/consolidation and have experienced relapse of disease or declined treatment with high-dose induction/consolidation
Eligible for induction by daunorubicin + cytarabine.
Pre-operative treatment with induction chemotherapy for breast cancer
Patients with WHO-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:
STEP 1 - INDUCTION/RE-INDUCTION
The patient received any induction chemotherapy regimen and may have received post-remission consolidation therapy prior to screening.
The patient has adverse risk disease or AML for which there is otherwise a substantial risk of relapse, which includes but is not limited to: adverse karyotype, FLT3 internal tandem duplication (ITD) mutation, history of antecedent hematologic disorder (AHD), therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, and/or presence of persistent MRD (detected by cytogenetics, molecular markers, or flow cytometry) at any point after the initial induction cycle.
Patient must be either primary refractory to one frontline induction therapy or relapsed after one frontline induction therapy; patients who do not achieve complete remission after induction therapy are also eligible
Radiation use as part of induction regimen or consolidation (within 90 days after completion of induction chemotherapy) is allowed
Refractory disease is defined by the failure to obtain a complete remission (CR) with a HDAC-containing or a standard induction regimen. Patients who require two cycles of induction therapy to attain a first CR are not considered to have refractory disease.
It must be at least 6 months since the last treatment with a \VPLD\ induction/re-induction type regimen (i.e. anthracycline, steroid, asparaginase and vincristine)
Refractory patients:\r\n* Patients must have received at least two attempts at remission induction, which may consist of up to two different therapy courses; Children's Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is one remission attempt
Within three days of starting the induction phase of therapy for ALL (B-cell, T-cell, or mixed phenotype)
Patients who are not eligible for standard anesthetic induction, e.g., those needing rapid sequence induction or awake fiberoptic bronchial intubation
Acute or chronic thrombocytopenia in patients with acute leukemia (myeloblastic or lymphoblastic) receiving induction or re-induction chemotherapy that is expected to induce marrow aplasia for at least 2 weeks; or
Patients undergoing AML induction chemotherapy with an anthracycline + cytarabine-based chemotherapy regimen
Anesthetic plan must include arterial line (femoral, radial, brachial, dorsalis pedis) either prior to induction of anesthesia or immediately after induction of anesthesia
Patient cannot previously have been on the trial for another induction, salvage, or consolidation attempt
Patients must have achieved a complete response to induction chemotherapy (+/- thoracic radiation therapy) assessed according to local habits (at least on a chest x-ray) at the time of study entry
Prior induction chemotherapy
Considered inappropriate for intensive remission induction therapy by an investigator
Receipt of induction chemotherapy
Planned use of cisplatin as induction chemotherapy.
Myelodysplastic syndromes requiring induction (myelosuppressive) chemotherapy
Subjects who are undergoing re-induction chemotherapy and have participated in this study during their first induction chemotherapy
Prior therapy with hydroxyurea, interferon, anagrelide, ruxolitinib, hypomethylating agents, Revlimid, thalidomide, steroids, other JAK inhibitors is allowed for AML patients who are back in chronic phase MPN, prior induction chemotherapy is allowed
Planned 3-4 drug systemic induction chemotherapy with a corticosteroid, vincristine and a single dose or multiple doses of asparaginase, with or without daunorubicin
MDS – may have achieved CR through either hypomethylating agent therapy, induction chemotherapy, or other therapy
Stable or better disease on re-staging scans following induction mFOLFIRINOX
Induction chemotherapy regimen
Patients must have previously untreated AML and be candidates for intensive induction chemotherapy; patients are allowed to have had prior hydroxyurea
Has AML or ALL and failed any prior induction therapy regimen or have relapsed after prior therapy
Patients that receive chemotherapy (induction or sequential)
Receiving induction treatment while hospitalized
Patient is currently undergoing AML-like intensive induction, re-induction/salvage, or consolidation chemotherapy, or planned to start such therapy within 1 week
Has completed or scheduled to begin 4-6 cycles of platinum-based induction chemotherapy that does not include a taxane\r\n* Induction may contain, but is not required to contain bevacizumab or cetuximab; induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina (UNC) principal investigator (PI) that there is no additional risk to the subject\r\n* Day 1 (D1) of treatment on LCCC1516 must be 21-42 days from the last day of induction, consistent with timing of standard of care maintenance
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study; orange juice is allowed
Patients must be willing and able to avoid consuming food and beverages containing grapefruit, star fruit or Seville oranges while on ibrutinib study therapy
Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax
Participants receiving any medications or substances that are moderate and strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), including enzyme-inducing anti-epileptic drugs (EIAEDs) within 14 days before the first dose of ponatinib will be excluded; this category includes phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, and oxcarbazepine\r\n* NOTE: participants must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period
In addition, grapefruit, grapefruit juice, seville oranges and star fruit should be avoided, as they inhibits CYP3A4
Participant consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.
