Patients must have had histologic verification of malignancy at original diagnosis or relapse\r\n* Parts A & C: patients with recurrent or refractory solid tumors, without central nervous system (CNS) tumors or known CNS metastases, are eligible; note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated\r\n* Part B1: patients with relapsed or refractory neuroblastoma\r\n* Part B2: patients with relapsed or refractory osteosarcoma\r\n* Part B3: patients with relapsed or refractory rhabdomyosarcoma\r\n* Part B4: patients with relapsed or refractory Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET)\r\n* Part B5: patients with relapsed or refractory Hodgkin lymphoma\r\n* Part B6: patients with relapsed or refractory non-Hodgkin lymphoma\r\n* Part B7: patients with unresectable melanoma or metastatic melanoma or relapsed melanoma or refractory melanoma\r\n* Part B8: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without Response Evaluation Criteria in Solid Tumors [RECIST] measurable lesion)\r\n* Once the dose-escalation portion of Part A is completed, cohorts that are open concurrently for eligible patients (including Parts B and C and potential pharmacokinetic [PK] expansion cohorts) may be selected at the treating physician’s discretion pending slot availability; in the event a disease group cohort in Part B is completed after the initial stage of Simon’s optimal two-stage design, for selected disease cohorts, a corresponding cohort in the same disease group for select disease types will be open in Part D:\r\n* Part D1: Patients with relapsed or refractory neuroblastoma\r\n* Part D2: Patients with relapsed or refractory osteosarcoma\r\n* Part D3: Patients with relapsed or refractory rhabdomyosarcoma\r\n* Part D4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET \r\n* Part D5: Patients with relapsed or refractory non-Hodgkin lymphoma\r\n* Part D6: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without RECIST measurable lesion)\r\n* Part E3: Patients with relapsed or refractory rhabdomyosarcoma\r\n* Part E4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET
Refractory cytopenia with unilineage dysplasia (RCUD) (includes refractory anemia (RA))
Part B: Patients with relapsed or refractory neuroblastoma
Part C: Patients with relapsed or refractory medulloblastoma or CNS PNET
Part D: Patients with relapsed or refractory rhabdomyosarcoma
Relapsed or relapsed/refractory multiple myeloma (MM) with progressive disease (PD) parameters according to International Myeloma Working Group (IMWG) criteria\r\n* Refractory is defined as experiencing less than minimal response to or PD within 60 days of the most recent line therapy\r\n* Relapsed is defined as patients requiring salvage therapy for PD who are not refractory to the most recent line of therapy
Diagnosis of multiple myeloma (MM) with relapsed and/or refractory disease. Participants must have received at least 3 prior lines of therapy. Participants must have previously received all of the following therapies and must be refractory to the last line of therapy prior to entering the study:
Subjects who have previously participated in Merck pivotal trial NCT02576977: Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (RRMM) (MK-3475-183/KEYNOTE-183).
Refractory to or relapsed after at least 1 prior treatment line.
Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of therapy, or a 50% increase of baseline disease measurements after achieving a clinical response
Confirmed diagnosis of a relapsed or refractory malignancy in 1 of 2 treatment groups:
Diagnosis of relapsed or refractory lymphoid malignancy for which there are no available therapies.
Pathologically confirmed relapsed or refractory lymphoma
Confirmed evidence of relapse/disease progression from immediately prior MM therapy or relapsed and refractory to the immediately prior treatment; relapsed and refractory disease is defined as those who are non-responsive (< minimal response) on salvage therapy or experience disease progression within 60 days of last therapy in patients who have achieved an MR or better to previous therapy; relapsed disease is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy but does not meet IMWG criteria for relapsed and refractory
Diagnosis of one of the following:\r\n* Relapsed/refractory peripheral T-cell lymphoma of any subtype including mycosis fungoides and Sezary syndrome of advanced stage (IIB-IVB)\r\n** For the expansion cohort: patients must have biopsy-proven T-cell lymphoma and measurable disease\r\n* Relapsed/refractory DLBCL (up to 6 DLBCL patients are allowed in the dose-escalation portion of the study)\r\n* Relapsed/refractory Hodgkin lymphoma (HL)\r\n* Note: extracorporeal photopheresis is NOT considered a systemic therapy for this study
Asparaginase refractory disease, defined by any one of the following:
Relapsed and relapsed/refractory multiple myeloma requiring systemic therapy
Relapsed or refractory to the most recently received therapy.
All pts must have received prior lenalidomide therapy and been determined to be refractory, relapsed, or intolerant.
