First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C): No evidence of isolated extramedullary relapse (i.e., testicular or central nervous system [CNS])
ELIGIBILITY CRITERIA - PHASE II (ARM D): No evidence of isolated extramedullary relapse (i.e., testicular or CNS)
Subjects may not have presence of active CNS disease or extramedullary disease.
Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
PHASE I: If relapse/refractory status with no prior history of allogeneic HCT (one of the following)\r\n* 2nd or greater marrow relapse, with or without extramedullary disease\r\n* 1st marrow relapse at end of 1st month of re-induction with marrow having\r\n* >= 0.01% blast by morphology and/or MPF, with or without extramedullary disease\r\n* Primary refractory as defined as having M2 or M3 marrow after 2 or more separate induction regimens\r\n* Subject has indication for HCT but has been deemed ineligible
PHASE II: Confirmed CD19+ leukemia recurrence defined as >= 0.01% disease in the marrow or isolated extramedullary disease following allogeneic HCT OR
PHASE II: No prior history of allogeneic HCT (one of the following)\r\n* 2nd or greater relapse, with or without extramedullary disease (isolated extramedullary disease is eligible)\r\n* 1st marrow relapse at end of 1st month of re-induction with marrow having >= 0.01% blast disease, with or without extramedullary disease\r\n* Primary refractory as defined as having M2 or M3 marrow after induction\r\n* Subject has indication for HCT but has been deemed ineligible OR
Extramedullary disease status: patients with isolated CNS disease or isolated testicular disease are not eligible
Patients with extramedullary disease only are eligible
Isolated extramedullary disease
Subjects who have received prior radiation therapy for extramedullary disease within 2 weeks of first dose
Patients with active extramedullary disease.
Patients with extramedullary disease as their sole site of relapsed AML.
Patients with isolated extramedullary disease or with known parenchymal central nervous system (CNS) disease
No evidence of disease-related symptoms and extramedullary disease, including the liver and spleen
Isolated extramedullary leukemia without also meeting bone marrow criteria for leukemia
A histologically or pathologically confirmed diagnosis of AML based on WHO classification with or without extramedullary disease except for central nervous system disease.
Participants with extramedullary AML with no evidence of systemic involvement
Isolated extramedullary relapse (i.e. testicular, central nervous system)
PHASE II ONLY: Isolated extramedullary relapse
Solitary bone or extramedullary plasmacytoma disease only
No active extramedullary leukemia or known active CNS involvement by malignancy; such disease treated into remission is permitted
Extramedullary leukemia allowed except CNS disease
Extramedullary (CNS) disease;
Patients with known extramedullary leukemia are not eligible
Patients with isolated extramedullary disease or with parenchymal central nervous system (CNS) disease
Patients with isolated central nervous system (CNS), testicular, or other extramedullary site of relapse
Patient must have one of the following:\r\n* Recurrent disease with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease.\r\n* Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease
Disease status: \r\n* Phase 1 (Part A):\r\n** Patients must have either measurable or evaluable disease \r\n* Phase 2 (Part B):\r\n** Ewing sarcoma or peripheral PNET: patients must have measurable disease\r\n* Phase 2 (Part C):\r\n** Acute lymphoblastic leukemias (ALL): patients with ALL must have an M3 marrow with or without extramedullary site of relapse OR an M2 bone marrow with an extramedullary site of relapse; patients with CNS 3 status are not eligible for enrollment
Isolated extramedullary relapse (i.e., testicular, CNS).
Patients must be in morphologic leukemia-free state (marrow blasts < 5%) without evidence of extramedullary disease within 21 days of HCT
Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cells dyscrasia
Extramedullary disease only.
Isolated extramedullary disease
Patients may have CNS or other sites of extramedullary disease; no cranial irradiation is allowed during the protocol therapy
Isolated extramedullary disease relapse
Isolated extramedullary relapse (leukemia) or isolated CNS lymphoma
Active extramedullary disease at any site. (Note: Definitive therapy of known previous sites of extramedullary disease is allowed)
Isolated extramedullary relapse (i.e., testicular or CNS)
Isolated extramedullary disease (leukemia)
Multiple myeloma: solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
Patient must have relapsed/refractory acute lymphoblastic leukemia (ALL) with ? 5 blasts in the bone marrow or biopsy confirmed extramedullary disease. Patient may have CNS 1, 2 or 3 disease. Isolated CNS relapse is not eligible.