Consumption of grapefruits, grapefruit products, Seville oranges (including marmalade that contains Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax.
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study.
For subjects in expansion cohort only: Ingestion of any food or drink containing grapefruit or Seville oranges, or St. John´s wort, within 7 days prior to receiving the first dose of AMG 330
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study
Received the following agents within 7 days prior to the first dose of venetoclax:\r\n* Steroid therapy for anti-neoplastic intent \r\n* Strong and moderate CYP3A inhibitors \r\n* Strong and moderate CYP3A inducers\r\n* Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
Subject has consumed grapefruit, grapefruit products, seville oranges (including marmalade containing seville oranges) or star fruit within 3 days prior to the initiation of study treatment
Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
Patients must avoid consumption of grapefruit, pomegranates, starfruit, Seville oranges or products containing the juice of each during the entire study and preferably 7 days before the first dose of study medications; orange juice is allowed
Patients requiring the following agents within 7 days prior to the first dose of venetoclax are excluded:\r\n* Steroid therapy for anti-neoplastic intent\r\n* Strong CYP3A inhibitors\r\n* Strong CYP3A inducers\r\n* Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax\r\n* NOTE: moderate CYP3A inhibitors and inducers should be used with caution and an alternative medication used, whenever possible
Consuming grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism
Consumption of grapefruit, grapefruit hybrids, pummelos, star-fruit, Seville oranges or products containing the juice of each within 7 days prior to study registration.
Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.
Consumption of grapefruit and related fruits within 7 days prior to initiation of study drug
Use of strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4, including certain herbal medications (eg, St. John's Wort) and consumption of grapefruit or grapefruit juice within 14 days or 5 x the half?life (whichever is longer) prior to the first dose of study drug.
Received the following agents within 7 days prior to the first dose of venetoclax:\r\n* Strong and moderate CYP3A inhibitors\r\n* Strong and moderate CYP3A inducers\r\n* Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
Patients must avoid grapefruit, grapefruit juice, supplements containing grapefruit juice, star fruit, and Seville oranges during the entire study, starting 7 days prior to the first dose of study drug
Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study
Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting study drugs
Consumption of grapefruit, grapefruit juice, pomegranates, star fruits, Seville oranges or products within 7 days prior to first dose
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study; NOTE: orange juice is allowed
Consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomelos, pomegranates, star fruits, Seville oranges or related products within 7 days prior to first dose
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 14 days prior to the dose of study medication, throughout the study, and until 2 weeks after the last dose of AZD1775 due to potential cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) interaction with the study medication; orange juice is allowed
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are not permitted during the study.
Patients currently taking warfarin, tamoxifen, phenytoin, diclofenac, tolbutamide, or ibuprofen are excluded secondary to potential inhibition of cytochrome P450 2C9 (CYP2C9); in addition patients that consume grapefruit juice and Seville orange juice must not consume these during the study
Participants taking a drug known to be strong inhibitors or inducers of isoenzyme CYP3A; participant must be off CYP3A inhibitors and inducers for at least 7 days prior to planned start of study treatment; NOTE: participants must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to planned start of study treatment and during the entire study treatment period due to potential CYP3A4 interaction
Is willing to abstain from grapefruit and Seville oranges (or juice) from 7 days before the first dose until study completion
Participants taking a drug known to be a strong inhibitor or inducer of isoenzyme CYP3A; participant must be off CYP3A inhibitors and inducers for at least 14 days prior to starting study drug; NOTE: participants must avoid consumption of Seville oranges (and juice), grapefruits or grapefruit juice, grapefruit hybrids, pomelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period
Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study
Patients must not be taking ketoconazole, dexamethasone, the dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice within two weeks of randomization and during the course of therapy; topical and inhaled steroids are permitted
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment throughout their time on study
Participants unwilling to exclude grapefruit juice and grapefruit from their diet.
Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pomelos, star-fruit, and Seville oranges
Grapefruit, Seville oranges or products containing either juice
Grapefruit, grapefruit juice, and other foods known to inhibit cytochrome P450 and PgP activity may increase everolimus exposures and should be avoided during treatment.
Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug.