For Daratumumab + lenalidomide + dexamethasone (D-Rd) regimen: relapsed or refractory disease
Relapsed or refractory disease after at least 1 prior regimen, defined using the 2014 Lugano classification
Patient must have disease that has either relapsed or is refractory to prior therap
Part D only: Patients diagnosed with CLL who are intolerant to, or have disease that is relapsed/refractory after, at least two prior therapies
Part F only: Patients with documented HTLV-1 infection and histologically or cytologically proven ATLL of any stage, and who are intolerant to, or have disease that is relapsed/refractory after, at least one prior therapy
ALK+ ALCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen including an anthracycline, if not contraindicated, and prior brentuximab; prior crizotinib or other ALK inhibitor therapy, while recommended, is not mandatory; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
MCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen and prior ibrutinib or other BTK inhibitor therapy; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
BCL6+ DLBCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included an anthracycline, if not contraindicated; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
INCLUSION - INFUSION: Any patient, regardless of age or sex, with measurable EBV-positive Hodgkin’s or non-Hodgkin’s lymphoma, (regardless of the histological subtype) or EBV (associated)-T/NK- or B cell lymphoproliferative disease\r\n* The first 3 patients enrolled will be adults; patients <18 years of age are eligible if those first 3 patients do not experience dose limiting toxicity considered to be primarily related to the EBVST or nivolumab\r\n* Patients with relapsed or refractory lymphoma who failed or are ineligible for an autologous hematopoietic cell transplantation are also eligible for this study; and\r\n* Hodgkin’s lymphoma patients in second relapse or first relapse and refractory to at least two lines of salvage chemotherapy including brentuximab vedotin or primary refractory disease after at least two lines therapy, or\r\n* Non- Hodgkin’s lymphoma patients in first relapse and/or refractory to at least one salvage chemotherapy or with primary refractory disease after at least two lines of therapy or in second or subsequent relapse, or\r\n* T/NK- or B lymphoproliferative disease in first relapse and/or refractory to at least one salvage chemotherapy or with primary refractory disease after at least two lines of therapy or in second or subsequent relapse
TREATMENT INCLUSION: Diagnosis and clinical course falling into one of the following categories:\r\n* Hodgkin lymphoma refractory to second line chemotherapy; relapsed or progressive after high dose therapy/autologous stem cell transplantation; relapsed or progressive after treatment with brentuximab or a checkpoint inhibitor\r\n* Aggressive non-Hodgkin lymphoma refractory to second line chemotherapy; relapsed or progressive after high dose therapy/autologous stem cell transplantation\r\n* ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma refractory to first line chemotherapy; relapsed after first line therapy (possibly including high dose therapy/autologous stem cell transplantation)\r\n* ALK-positive anaplastic T cell lymphoma refractory to second line therapy; relapsed after second line therapy
Refractory (no prior CR/CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. For subjects with refractory disease and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
Histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy:
For subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT
The patient has confirmed relapsed or refractory MM
Previous treatment with nelarabine for relapsed or refractory disease
requiring treatment for relapsed or relapsed/refractory disease
refractory to bortezomib
Men and women, 18 years or older, with advanced, relapsed or refractory solid tumors, Multiple Myeloma (MM) or non-Hodgkin's lymphoma (NHL) in Part A. In Part B, relapsed or refractory CD20-positive NHL subjects only.
AML relapsed or refractory to prior therapy, or ? 60 years of age and not a candidate for other therapies Phase 2a:
Patients must have relapsed or refractory disease following at least two prior platinumcontaining chemotherapy regimens
Patients with T-cell lymphoma (untreated, relapsed or refractory) (Phase II)
Patients with previously untreated or relapsed/refractory disease will be eligible
Participants must have a diagnosis of acute lymphoblastic leukemia and disease meets at least one of the following criteria:\r\n* Relapsed or refractory to chemotherapy as defined by ? 5% leukemic blasts in the bone marrow\r\n* Relapsed after hematopoietic stem cell transplantation (HSCT)
Relapsed, relapsed and refractory or refractory multiple myeloma patients who have received > 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD28 monoclonal antibody
History of refractory systemic infection.
Patients must have histologic evidence of relapsed or refractory B-cell ALL
Patient must have relapsed/refractory disease with an indication for treatment
Osteosarcoma cohort only: Subjects with osteosarcomas must have relapsed or become refractory to conventional therapy and have received a regimen including some combination of high-dose methotrexate, doxorubicin, cisplatin, and/or ifosfamide.
Patients must be either refractory to or relapsed after 1 line of therapy
Relapsed or relapsed/refractory disease
Subjects must have relapsed/refractory DLBCL or relapsed/refractory FL\r\n* For DLBCL, patients must have relapsed after, declined, or considered ineligible for high-dose chemotherapy and autologous stem cell transplantation\r\n* For FL, in addition to relapsed/refractory disease status, patients must have received therapy with CD20 antibody-directed therapy, and must have an indication for treatment; FL eligibility also requires patients have no standard options with curative potential, nor options with more favorable risk/benefit ratio in the judgment of the investigator
Relapsed or refractory B-precursor ALL defined as one of the following:
Relapsed or refractory disease after first or later salvage therapy
Must have biopsy-proven primary refractory disease or relapsed disease after front-line chemo-immunotherapy (with anti-CD20 monoclonal antibody [mAb]) in combination with anthracycline-based chemotherapy) or at least one of the following\r\n* For subjects with DLBCL: relapsed or refractory disease after ? 2 prior line(s) of therapy; for both de novo and transformed disease, patients must have received at least 1 prior regimen with anti-CD20 mAb and anthracycline\r\n* For subjects with FL or SLL: relapsed or refractory disease after ? 2 prior line(s) of therapy\r\n* For subjects with CLL: must be relapsed or refractory disease and\r\n** with no unfavorable cytogenetics and have failed ? 3 prior line(s) of therapy\r\n** with unfavorable cytogenetics including del17p/mutated p53 or unmutated immunoglobulin heavy chain variable region relapsed or refractory disease after ? 2 prior line(s) of therapy which must have included ibrutinib\r\n* For subjects with MCL: relapsed or refractory disease after at least 1 prior regimen with chemoimmunotherapy\r\n* For subjects with Burkitt’s: relapsed or refractory disease after at least 1 prior line of therapy\r\n* Any patient, with subtypes listed above, having either failed autologous HSCT after at least 1 prior regimen, or those patients ineligible for, but not an appropriate candidate, or not consenting to autologous HSCT
Relapsed or refractory after at least one prior treatment regimen
Patients must have relapsed (first or greater relapse) or refractory T-cell acute lymphoblastic leukemia (T-ALL) with: \r\n* Relapsed T-ALL with an M2 (blasts >= 5 to =< 25%) or M3 (> 25% blasts) marrow with or without an extramedullary site of relapse; including central nervous system (CNS) 2 OR\r\n* Refractory disease after induction failure of newly diagnosed patients OR no more than two more cycles of therapy OR\r\n* Refractory disease with no more than one prior salvage attempt following the current relapse
AML that is refractory to or relapsed after standard induction therapy.
Disease status defined as refractory to or relapsed after >=1 prior treatment lines.
Relapsed and/or refractory myeloma; there is no minimum or maximum number of previous therapies that a patient may have received previously before being put on the current trial
Relapsed/refractory disease, or inadequate response to at least 6 cycles of hypomethylating therapy. Subjects must not have received any MDS or MAL directed therapy for >28 days prior to receiving the study treatment.