Isolated extramedullary disease
Isolated extramedullary disease
Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
Active extramedullary disease
Extramedullary disease in the absence of bone marrow or blood involvement
Extramedullary disease in the absence of any measurable medullary involvement
Patients with known extramedullary leukemia
Extramedullary disease only
Active leukemia in the testes or isolated extramedullary relapse; patients with a history of treated leukemia in testes but no active disease at the time of enrollment are eligible
Isolated extramedullary relapse.
AML patients in first complete remission (CR) (CR1) or first complete remission with incomplete blood count recovery (CRi) after induction and consolidation chemotherapy; except young (< 60 years) AML patients in European LeukemiaNet favorable group; (the current trial will exclude young favorable group AML patients), patients could receive any cycle consolidation or no consolidation per the discretion by the treating physician
Patients must have achieved a radiologic complete or partial remission as defined by the Lugano criteria
Prior or concurrent malignant disease unless in complete remission for more than five years
Mantle cell NHL: may be treated in first complete remission (CR); (diagnostic lumbar puncture [LP] required pre-transplant)
Biopsy-proven intermediate or high-grade non-Hodgkin’s lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment):\r\n* In partial remission\r\n* Relapsed after initial complete remission\r\n* Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease)\r\n* In complete remission with high-risk features as specified by the International Prognostic Index
Biopsy-proven Hodgkin’s lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment)\r\n* In first, or greater relapse after initial complete remission\r\n* In partial remission\r\n* Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease)
Biopsy-proven Burkitt’s lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment):\r\n* In second complete remission after relapse following initial complete remission\r\n* Failed induction therapy, but responds (very good partial remission, complete remission, or near complete remission) to salvage therapy (i.e., chemosensitive disease)
NOTE: Patients meeting the following criteria are exempt from the 8 month timeline and do not require additional biopsy:\r\n* Patients who have never achieved a complete remission on the last biopsy-proven site of disease and went on to the next therapy then achieved a complete remission\r\n* Patients who relapsed quickly (within 3 months of their last chemotherapy) and now have achieved a complete remission with salvage therapy
Complete first remission (CR1) at high risk for relapse
Complete second remission (CR2).
Complete first remission (CR1) at high risk for relapse
Complete second remission (CR2).
Any remission after chimeric antigen receptor (CAR)-T cell therapy
Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following: Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other Mixed Lineage Leukemia (MLL) rearrangements; White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL)at diagnosis; Recipient age older than 30 years at diagnosis; Time to CR greater than 4 weeks
AML that has failed to achieve complete remission or morphologic complete remission or
History of at least one anti-CD20 antibody containing regimen that resulted in initial measurable response (partial or complete remission), followed by relapse/recurrence.