Received the following agents within 7 days prior to the first dose of venetoclax: steroid therapy for anti-neoplastic intent; strong and moderate cytochrome P450 (CYP) 3A4 inhibitors or inducers; grapefruit/grapefruit products, seville oranges or star fruit within 3 days prior to the first dose of venetoclax
Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study treatment
Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
Patients must not eat grapefruit or drink grapefruit juice or plan to eat or drink them during study therapy
Consumed grapefruit or grapefruit products, seville oranges (including marmalade containing seville oranges), or star fruit within 3 days prior to the first dose of study treatment
Patients should avoid CYP3A4 inhibiting foods including grapefruit and Seville orange juice
Patients using Seville orange, star fruit, grapefruit and their juices, and St. John's Wort
Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pomelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study due to potential cytochrome P450 3A4 (CYP3A4) interaction with the study medication; orange juice is allowed
Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug.
Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor).
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients must agree to avoid grapefruit or grapefruit juice and Seville (sour) oranges during the entire study
NON-PROGRESSED DIPG (STRATUM 2): Patients must agree to avoid grapefruit or grapefruit juice and Seville (sour) oranges during the entire study
Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star fruit within 3 days prior to first dose of venetoclax
Intake of grapefruit, grapefruit juice, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days prior to day 1
Intake of grapefruit, grapefruit juice, Seville oranges, or other products containing grapefruit or Seville oranges within 14 days prior to day 1 and during the study
Consumption of food or beverages containing grapefruit juice within 7 days of study drug dosing
Subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism
Willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
Patients who are currently receiving or consuming\r\n* Medications that are known strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) =< 14 days of starting study treatment\r\n• Medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes =< 7 days prior to start of study treatment\r\n* Amiodarone =< 180 days prior to start of study treatment\r\n* Grapefruit, grapefruit juice, pomegranates, star fruits, Seville oranges or products =< 7 days prior to start of study treatment\r\n* Warfarin (or derivatives)
Must abstain from grapefruit juice
Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are not permitted during the study.
Seville oranges within 5 days before the first dose of study drugs and during the study.
Willingness to refrain from grapefruit juice for 7 days prior to and for 7 days during the study
Consumption of grapefruit or grapefruit juice is not permitted during the study; patients should not consume food or beverages containing the fruit or juice of grapefruits or Seville oranges within 7 days before the first dose of study drug and throughout the study
Consumed grapefruit juice or grapefruit containing products within 7 days of the first planned ranolazine dose
Participants who have taken any medicines that are inducers, inhibitors or substrates of select cytochrome (CYP) isozymes within the past 3 months will be excluded; participants who have consumed either grapefruit juice or Seville orange juice in the past 7 days will be excluded
Willingness to abstain from grapefruit juice, alcohol, and concomitant medications during study
Food or beverages containing grapefruit, Seville oranges, or Star fruit within 5 days before the first dose of study drugs. Note that food and beverages containing grapefruit, Seville orange, or Star fruit are not permitted during the study.
Food or beverages containing grapefruit within 5 days before the first dose of study drug. Note that food and beverages containing grapefruit are not permitted during the study.
Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are prohibited during the study.
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
As there is potential for hepatic toxicity with nivolumab or nivolumab non-drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution.
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
Drugs with a predisposition to hepatoxicity should be used with caution
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Drugs with predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
Drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatoxicity should be used with caution in subjects treated with nivolumab-containing regimen.
As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
Requires therapy with agents that have a predisposition for hepatoxicity
Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks
Irinotecan, temozolomide and mammalian target of rapamycin (mTOR) inhibitor exposure:\r\n* Patients who have received prior single agent therapy with irinotecan, temozolomide, or an mTOR inhibitor, excluding ABI-009, are eligible\r\n* Patients who have received prior therapy with ABI-009 are not eligible\r\n* Patients who have previously received irinotecan and temozolomide in combination without progressive disease while on therapy are eligible\r\n* Patients who have previously received irinotecan and temozolomide in combination and had significant toxicity with these two drugs are not eligible\r\n* Patients who have received prior therapy with all three agents in combination (i.e. irinotecan, temozolomide, and an mTOR inhibitor) are not eligible
Known hypersensitivity to irinotecan
Patients previously treated with irinotecan are eligible for this study
Prior therapy with irinotecan (for expansion phase II only)
Documented progression on and/or intolerance/hypersensitivity to both paclitaxel and irinotecan (Part B only)
irinotecan,
Any history of hypersensitivity to irinotecan
Prior treatment with PM01183, trabectedin (Yondelis®) or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
Allergy or sensitivity to irinotecan or cranberry-grape juice, or any of the irinotecan tablet excipients. .
No history of severe reactions to fluorouracil (5-FU), irinotecan hydrochloride (irinotecan), or a monoclonal antibody
Patients who have required toxicity related dose reductions of greater than 50% of the original dose of infusional 5-FU and/or irinotecan during the administration of FOLFIRI/bevacizumab
Phase 2: Received prior therapies with eribulin mesilate or irinotecan.