Relapsed or refractory AML, who require salvage therapy
Relapsed and/or refractory disease on at least 1 prior treatment regimen, as follows:\r\n* Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 1 prior doxorubicin-containing regimen\r\n* Indolent B-cell lymphoma: relapsed after and/or refractory to at least 1 prior rituximab-containing regimen
Pathologically confirmed stage IV unresectable relapsed, or unresectable refractory abdominal neuroendocrine tumor from the last biopsy available which may be the initial diagnostic biopsy; relapsed disease is defined as progressive disease following systematic therapy with lanreotide or equivalent and either sunitinib or everolimus or both; refractory disease is defined as disease not responding to or having progressed within 1 month of the last dose of most recent systemic therapy to include lanreotide or an analog and either sunitinib or everolimus; (Note, small cell carcinoma and large cell undifferentiated neuroendocrine tumors will be excluded from this trial)
for subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT
Patients >= 18 years of age with relapsed/refractory Ph-positive ALL.
For patients with refractory disease they must be at least 4 weeks out from most recent therapeutic intervention
Diagnosis of R/R B-cell NHL or ALL as defined below:\r\n* Relapsed or refractory B-cell NHL meeting all of the following criteria:\r\n** Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; LBCL transformed from any indolent histology; or primary mediastinal B-cell lymphoma (PMBCL)\r\n** Prior treatment with an anthracycline and rituximab or another CD20-targeted agent (unless the disease is CD20-negative); transformed DLBCL (tDLBCL) must have failed treatment for DLBCL\r\n** At least one of the following:\r\n*** Refractory disease after frontline chemo-immunotherapy\r\n*** Not eligible for autologous hematopoietic stem cell transplant (auto-HSCT)\r\n*** Relapsed or refractory disease after at least 2 lines of therapy or after auto-HSCT\r\n*** Relapsed or refractory disease after allogeneic hematopoietic stem cell transplant (allo-HSCT)\r\n* Relapsed or refractory B-cell ALL (patients with Burkitt’s lymphoma/leukemia are not eligible)\r\n* All B-ALL patients must have detectable disease by morphology, flow cytometry, cytogenetic analysis (e.g. polymerase chain reaction [PCR], fluorescence in situ hybridization [FISH], karyotyping) or imaging (positron emission tomography [PET]-computed tomography [CT])\r\n** Refractory: failure to achieve complete response (CR) (minimal residual disease [MRD]-negative) at the end of induction\r\n** Relapsed: recurrence of disease after achieving CR
Patients must have CD19+ B cell malignancy with relapsed or refractory disease, defined as below:\r\n* Patients with chronic lymphocytic leukemia (CLL):\r\n** Refractory to or relapsed after at least 2 prior chemo or chemoimmunotherapy (e.g. fludarabine, cyclophosphamide, rituximab [FCR], bendamustine plus rituximab [BR]) requiring further treatment \r\n** Refractory to or relapsed after at least 1 prior biologic agent (e.g. ibrutinib, idelalisib, venetoclax, except a single agent anti-CD20 monoclonal antibody) requiring further treatment\r\n* Patients with indolent non-Hodgkin lymphoma (iNHL) (follicular lymphoma [FL], marginal zone lymphoma [MZL], Waldenstrom macroglobulinemia [WM]):\r\n** Refractory or relapsed after at least 2 lines of chemoimmunotherapy (including at least one course of anti-CD20 antibody)\r\n** Refractory or relapsed after at least 1 prior biologic agent (e.g. lenalidomide, ibrutinib, idelalisib)\r\n** Patients must have measurable disease (for WM patients, measurable disease is demonstrable monoclonal paraprotein and bone marrow involvement)\r\n* Patients with diffuse large B cell lymphoma (DLBCL), transformed B cell lymphoma, or high grade B cell lymphoma:\r\n** Refractory to or relapsed after 1 or more prior chemoimmunotherapies with at least one containing an anthracycline and CD20 directed therapy\r\n** Transplant ineligible\r\n** Biopsy proven relapsed disease\r\n* Patients with acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) in lymphoid blast crisis or Burkitt‘s lymphoma:\r\n** Refractory to at least 1 prior induction chemotherapy\r\n** Relapsed after at least 1 prior multiagent systemic chemotherapy that included induction and consolidation\r\n** Patients with Philadelphia chromosome-positive ALL must have failed a second generation tyrosine kinase inhibitor
Diagnosis of relapsed/refractory advanced malignancies; specifically:\r\n* Patients relapsed refractory acute myeloid leukemia that have failed at least one line of prior therapy, \r\n* Patients with myelodysplastic syndrome that have failed hypomethylating agents, \r\n* Patients with myelofibrosis that have failed or are ineligible to receive ruxolitinib\r\n* Patients that have myelofibrosis on maximal tolerated doses of ruxolitinib, who are unable to discontinue ruxolitinib, are eligible if;\r\n** They have been on stable dose for 1 month and continue to have residual symptoms, splenomegaly or inadequately controlled blood counts
Have relapsed, refractory, or progressive disease following last line of treatment
Relapsed or refractory disease after first-line chemoimmunotherapy
Relapsed or refractory B-cell NHL, including
Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC. Prior use of cisplatin (or carboplatin) is permitted.
Patients must have relapsed or refractory cancers for which there is no known curative option
Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments.
Part A: Relapsed or refractory extracranial solid tumors and (Phase 1b expansion) relapsed or refractory extracranial solid tumors with molecular alterations, non-gene fusions;
Part C: Relapsed or refractory neuroblastoma;
Patient must be either refractory to or relapsed after 1 line of therapy; prior radiation therapy is allowed
Patients must be either refractory to or relapsed after 1 line of therapy; exception: in the expansion cohort only, no BV refractory patients will be allowed
Relapsed/refractory disease
with relapsed or refractory disease without established alternative therapy or
Subjects must have a histologically determined B cell NHL subtype as defined in the bullets below. In addition, they must have disease that is primary refractory after initial therapy or have relapsed disease.
Relapsed within 1 year of first response
History of refractory systemic infection
Subjects with acute myeloid leukemia (AML) should have failed any prior induction therapy regimen or have relapsed after prior therapy (defined as patients in first relapse and less than 12 months from diagnosis [short first remission] or in second or later relapse; refractory defined as failure to achieve complete response [CR] to standard induction therapy, such as \7 and 3\, high dose ara-C-containing regimen or a hypomethylating agent): dose-escalation phase: subjects with confirmed relapsed or refractory AML and no available treatment options with known benefit; expansion phase: subjects with relapsed/refractory AML who have failed therapy with up to one prior salvage regimen and no available treatment options with known benefit; exception: stem cell transplant (SCT) or stem cell therapy for subjects who previously underwent SCT/stem cell therapy, and are currently in remission will not be considered a salvage regimen
PHASES 1 AND 2: patient participants with AML that has relapsed after, or is refractory to, first-line therapy, with or without subsequent additional therapy, and are currently considered unfit for, or unlikely to respond to, cytotoxic chemotherapy
Disease status defined as:\r\n* Patients with relapsed or refractory DLBCL that has relapsed post-transplant or that has been determined to be ineligible or unsuitable for transplant; patients must have to have received at least one prior systemic therapy
Patients with relapsed/refractory stage IIB-IV cutaneous T cell lymphoma who have received at least one standard systemic treatment such as extracorporeal photopheresis, bexarotene, or interferon
Relapsed, refractory, or recurrent malignancy; all solid tumor diagnoses will be eligible
Patients must be either refractory to or relapsed after 1 line of therapy
Patient must be either refractory to or relapsed after 1 line of therapy
All patients with histologically or cytologically confirmed relapsed or refractory AML (except acute promyelocytic leukemia); relapsed disease or refractory (refractory to a non-high-dose cytarabine-containing regimen only); receiving 1st, 2nd or 3rd salvage; any cytogenetic or molecular abnormality; patients with secondary AML (after prior myelodysplasia or therapy for other cancers) will be included
Patients must meet one of the following disease criteria within 24 months of registration; salvage therapy is allowed between the patient meeting one of the below criterion and registration; patients will be considered eligible regardless of their current disease status (i.e. complete remission, partial remission, stable disease, progressive disease) unless otherwise noted below as long as one of the below criterion has been met within the previous 24 months :\r\n* Relapsed/refractory Hodgkin lymphoma after autologous stem cell transplant (ASCT)\r\n* Relapsed/refractory Hodgkin lymphoma, deemed ineligible for ASCT due to refractory disease\r\n* Relapsed/refractory diffuse large B cell lymphoma after ASCT (history of transformed lymphoma is acceptable); disease must be in at least complete remission or partial remission with the use of salvage therapy before study treatment commences\r\n* Relapsed/refractory diffuse large B cell lymphoma, deemed ineligible for ASCT due to refractory disease (history of transformed lymphoma is acceptable); disease must be in at least complete remission or partial remission with the use of salvage therapy before study treatment commences\r\n* Relapsed/refractory T cell lymphoma relapsed after at least 1 prior line of therapy\r\n* Relapsed/refractory follicular lymphoma relapsed after at least 1 prior line of therapy\r\n* Relapsed/refractory mantle cell lymphoma relapsed after at least 1 prior line of therapy\r\n* Relapsed/refractory small lymphocytic lymphoma/chronic lymphocytic leukemia relapsed after at least 1 prior line of therapy\r\n* Relapsed/refractory non-Hodgkin lymphoma, if not specified above, relapsed after at least 1 prior line of therapy
Relapsed/refractory lymphoma after CTL019
Participants who are either refractory to or relapsed within 90 days of receiving a regimen containing a cumulative dose of greater than or equal to (>/=) 18 g/m^2 of cytarabine
Refractory to or relapsed after at least 1 prior treatment regimen
Have relapsed or refractory MM after at least one line of therapy
Relapsed disease after standard chemotherapy
Patients with malignancy that is suspected or proven to have progressed, relapsed, or be persistent since progressive, relapsed or persistent malignancy documented since BMT
PHASE II COMPONENT: The population will be restricted to relapsed/refractory sarcomas
Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease after at least 2 courses of chemotherapy.
Patients with recurrent/relapsed AA will be eligible for the trial as long as they were not previously refractory to hATG-based therapy and the relapse occurred > 3 months after response.
DTC participants must be 131 iodine-refractory/ relapsed as defined by at least one of the following:
Patients with previously treated B-cell ALL (relapsed and/or refractory after prior therapy)
Relapsed/refractory disease that has failed conventional therapy and other therapies of higher priority
Disease which has relapsed, or is refractory, following at least one line of therapy, with no therapy of higher priority available.
Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable by either surgery or radiation.
Burkitt’s or Burkitt-like leukemia/lymphoma, either previously untreated, or relapsed/refractory, or human immunodeficiency virus (HIV)-related; patients HIV positive will be described and reported separately or relapsed/refractory acute lymphoblastic leukemia (ALL)
Refractory disease (i.e. less than a partial response to frontline therapy)
Patients who are not candidates for, intolerant, or relapsed/refractory to ruxolitinib
Refractory to or relapsed after at least 1 prior treatment regimen
Relapsed/refractory MCL: Patient has relapsed and or refractory MCL and must have received at least one prior treatment regimen for their disease; patient with leukemia phase (peripheral blood involvement), leptomeningeal disease, cerebral spinal fluid (CSF) MCL, central nervous system (CNS) MCL, non-measurable disease, gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible
Relapsed/refractory MCL: Patients with bone marrow or gastrointestinal (GI) only involvement are acceptable
Relapsed/refractory MCL: The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient’s health and survival, than of the MCL, within the subsequent 6 months at the time of consent
Relapsed/refractory MCL: Prior treatment with ibrutinib
Relapsed or refractory AML
Relapsed or refractory to the most recently received therapy; refractory disease is defined as =< 25% response or progression during therapy or within 60 days after completion
Relapsed/refractory to at least one prior standard systemic treatment regimen, but no more than 4.