Prior treatment with irinotecan or temozolomide is permitted
Patients with a history of an anaphylactic reaction to irinotecan.
Prior treatment with a Wee1 inhibitor or any irinotecan containing regimen
History of hypersensitivity to AZD1775, irinotecan, or any excipients of these agents
Patients must be irinotecan refractory; patients must have progressed on prior irinotecan therapy but must be able to tolerate standard irinotecan doses
No prior treatment with oxaliplatin, irinotecan (irinotecan hydrochloride), fluorouracil or capecitabine
History of hypersensitivity reactions to products containing irinotecan (irinotecan), topotecan or other topoisomerase inhibitors, gadolinium contrast agents or lipid products
Prior treatment with irinotecan and/or bevacizumab
Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer.
Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer
Participant had prior exposure to topotecan, irinotecan or any other topoisomerase I inhibitors.
Patients who have severe hypersensitivity to irinotecan hydrochloride (HCl)
Patients must not have received prior irinotecan-based chemotherapy (e.g. irinotecan hydrochloride, leucovorin calcium, fluorouracil, and oxaliplatin [FOLFIRINOX] or FOLFIRI)
Patients must not have known hypersensitivity to irinotecan, fluorouracil, or leucovorin
Patients must not have had any prior treatment with oxaliplatin or irinotecan hydrochloride (irinotecan) within 3 years prior to registration; patients must not have had prior chemotherapy in metastatic setting; prior abdominal radiation therapy is not allowed
History of allergic reactions attributed to the following: \r\n* Camptothecin derivatives (e.g., topotecan [topotecan hydrochloride], irinotecan, or exatecan [exatecan mesylate]) \r\n* Any ingredients contained within the liquid irinotecan solution (e.g., sorbitol) or\r\n* Any antiemetics or antidiarrheals appropriate for administration with study therapy (e.g., loperamide or dexamethasone)
Known hypersensitivity to irinotecan
Prior irinotecan treatment
Taking any other systemic anticancer agent (docetaxel, doxorubicin, irinotecan)
Patients previously treated with irinotecan-containing regimen
Hypersensitivity to 5FU (fluorouracil), oxaliplatin (or other platinum agents), irinotecan (irinotecan hydrochloride) (or to their excipients)
Prior treatment with irinotecan, topotecan, or dinutuximab.
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
Prior intolerance to irinotecan and/or bevacizumab despite dose reduction
Subject must have received at least oxaliplatin-, and irinotecan-based regimens with bevacizumab and with, cetuximab or panitumumab if KRAS wildtype and are refractory to irinotecan;
Pancreatic adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator.
For patients to be treated with a regimen containing irinotecan:
Known hypersensitivity to irinotecan
Prior treatment with a topoisomerase I inhibitor (i.e. irinotecan, topotecan)
Has a previous treatment with irinotecan
Any prior therapy with irinotecan
Prior treatment with a topoisomerase-I inhibitor (e.g., topotecan, irinotecan)
Prior intolerance of irinotecan or necessity for dose reduction greater than 20%
Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
Participants may not have received any prior camptothecin, including but not limited to: topotecan, irinotecan
Prior irinotecan treatment.
History of intolerance to irinotecan at dose-intensity of 125 mg/m^2/2 weeks or lower
Progression on irinotecan containing regimen
Patients may not previously have received irinotecan, topotecan or other topoisomerase I inhibitor
Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens
- irinotecan
14 days from administration of vincristine or irinotecan
DISEASE CHARACTERISTICS:\n\n          -  Histologically confirmed diagnosis of iNHL (Follicular lymphoma grade 1, 2, 3a;\n             marginal zone lymphoma; small lymphocytic lymphoma or lymphoplasmacytic lymphoma)\n             after treatment with at least 1 or more prior rituximab-containing regimens.\n\n               -  Anti-CD20 mAb-refractory disease is defined as progressive disease while on\n                  rituximab (or another treatment of an anti-CD20 monoclonal antibody) or\n                  progression within 6 months of rituximab-containing (or another treatment of an\n                  anti-CD20 antibody-containing) therapy.\n\n               -  Anti-CD20 mAb-sensitive disease is defined by a response to a prior\n                  rituximab-containing (or another treatment of an anti-CD20 monoclonal antibody)\n                  regimen, and relapse more than 6 months from the last administration of\n                  rituximab-containing (or another treatment of an anti-CD20 antibody-containing)\n                  therapy.\n\n          -  Measurable disease:\n\n               -  At least one lymph node group ? 1.5 cm in longest transverse dimension. Patients\n                  with cutaneous only disease may be enrolled if they have a clearly measurable\n                  skin lesion.