Refractory or relapsed and refractory multiple myeloma
Subject has measurable disease according to RECIST v1.1 and has relapsed or is refractory to prior therapy.
Relapsed disease
Primarily refractory or relapsed disease
Relapsed ALL PATIENT CHARACTERISTICS:
Patients with relapsed disease are eligible if they have had no more than one prior therapy
Biopsy-proven relapsed or refractory lymphomas; relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted > 6 months; refractory is no response or relapse within 6 months; previous biopsies < 6 months prior to treatment on this protocol will be acceptable\r\n* NOTE: Arms A/B – relapsed or refractory DLBCL within 24 months from the end of anthracycline-based therapy; no prior salvage therapy; patients can have received radiation therapy as part of initial treatment but not specifically for relapse\r\n* NOTE: Arm C patients include relapsed lymphoma patients of any type, other than those eligible for Arms A/B, for which the recommended treatment includes one of the platinum-based regimens; of note, relapsed double-hit high grade lymphoma patients and relapsed Hodgkin lymphoma patients will be enrolled in Arm C; there is no limit on the number of prior therapies for Arm C patients; the patient must be eligible for a platinum-based regimen and must not have received the same regimen in the past without responding
Patients with relapsed/refractory CMML.
Refractory to or relapsed after at least 1 prior treatment regimen
Refractory to first or later treatment, or
Pathologically confirmed relapsed or refractory (primary refractory and relapsed refractory) Acute Myeloid Leukemia (AML) (defined by World Health Organization (WHO) criteria) for which no further conventional therapy is suitable for the patient, or confirmed myelodysplastic syndrome defined according to WHO classification, with an International Prognostic Scoring System (IPSS) risk category of intermediate-2 or high risk, that is relapsed, refractory or intolerant to conventional therapy within 3 weeks of registration.
Patient must have a diagnosis of multiple myeloma and have relapsed or relapsed/refractory disease.
Histologically or cytologically confirmed diagnosis of multiple myeloma that is relapsed or relapsed-and-refractory after at least 2 or more prior lines of therapy. Patients must have achieved at least minor response (MR) to at least one prior line of therapy
Histological diagnosis of relapsed or refractory classical HL
Subjects must be primary refractory or relapsed to 1st line intensive treatment for AML or refractory or relapsed after second line of treatment for AML
Relapsed/refractory disease
The subject must have precursor B-cell or T-cell acute lymphoblastic leukemia. B-cell: relapsed or refractory after first or subsequent salvage therapy; or T-cell: relapsed or refractory with first remission duration less than or equal to 12 months in first salvage; or relapsed or refractory after first or subsequent salvage therapy
Patients with T cell and natural killer (NK) cell lymphomas must be refractory to, be intolerant of, have relapsed following, or have refused all standard life-prolonging therapies
Subjects with myeloma that is relapsed and/or refractory to KRd when used in combination defined as progression of disease while on therapy or within 60 days of completing therapy
Patients must have disease refractory to standard therapy or recurrent malignancy; patient’s current disease state must be one for which no known curative therapy is available; to be eligible for phase I study patients should have primary refractory or relapsed disease as evidenced by either:\r\n* Local or/and metastatic tumor recurrence or primary refractory tumor measurable on CT or magnetic resonance imaging (MRI) scans\r\n* Refractory persistent bone marrow disease with evidence of NB involvement of bone marrow in at least one site of biopsy\r\n* NB with metaiodobenzylguanidine (MIBG)-positive skeletal lesions (at least one site)\r\n* For sarcoma patients with resected pulmonary lesions pre-surgery CT scans demonstrating disease are required
Diagnosis of relapsed or refractory AML and not candidate for standard consolidation treatment after daunorubicin and cytosine arabinoside OR diagnosis of APL relapsed after tretinoin (ATRA) and arsenic trioxide therapy or APL with persisting or rising blasts, and no other comparable or satisfactory alternative therapy available (including patients not eligible for, or who have access to, investigational therapies via a clinical trial)
Patients with relapsed/refractory CLL defined as having received ?2 treatment regimens that included:
Phase I: Pathologically confirmed relapsed or refractory B cell lymphoma; must have relapsed after initial therapy; no restriction in number of prior lines of therapy
Phase II: Pathologically confirmed relapsed or refractory HL; no restriction in number of prior lines of therapy
Participant has a hematologic malignancy that is positive for MLLr as determined by fluorescent in situ hybridization (FISH) or reverse transcriptase (RT)-PCR, and disease meets at least one of the following criteria:\r\n* Relapsed after or is refractory to chemotherapy\r\n* Relapsed after hematopoietic stem cell transplantation (HSCT)\r\n* Relapsed or refractory secondary leukemia\r\n** Relapse is defined as reappearance of leukemia cells after the attainment of complete remission and refractory is defined as >= 5% blasts at the end of induction; patients that achieved MRD negative status followed by reappearance of blasts at less than 5% are eligible
AML has relapsed after, or is refractory to, first-line therapy, with or without additional subsequent therapy
Relapsed or refractory after at least 1 front-line therapy
Biopsy proven WM with relapsed/refractory symptomatic disease are eligible for\n             enrollment.
Medulloblastoma or PNET of childhood that has relapsed or become refractory to standard chemotherapy; patients with pineoblastoma are eligible
* Phase 2 (Part B): Patients with ALK+ relapsed or refractory neuroblastoma
* Phase 2 (Part C): Patients with ALK+ relapsed or refractory ALCL (excluding patients with primary cutaneous ALCL)
Relapsed, refractory, or progressive disease following at least 2 prior systemic therapies
Part B: Diagnosis of MM with relapsed or refractory disease with previous exposure to PI (e.g., bortezomib or carfilzomib), IMiDs (e.g., lenalidomide or pomalidomide), and daratumumab, and refractory (based on IMWG criteria) to their last line of therapy
Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
Relapsed or refractory Richter syndrome and has received ?1 previous treatment for RS.
Phase 2 expansion: Relapsed or refractory DLBCL
Relapsed or refractory pediatric B-cell ALL:
Has evidence of persistent or recurrent AML in the peripheral blood and/or bone marrow that is refractory to, or has relapsed from, their most recent prior line of treatment.
Has evidence of persistent or recurrent AML in the peripheral blood and/or bone marrow that is refractory to, or has relapsed from, their most recent prior line of treatment.
Must be relapsed or refractory after 1 or 2 prior therapies. For this protocol, relapsed is defined as progressive disease (PD) documented more than 60 days after last dose; refractory is defined as documented absence of hematologic response or hematologic progression on or within 60 days after last dose of prior therapy.
Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
T-ALL or T-LBL participants with relapsed/refractory disease.
Relapsed or refractory pediatric B-cell ALL.
For relapsed/refractory subjects only:
Subjects age ? 18 years with relapsed or refractory AML after ? 2 prior induction regimens, at least one containing anthracyclines
Documented refractory or relapsed and refractory multiple myeloma
Relapsed and refractory patients must have achieved at least a partial response to previous treatment with proteosome inhibitor or lenalidomide, or both, but progressed within 6 months, and were refractory to their last treatment
Refractory to or relapsed after at least 1 prior treatment line.
Follicular low-grade NHL: either treatment naïve (except for France) or relapsed or refractory following at least one prior treatment. In Part 1 Dose Escalation only, in addition to follicular NHL, marginal zone B cell lymphomas: either treatment naïve or relapsed or refractory following at least one prior treatment.
Histologically documented, CD20-positive, relapsed or refractory (defined as having relapsed within 6 months to the previous treatment) FL or DLBCL (including primary mediastinal large B-cell lymphoma [PMLBCL])
Male or female patients, ages 18 years or older with pathologically confirmed relapsed or refractory B-cell lineage NHL who have failed or are intolerant to established therapy, or for whom no other treatment options are available. Refractory or relapsed B-cell NHL (per World health Organization [WHO] Classification system)
Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment
relapsed and/or refractory disease
Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
have MCL that relapsed after or is refractory to (a) first-line combination chemotherapy with or without stem cell transplant and (b) at least 1 other locally available therapy
Subject who has documented active relapsed or refractory disease requiring therapeutic intervention.
Treatment Naive MCL patients requiring treatment with no exposure to prior therapies. Relapsed/Refractory patients defined as disease relapsed or been refractory to ? 1 prior therapies for MCL and requiring further treatment. Patient who discontinued any prior treatment for MCL for tolerability reasons can also be enrolled.
Subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles (full therapeutic dose) and must have been deemed as relapsed, refractory, or intolerant. Refractory is defined as progressing on-treatment or within 60 days of the last dose.
Relapsed or refractory with at least one (FL) or two (MCL), but not more than four, prior lines of antineoplastic regimens.
For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment
Relapsed, refractory or previously untreated CLL
For relapsed disease:
Patients with relapsed or refractory AML\r\n* Patients without a response after two cycles of a 10-day course of decitabine\r\n* Patients with primary refractory AML (persistent disease after standard induction with 7+3) or relapsed AML\r\n* Patients who have relapsed post-allogeneic transplant
Documented relapsed, refractory or progressive disease after treatment with systemic therapy and must not be Rituximab-refractory.
Need of treatment for relapsed, progressed or refractory disease as assessed by the investigator.
Part I: Subjects must have relapsed or refractory B cell NHL
Relapse or refractory disease after at least 1 systemic therapy
Dose Escalation: Patients with relapsed or refractory AML
Have active, relapsed or refractory Acute Myeloid Leukemia (AML). Active, relapsed or refractory AML is defined as either (1) primary induction failure (PIF) after 2 or more cycles of chemotherapy, (2 first early relapse after a remission duration of fewer than 6 months, (3) relapse refractory to salvage combination chemotherapy containing high-dose AraC, and (4) second or subsequent relapse
Patients refractory to ublituximab + TGR-1202
Relapsed or refractory B-precursor ALL defined as one of the following:
Relapsed or refractory disease after first or later salvage therapy
Relapsed or refractory CLL patients must meet the following requirements:\r\n* Received at least 1 prior therapy\r\n* Require treatment in the opinion of the investigator\r\n* Relapsed patients must have developed progressive disease following a response to a prior therapy\r\n* Refractory patients must have failed to respond or relapsed within 6 months to the last prior therapy
Histologically confirmed AML (defined using World Health Organization [WHO] criteria) with one of the following:\r\n* Primary refractory disease following =< 2 cycles of induction chemotherapy, or\r\n* First relapse with no prior unsuccessful salvage chemotherapy, or\r\n* Relapsed or refractory to hypomethylating agent, defined as a lack of response, disease progression, loss of response, or intolerance as deemed by the study investigator
Relapsed refractory disease after at least 1 but not more than 4 lines of previous systemic therapy
Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
Active refractory or relapsed acute leukemia
Patients with relapsed and refractory multiple myeloma who have received at least 2 prior therapies, which must include lenalidomide and a proteasome inhibitor; patients must have disease refractory to the most recent therapy; refractory myeloma is defined as progressive disease during or within 60 days of last therapy; patients must have previously received or be ineligible for (or refused) autologous stem cell transplant
Patient has relapsed or relapsed/refractory multiple myeloma (MM);\r\n* Relapsed is defined as the development of disease progression following the achievement of stable disease (SD) or better to the most recent anti-MM regimen\r\n* Refractory is defined as experiencing less than a partial response (PR) to or progressive disease (PD) within 6 months after completion of the most recent anti-MM regimen
Subject has relapsed/refractory disease with an indication for treatment
Patients must have a diagnosis of relapsed or relapsed and refractory multiple myeloma with a minimum of one prior regimen and a maximum of 5 prior regimens
Relapsed or refractory disease
Patients with relapsed or refractory AML
Relapsed after, or refractory to, prior BTK inhibitor therapy.