\n\n               -  Relapsed or Refractory iNHL that has progressed during or following 1 or more\n                  prior systemic rituximab-containing (or another treatment of an anti-CD20\n                  antibody-containing) regimens for lymphoma\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No anti-lymphoma 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        Performance Status\n\n        • ECOG 0, 1, or 2\n\n        Renal Function • Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ? 1.5 X\n        ULN\n\n        Bone Marrow Reserve\n\n          -  Platelets ?30,000/uL\n\n          -  Hemoglobin ? 8g/dL\n\n          -  Absolute Lymphocytes ?800/uL\n\n          -  ANC/AGC ?750/uL\n\n        Hepatic Function\n\n          -  Total bilirubin ? 2.0 X ULN (unless Gilbert's Syndrome or disease infiltration of\n             liver is present)\n\n          -  AST, ALT ? 3.0 X ULN, or ? 5.0 X ULN (if liver lymphoma is present)\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 or severe cardiac dysfunction\n\n          -  No history of uncontrollable 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 active CNS involvement with lymphoma\n\n          -  No psychiatric illness/social situation that would limit compliance\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 disease requiring systemic immunosuppressive therapy (inhaled or topical steroids\n             are allowed). Adrenal replacement steroid doses ? 10 mg daily prednisone equivalent\n             are permitted in the absence of active autoimmune disease.\n\n          -  No known histologic transformation from iNHL to DLBCL
Treatment failure of rituximab monotherapy (Cohort A) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (Cohort B) for treatment of PTLD. Note: Subjects with CD20 negative disease are eligible to enroll without prior anti-CD20 therapy after failure of first-line treatment (reduction of immunosuppression is not considered first-line therapy) and discussion with the sponsor's medical monitor.
Patients who have received prior treatment for lymphoma are not eligible\r\n* NOTE: Patients may have received corticosteroids for lymphoma for 10 or fewer days at any dose (no washout period required)\r\n* NOTE: Patients may have received up to 1 prior dose of rituximab before registration; in this case, patients will only receive 3 doses of rituximab on study
Patients who have received chemotherapy (including monoclonal antibodies) or radiotherapy, administered for any condition, within 4 weeks prior to registration are not eligible\r\n* NOTE: Patients may have received one dose of rituximab prior to enrollment; in such cases, patients will only continue with 3 doses of rituximab during induction (4 total doses)
TREATMENT: Patients should have been off conventional therapy for at least 1 week prior to entry in this study, including rituximab
Avoid conceiving for at least 12 months after the last dose of rituximab, or according to the local rituximab Prescribing Information or Summary of Product characteristics (SmPC); at least 28 days after the last dose of any other study drug.
mAb (including rituximab) within 2 weeks of enrollment
Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent; patients with a prior reaction to rituximab are permitted if the investigator feels that this reaction is manageable with standard supportive care measures and would otherwise be comfortable administering rituximab outside of the clinical trial setting
Part 2: Subjects who have received any amount of rituximab within 365 days of planned dose day 1 must have a serum rituximab level of <500 ng/mg documented by the study's reference laboratory prior to the initiation of dosing. Potential subjects who have received any other anti CD20 MAb therapy (obinutuzumab, ofatumumab, or ibritumomab tiuxetan) must be at least 8 half-lives past their last dose prior to initiation of study drug dosing. Washout periods for these drugs are as follows:
Has insurance coverage or is willing to pay for protocol therapy (rituximab x 4 or Zevalin x 1)
No prior rituximab unless HCLv patient
Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (example, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment
No prior cytotoxic chemotherapy; prior therapy with single-agent rituximab is permitted; prior involved-field radiotherapy to symptomatic nodal sites of involvement is also permitted
Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease
Treatment with rituximab or other anti-B cell specific antibodies within previous 3 months
Use of rituximab and other anti-cluster of differentiation 20 (CD20) antibodies known to have the same epitope as rituximab or anti-CD20 for which the epitope is unknown within 3 months prior to start of lymphodepletion
mAb (including rituximab) within 2 weeks of enrollment
Relapsed or refractory to any prior rituximab-containing regimen.
Received rituximab within 4 weeks of study start.
Rituximab within 12 months prior to study registration; only exception will be if rituximab was given for indications other than the treatment of aggressive lymphoma, or for one prior cycle of treatment
Previous treatment with any chemotherapy and/or rituximab or other monoclonal antibody.
A known hypersensitivity to rituximab, HH1, Betalutin or murine proteins or any excipient used in rituximab, HH1 or Betalutin.