Multiple myeloma that is primary refractory or relapsed and refractory after at least 2 lines of standard for multiple myeloma including: a. > 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone or in combination) i. Patients who received bortezomib as their last therapy who were not refractory but developed bortezomib intolerance, as defined by the development of Grade 2 peripheral neuropathy with pain or > Grade 3 peripheral neuropathy after ? 2 consecutive cycles, are eligible b. Adequate alkylator therapy defined as: i. High-dose melphalan or other alkylating agent as conditioning for autologous or allogeneic stem cell transplant (SCT), or ii. ? 6 cycles of induction therapy, or iii. PD after ? 2 cycles
Patients must have relapsed or refractory disease following frontline chemotherapy; no upper limit for the number of prior therapies; patients may have relapsed after prior autologous or allogeneic stem cell transplant
Must have a documented diagnosis of multiple myeloma and have relapsed-and-refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease (SD) for at least one cycle of treatment to at least one prior regimen and then developed progressive disease (PD). Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
Disease that has relapsed or was refractory after prior chemo-immunotherapy
Patients must have relapsed or relapsed and refractory disease after receiving 2 or more lines of therapy\r\n* Relapse is the occurrence of any of the following: 1) > 25% increase in in myeloma protein (M-protein) from the baseline levels; 2) reappearance of M-protein that had disappeared; or 3) definite increase in the size and number of lytic bone lesions recognized on radiographs (compression fractures per se do not constitute a relapse)\r\n* Subjects will be considered refractory to therapy, as defined by progression during treatment or within 60 days after the completion of salvage treatment; subjects with primary refractory disease, defined as disease that is non-responsive in patients that have never achieved a minor response or better with any therapy are excluded; this includes: 1) non-responding, non-progressing; patients who never achieve minor response (MR) or better in whom there is no significant change in M protein and no evidence of clinical progression; and 2) progressive; primary refractory, progressive disease where patients meet criteria for true progressive disease
Histologically documented relapsed or refractory (defined as having relapsed within 6 months to the previous treatment) follicular lymphoma grade I-IIIA
Histologically or cytologically proven SCLC that has relapsed or been refractory after at least one line of chemotherapy
Refractory to or relapsed after at least 1 prior treatment regimen;
Patients must have either (1) refractory or relapsed high-risk NB (including n-myc proto-oncogene [MYCN]-amplified stage 2/3/4/4S of any age and MYCN-non amplified 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
Relapsed or refractory after ? 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have received Rituximab and alkylating agents.
Relapsed or relapsed/refractory progressive Multiple Myeloma
Relapsed or Relapsed/Refractory MM with progressive disease (PD) according to IMWG.
Was refractory to lenalidomide or proteasome inhibitor-based therapy at any line. NOTE: Refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy. Participants who progressed after 60 days from the last dose of a given therapy were considered relapsed and were eligible for inclusion in the study. Participants who were refractory to thalidomide-based therapy were eligible.
Patients must have relapsed or progressed after at least one prior therapy
Patients with relapsed or refractory disease following stem cell transplantation are permitted
Must have relapsed or refractory disease (refractory is defined as progression during treatment or within 60 days after the completion of treatment) requiring 2nd or 3rd line therapy
Patient was not refractory
Subjects must be relapsed/refractory. Prior stem cell transplantation is allowed.
Chemo-refractory is defined as:
B-cell CLL: Relapsed from or refractory to ? 2 prior lines of treatment, ? 1 of which must have contained rituximab
Relapsed or refractory B-ALL, defined as:
Subjects with histologically confirmed relapsed or treatment refractory AML with the exception of subjects who are in first relapse following a remission >12 months in duration and are eligible for standard therapies (e.g., chemotherapy or stem cell transplantation).
Relapsed or refractory AML
Relapsed or refractory to hypomethylating agents
Relapsed/refractory disease failing >= 2 prior therapies; an exception is patients with KS, where patients can be previously untreated, relapsed/refractory to one or more prior therapies, or intolerant of a prior therapy
Patients must have relapsed or refractory MCL
have one of the following disease states: Acute Myeloid Leukemia (AML) (age <60 years) with relapsed/refractory disease; •Chronic Lymphocytic Leukemia (CLL) with relapsed disease following a fludarabine-based regimen or relapsed disease following an alkylator-based regimen
Patients with previously treated ALL (relapsed and/or refractory after prior therapy); patients with relapsed/refractory biphenotypic leukemia expressing the appropriate antigen (CD22) are also eligible to participate; pediatric patients younger than 18 may be considered with sponsor approval once the MTD has been established in the adult population
Patients must have progressive, relapsed or refractory disease after:\r\n* At least one prior systemic anti-lymphoma regimen (chemotherapy or immunotherapy except for transformed mycosis fungoides as described previously)\r\n* Relapsed or failed autologous or allogeneic stem cell transplant
Subject must be either resistant to or intolerant of (ie., treatment failures) the last BCR PI and/or venetoclax. Resistant is defined as relapsed or refractory per
Chemotherapy-refractory disease, defined as one of more of the following:
Relapsed, refractory, or progressive disease following at least 2 prior systemic therapies
Adults with pathologically confirmed, relapsed or refractory acute myelogenous leukemia OR those 70 and older who are not candidates for, or decline, conventional frontline chemotherapy
Relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) demonstrated by cranial MRI.
Patients must have relapsed or refractory disease following:
Patients must have measurable disease according to RECIST 1.1, and have relapsed or become refractory to conventional therapy
Relapsed/refractory MDS
Diagnosis of AML or ALL, relapsed or refractory after at least 1 prior treatment regimen. Newly-diagnosed patients ? 60 years old who have refused or are considered unfit for standard chemotherapy regimens or stem cell transplantation are also eligible.
Patients must have relapsed or relapsed and refractory multiple myeloma (MM) after at least three but not more than six prior therapeutic regimens for MM, including induction therapy and stem cell transplant in candidate patients, which will be considered as only one regimen.
Participant’s disease has relapsed after, is refractory to induction and/or salvage therapy, or has relapsed after hematopoietic stem cell transplant (HSCT)
Patients with relapsed/refractory AML regardless of cytogenetic risk
Patients with relapsed/refractory ALL
Patients may not have received any anti-cancer therapy for their primary relapsed (rel)/refractory (ref) DLBCL with the exception of palliative radiation therapy (RT)
Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria, and have relapsed or become refractory to conventional therapy
Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up to second consecutive salvage . Relapsed subjects including first and second relapse.
Relapsed (progressed after prior response) or refractory (failed to achieve at least a partial response) to at least one prior therapy for amyloidosis.
Relapsed, refractory, or progressive disease following at least 1 prior systemic therapy. Patients with DLBCL or follicular lymphoma Grade 3 must have also received intensive salvage therapy.
Adult patients must be relapsed or refractory to at least 1 prior multi-agent systemic therapy. Pediatric patients must be relapsed or refractory to at least 2 prior multi-agent systemic therapies. Patients with acute lymphoblastic leukemia who are Philadelphia chromosome-positive must have failed a second generation tyrosine kinase inhibitor.
Clinical diagnosis of relapsed/refractory B-cell Malignancies (B-Non-Hodgkins Lymphoma (NHL)) per International Workshop Group (IWG)
Subjects in Expansion cohorts are restricted to relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Follicular Lymphoma (FL) subjects who are either relapsed or refractory to prior rituximab or ritxumab-containing chemotherapy regimens
Refractory to the most recently received therapy; refractory disease is defined as =< 25% response or progression during therapy or within 60 days after completion of therapy
Patients must have relapsed or refractory disease after ?1 prior line of treatment.
Patient has relapsed or refractory disease and received at least one prior therapy.
Patients with relapsed /refractory AML, ALL, or MLL with rearrangement of the MLL gene, including 11q23 or PTD, are eligible for the expanded cohort:
Patient has relapsed or relapsed/refractory multiple myeloma (MM)\r\n* Relapsed is defined as the development of disease progression following the achievement of stable disease (SD) or better to the most recent anti-MM regimen\r\n* Refractory is defined as experiencing less than a partial response (PR) to or progressive disease (PD) within 6 months after completion of the most recent anti-MM regimen
Patients with relapsed or refractory myeloma who have had >= 3 lines of prior therapy
Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
B1: Refractory or relapsed neuroblastoma
Relapsed/refractory, pathologically confirmed EBV+ lymphoid malignancy or lymphoproliferative disease
Participants must have relapsed or refractory cancer.
Part I: Patients with one of the following histologically- or cytologically-proven conditions: relapsed/refractory AML, relapsed/refractory MDS, or advanced CML in AP or BP (i.e., Acute Group patients).
Arm A: Patients with AML who are 65 years of age or older with refractory or relapsed disease, or who have not received prior therapy but are not eligible to receive intensive frontline chemotherapy (i.e., Acute Group patients);
Relapsed or refractory AML with poor prognostic features
Participants diagnosed with any relapsed or refractory CD30+ hematologic malignancy (e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study
Relapsed disease after standard 1st line therapy for aggressive lymphoma - not eligible for high dose chemotherapy with stem cell support. Relapsed or refractory disease after two lines of therapy one of which could have included Autologous Stem Cell Transplant (ASCT). Relapsed disease is defined as progression after a disease free interval of at least 6 months after completion of last therapy. Refractory is defined as progression of disease during prior therapy or within 6 months from its completion.
Relapsed is defined as experiencing PD that requires therapy but which is not refractory following the achievement of stable disease (SD) or better to the most recent anti-MM regimen.
Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
Previously treated relapsed or refractory B-cell iNHL
Diagnosis of relapsed or refractory chronic lymphocytic leukaemia.
Documentation of at least one line of prior myeloma therapy now with relapsed or refractory disease requiring re-treatment
Patients with relapsed or refractory systemic ALCL who have previously received front line chemotherapy.
Patients with relapsed/refractory AML regardless of cytogenetic risk
Patients with relapsed/refractory ALL
Patients with relapsed or persistent malignancy requiring immunosuppressive withdrawal or modulation (an example of this may be a patient who relapsed and was being treatment with DLI and then developed GvHD)
Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ? 1 cycle. Refractory disease is defined as ? 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy.
Relapsed/refractory myeloma
Expected chronic thrombocytopenia in patients with relapsed or refractory hematological malignancies or;
Relapsed/refractory disease within a prior radiation field
Relapsed or refractory to greater than or equal to (>=) 2 prior lines of chemotherapy based on standard of care with certain requirements for prior therapy.
Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available.
Phase II: Participants must have a diagnosis of AML and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)\r\n* Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy\r\n* Patients are eligible at first or subsequent relapse or any relapse that is refractory to salvage chemotherapy
Subjects who have relapsed or refractory MDS.
Participants who are refractory or relapsed after at least 1 prior line of therapy and for whom no effective standard therapy is available per the investigator's assessment.
Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
Patients with a relapsed and/or refractory underlying hematologic malignancy
Disease Status: Refractory or first or multiple relapsed neuroblastoma, or medulloblastoma that has relapsed after, or is refractory to, a chemotherapy-containing treatment regimen.
Subjects disease must have relapsed or be refractory to at least 2 prior lines of therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline.
Relapsed or is refractory to previous therapy, or
Relapsed/persistent malignancy
Relapsed/Refractory Cohorts: Pathologically confirmed relapsed or refractory (primary refractory and/or relapsed refractory) AML or confirmed intermediate, high, or very high risk MDS that is relapsed, refractory or intolerant to conventional therapy
Patients are relapsed from or refractory to at least 1 previous line of therapy
Patients must have had evidence of having relapsed, progressed or become refractory to conventional therapy
Refractory or relapsed after at least 1 prior line of therapy for whom no effective standard therapy is available per investigator's assessment. • Participants who are either treatment-naive to, relapsed after, or refractory to ibrutinib, idelalisib, or any other investigational B cell receptor (BCR) pathway inhibitors not directly targeting spleen tyrosine kinase (SYK) are allowed.
Participants who are relapsed after or refractory to regimens containing venetoclax or other BCL2 inhibitors.
Chemotherapy-refractory disease, defined as one or more of the following:
Patients with relapsed or refractory disease with no available standard therapy