Rituximab resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last course of treatment with a rituximab containing regimen including rituximab maintenance)
Any prior treatment with rituximab or any other anti-CD20 agent must have been > 6 months prior to the first dose of PRTX-100
Planned to receive chemotherapy for 6 cycles which the treating physician plans to utilize for pegfilgrastim to minimize risk for neutropenic fever, including but not limited to rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP), rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (R-EPOCH), and rituximab, cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, administered on a hyperfractionated schedule (R-HyperCVAD), cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP), and dexamethasone, methotrexate, ifosfamide, asparaginase, and etoposide (SMILE)
Patients must have relapsed (recurrence after complete response or presented progression after partial response) after last rituximab-containing therapy (other previous treatment lines after rituximab are allowed). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy is allowed for patients who responded to single-agent rituximab); at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to PI3K is acceptable (except to copanlisib) provided there is no resistance. Patients with prior intolerance to PI3K inhibitors other than copanlisib are eligible.
Progression free interval or treatment free interval of less than 12 months since the last rituximab containing treatment (including rituximab maintenance). For patients considered unwilling/unfit to receive chemotherapy : progression free interval or treatment free interval of less than 6 months since the last rituximab containing treatment (including rituximab maintenance), as assessed by the investigator
Able to start the protocol therapy (1st dose of rituximab) between day 28-60 post-transplant
Patients must have received at least 1 prior rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, etc.)
No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent rituximab is permitted
Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease
Patients will be eligible if the treatment phase consisting in a Rituximab combined with any anthracycline-containing chemotherapy regimen without consolidation with autologous stem cell support (e.g., 6 cycles of CHOP14-21, DA-EPOCH, Mega-CHOP or 12 weeks of VACOP-B or MACOP-B).
At least 6 courses of Rituximab should be administered
History of rituximab or intravenous bevacizumab therapy within six weeks
Received rituximab within 4 months of blood collection for lymphoblastoid cell line (LCL) initiation (unless circulating CD19+ B are >= 2%)
Patients with history of non-response to both pentostatin plus rituximab and to bendamustine plus rituximab
Previous rituximab
Arms A/B – eligible for treatment with ifosfamide, carboplatin, and etoposide (+/- rituximab)
Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (eg, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment
Has receive rituximab
Patients with known hypersensitivity to lenalidomide and/or rituximab
A treatment regimen containing a therapeutic anti-CD20 antibody (e.g., rituximab, ofatumumab, obinutuzumab) AND
Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab
Participants who have received more than one (1) prior cycle of chemotherapy similar to cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) or EPOCH with or without rituximab
Rituximab therapy within the 12 months prior to study entry; participants treated with rituximab within 12 months prior to study registration are eligible only if it was given for indications other than the treatment of aggressive lymphoma
Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab
Previously exposed to rituximab as part of prior lines of treatment.
Did not achieve at least a partial response (PR) to a standard salvage regimen (e.g., R-ICE; rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP; rituximab, dexamethasone, cytarabine, cisplatin)
Prior exposure to either bortezomib or rituximab is not an exclusion criteria
Patients with known hypersensitivity to lenalidomide and/or rituximab (CD20+ patients only)
Contraindication to receive any of the individual components of CHOP, rituximab or obinutuzumab
Previously treated with at least one prior systemic chemotherapy, immunotherapy or chemoimmunotherapy and have received at least 2 previous doses of rituximab.
Investigator considers rituximab monotherapy appropriate.
Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab
Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions)
Immunosuppressants (e.g. Cyclosporin, Rapamycin, Tacrolimus, Rituximab, Alemtuzumab, Natalizumab, etc.).
Histological confirmation of relapsed/refractory diffuse large B-cell lymphoma after prior rituximab and anthracycline-containing systemic treatment regimen such as rituximab-cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine (oncovin), and prednisone (R-CHOP), rituximab-etoposide, vincristine, and doxorubicin (R-EPOCH), rituximab-hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (R-HyperCVAD), etc; a biopsy immediately before enrollment is not required
Subjects must have received no more than 2 prior systemic therapies for lymphoma; prior therapy with systemic rituximab monotherapy or conventional chemotherapy (i.e. bendamustine, cyclophosphamide, vincristine, and prednisone [CVP] or other) +/- rituximab for indolent non-Hodgkin lymphoma (NHL) +/- maintenance/extended-use rituximab will count as 1 line of systemic therapy
Previously completed anthracycline-based induction chemotherapy with standard regimens including rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP), dose adjusted (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide (EPOCH), and rituximab (R), and R-hyper cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine (CVAD); patients need a minimum of 6 cycles of treatment; initial treatment with pidilizumab must be administered between 30-90 days from last dose of induction chemotherapy
For cohort 1: Male or female subjects with histologic proof of follicular lymphoma grade 1, 2, or 3a relapsing after at least one prior systemic therapy that included rituximab (or other monoclonal CD20 antibody); patients should have rituximab-sensitive disease defined as a documented complete or partial response lasting at least 6 months after the last rituximab containing therapy or rituximab-refractory disease defined as stable or progressive disease within 6 months of the last rituximab-containing therapy
For cohort 2: Male or female subjects with histologic proof of follicular lymphoma grade 1, 2, or 3a relapsing after at least two prior systemic therapies, one of which must include rituximab (or other monoclonal CD20 antibody) or histologic proof of DLBCL relapsing after at least two prior systemic therapies, one of which must include rituximab (or other monoclonal CD20 antibody) and are considered ineligible for high dose therapy/autologous stem cell transplant
Patients must be refractory to the last rituximab-based treatment, defined as no response or response lasting < 6 months after completion of treatment. Time interval to assess refractoriness will be calculated between the end date (last day) of the last rituximab-containing regimen and the day of diagnosis confirmation of the subsequent relapse.
Extra-corporeal photopheresis (ECP) or rituximab therapy within 4 weeks prior to enrollment
Cohort B-3: 1) Histologically-confirmed DLBCL 2) Prior standard rituximab + anthracyclin containing regimen, received or not eligible or considered candidate of HD-ASCT 3) Measurable disease (IWG -Lugano 2014)
Participants with new immunosuppressive medication, extra-corporeal photopheresis or rituximab therapy initiated in the 4 weeks prior
Disease that is refractory to the last prior rituximab-containing therapy defined as either
Relapse after the last rituximab-containing therapy <12 months since last dose of rituximab, OR
Rituximab treatment within the last 12 months before the first dose of study drug.
Relapse after the last rituximab-containing therapy <12 months since last dose of rituximab, OR
Failure to achieve at least a MR after the last rituximab-containing therapy.
Subjects must have rituximab-refractory disease, defined as lack of CR or PR or PD within 6 months of last dose.
Agrees to protocol-defined use of effective contraception (for women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose of study drug, whichever is later; for men, these restrictions apply for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later)
Having received rituximab within the prior 2 months
Patients' NHL must have progressed after at least 1 prior rituximab containing regimen.
off rituximab for at least 14 days before the screening visit and be confirmed to have either no response or have disease progression after rituximab treatment.
Prior exposure to rituximab
Subject with diffuse large B-cell lymphoma must have relapsed diffuse large B-cell lymphoma or must have progressed after salvage therapy (with or without standard chemotherapy) for diffuse large B-cell lymphoma. The subject must have received first line therapy with Rituximab-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP) [or a similar standard rituximab-containing front-line chemoimmunotherapy regimen including, but not limited to Etoposide, Prednisone, Vincristine (Oncovin), Cyclophosphamide, Doxorubicin (Hydrochloride) + Rituximab (EPOCH + R); Rituximab, Cyclophosphamide, Etoposide, Procarbazine, Prednisone (RCEPP); Rituximab, Cyclophosphamide, Mitoxantrone (Novantrone), Vincristine (Oncovin), Prednisone (RCNOP); Dose-adjusted-Etoposide, Prednisone, Vincristine(Oncovin), Cyclophosphamide, Doxorubicin (Hydrocloride) (DA-EPOCH); and Rituximab, Cyclophosphamide, Etoposide, Vincristine (Oncovin), Prednisone (RCEOP)].
Subject progressed during or within 3 months of completion of a planned course of first-line therapy with Rituximab-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP) or an equivalent regimen;
Refractory to or relapse following a rituximab/anthracycline first-line regimen
Intravenous rituximab within 30 days of starting treatment
Prior exposure to rituximab.
Received rituximab containing a multi-agent therapy for the treatment of NHL.
Completion of a full course of first line immunochemotherapy including rituximab OR completion of 4 cycles of first line immunochemotherapy including rituximab if intolerant of treatment (e.g. which include, but are not limited to, rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine sulfate (Oncovin) and prednisone [R-CHOP], rituximab, cyclophosphamide, vincristine sulfate, and prednisone [R-CVP], bendamustine- R)
Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen
Refractory to any previous regimen containing rituximab (defined by participants who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen)
Arm B: Relapsed from or refractory to ? 2 prior chemotherapy regimens with ? 1 regimen containing rituximab
Arm C: Relapsed from or refractory to ? 2 prior chemotherapy regimens with ? 1 regimen containing rituximab or failed 1 prior rituximab-containing regimen and unable to tolerate additional multiagent chemotherapy
All patients with untreated Rai stage III-IV are eligible for this protocol; prior treatment with single-agent rituximab permitted; OR patients with untreated Rai stage 0-II who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL); prior treatment with single-agent rituximab permitted
Received previous treatment with rituximab that was not effective.
Previously untreated or who received a maximum of one cycle of combination chemotherapy (i.e. rituximab-cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone [R-CHOP], R-EPOCH, or rituximab, hyperfractionated cyclophosphamide, vincristine sulfate adriamycin dexamethasone [R-hyperCVAD]) within 4 weeks of study entry except patients who require dose reduction after the first cycle of off-study R-EPOCH
Known hypersensitivity to rituximab
First or subsequent relapse following at least one induction therapy regimen containing rituximab in combination with an anthracycline or rituximab in combination with an alkylating agent
Refractory to rituximab: defined as disease progression while receiving or within 6 months of completing either weekly rituximab induction therapy, or rituximab-based chemoimmunotherapy induction
Previous treatment with rituximab or other monoclonal antibodies, or temozolomide.
For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 mAb and for which no curative option exists as determined by the investigator
Subjects with histologically confirmed relapsed or refractory DLBCL who have received at least 1 prior rituximab containing chemotherapy regimen but no more than 5 prior lines of therapy
Intolerable toxicity to prior rituximab therapy.
Not a candidate for treatment with rituximab as a single-agent
Any prior treatment with rituximab
Patients must have received prior Rituximab-containing therapy.
Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL
Lymphoma that is refractory to rituximab and to an alkylating agent
Patient must have been previously treated for B cell non-Hodgkin lymphoma with any of the allowable below:\r\n* First-line treatment with rituximab and an anthracycline-based chemotherapy\r\n* Monotherapy rituximab, dosed prior to first-line rituximab combined with anthracycline containing chemotherapy, or as maintenance therapy\r\n* Radiotherapy as part of the first-line treatment plan including anthracycline and rituximab
If rituximab previously given, lymphoma must have relapsed >= 12 months after last rituximab dose
Patients must have received prior rituximab-containing therapy.
Circulating levels of rituximab > 75.0 µg/ml
Rituximab within six weeks
Contraindication to bendamustine, rituximab, or obinutuzumab
Relapsed from or refractory to at least one treatment containing rituximab or another anti-CD20 based immunotherapy combined with anthracycline- or anthracenedione-based chemotherapy
Rituximab-sensitive disease, defined as a Partial Remission (PR) or Complete Remission (CR) to the last rituximab-containing therapy lasting at least 6 months following completion of therapy. Last rituximab-containing therapy is defined as the last therapy regimen containing at least one full dose of rituximab.
Rituximab-refractory disease, defined as failure to respond to or progression within 6 months of completing rituximab or rituximab-containing combination therapy.
Rituximab-sensitive iNHL, defined as a partial or complete response to their last prior treatment with rituximab or a rituximab-containing regimen lasting at least 6 months following completion of rituximab treatment.
Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 RRCML criteria, which requires therapy.
By standard clinical criteria, be medically appropriate to receive rituximab and anthracycline-containing induction therapy and high-dose chemotherapy with AHCT
In addition to the above, subjects meeting the following criteria will be enrolled in the pre-phase arm of the study, until the accrual target for that arm is reached:\r\n* Age >= 70 years OR KPS =< 70\r\n* Pathologically confirmed diagnosis of DLBCL, with or without simultaneous or antecedent indolent lymphoma\r\n* Previously untreated for DLBCL\r\n* Intended initial treatment to include >= 2 cycles of R-CHOP; rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride (R-EPOCH); or rituximab, cyclophosphamide, etoposide, procarbazine, and prednisone (R-CEPP) using standard doses and schedule; R-CHOP chemoimmunotherapy may be given every 14 days or every 21 days
Patients with Burkitt lymphoma or any patient receiving rituximab-cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate / ifosfamide, etoposide, high-dose cytarabine (R- CODOXM/IVAC)
Patient must have histologic or cytological diagnosis of de novo diffuse large B-cell lymphoma (DLBCL) (including lymphomas/leukemias newly transformed to DLBCL) and be scheduled to receive first line chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride (R-EPOCH); OR patient who will undergo consolidative external radiotherapy after completion of chemotherapy are eligible
Relapsed from or refractory to at least one treatment containing rituximab combined with anthracycline-based chemotherapy
Receiving any other investigational agent that would be considered as a treatment for the lymphoma; NOTE: rituximab maintenance and patients participating on Mayo Clinic vitamin D study are allowed
Had prior exposure to rituximab, natalizumab, vedolizumab, or alemtuzumab.