Histologic diagnosis of malignant melanoma, stages IIB-IV is radiologically confirmed complete clinical remission (cCR) without clinical evidence of disease
Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:\r\n* All patients must be in CR as defined by < 5% blasts by morphology; flow cytometry in a representative bone marrow sample with cellularity >= 15% for age; patients who do not have high-risk disease (high risk CR1, greater than one cycle to obtain CR or >= CR2) must be discussed with the PI prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative\r\n* Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator Ann Dahlberg prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
For AML: patients must belong to one of the following ‘high risk’ categories: \r\n* Primary induction failure (PIF) as defined by failure to achieve at least a 50% reduction in bone marrow blasts after one cycle of high intensity, anthracycline containing induction regimen or failure to achieve complete response (CR)/complete remission with incomplete blood count recovery (CRi) after two cycles of high intensity chemotherapy\r\n* First early relapse as defined by an initial remission duration of fewer than 6 months\r\n* Second or subsequent relapse regardless of remission duration, or\r\n* Relapse after allogeneic or autologous stem cell transplantation (first relapse after stem cell transplant would be eligible, regardless of prior duration of remission)
Patients with newly diagnosed, previously untreated B-lineage ALL, or having achieved complete remission (CR) with one course of induction chemotherapy
Patients with B-lineage ALL in hematologic complete remission (CR) with molecular failure (ie, had never achieved an MRD-negativity status before inotuzumab ozogamicin) or had a molecular relapse (i.e., became MRD positive after having been MRD negative) starting at any time point after 3 months of frontline therapy. Molecular disease or minimal residual disease is defined by a value of at least of 10^-4 by multicolor flow cytometry
Acute lymphoblastic leukemia (ALL):\r\n* Complete first remission (CR1) at high risk for relapse such as any of the following:\r\n** White cell count at presentation > 30,000 for B-cell lineage and > 100,000 for T-cell lineage.\r\n** Presence of any high-risk cytogenetic abnormalities such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality.\r\n** Failure to achieve complete remission after four weeks of induction therapy.\r\n** Persistence or recurrence of minimal residual disease on therapy.\r\n** Any patient with newly diagnosed ALL >= 50 years-old.\r\n** Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.\r\n** Other high risk features not defined above.\r\n* Complete second remission (CR2).\r\n* Primary refractory or relapsed ALL with less than 5% blasts before transplant. Persistent/relapsed ALL with cytogenetic, flow cytometric or molecular aberrations in >= 5% of cells are eligible.
First relapse if first remission ? 12 months
Patients with the following hematologic malignancies:\r\n* Acute myelogenous leukemia (AML): High-risk AML including:\r\n** Antecedent hematological disease (e.g., myelodysplasia [MDS])\r\n** Treatment-related leukemia\r\n** Complete remission (CR1) with poor-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, complex cytogenetics)\r\n** CR2 or CR3\r\n** Induction failure or 1st relapse with =< 10% blasts in the marrow\r\n* Acute lymphoblastic leukemia (ALL)\r\n** High-risk CR1 including:\r\n*** Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22) or 11q23 rearrangements)\r\n*** Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy\r\n** No CR within 4 weeks of initial treatment\r\n** Induction failure with =< 10% blasts in the marrow\r\n** CR2 or CR3\r\n* Myelodysplastic syndromes (MDS), intermediate, high or very high risk by the revised international prognostic scoring system (IPSS-R)\r\n* Chronic myelogenous leukemia (CML) in second chronic phase after accelerated or blast crisis\r\n* Myelofibrosis (MF):\r\n** Intermediate-2 or high risk by Dynamic International Prognostic Scoring System (DIPSS)-plus OR\r\n** Monosomal karyotype OR\r\n** Presence of inv(3)/i(17q) abnormalities OR\r\n** Other unfavorable karyotype OR leukocytes >= 40 x 10(9)/L AND\r\n** Circulating blasts =< 9%\r\n* Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma, Hodgkin lymphoma) meeting the following criteria:\r\n** Disease status: Stable disease, partial remission or 2nd and 3rd complete remission\r\n** Have relapsed after autologous transplant or who have failed to collect for an autologous transplant
Relapsed or refractory (resistant) disease, as defined by standard criteria\r\n* Relapsed: Bone marrow blasts >= 5%, reappearance of blasts in the blood, or development of extramedullary disease following achievement of complete remission (CR)/complete remission with incomplete recovery of blood counts (CRi)/complete remission with incomplete recovery of platelets (CRp)/morphologic leukemia free state (MLFS)\r\n* Refractory (resistant): Failure to achieve CR/CRi/MLFS in subjects who survive >= 7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
Mantle cell NHL-may be treated in first complete remission (CR); (diagnostic lumbar puncture [LP] required pre-transplant)
For B-ALL\r\n* Chemotherapy refractory disease in subjects with B-ALL is defined as progression or stable disease after two lines of lines of therapies\r\n* Recurrence of disease after achieving complete remission (CR)\r\n* Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, polymerase chain reaction [PCR], fluorescence in situ hybridization [FISH], or next generation sequencing) require verification of MRD positivity on two occasions at least 4 weeks apart\r\n* Subjects with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs)\r\n* Subjects with recurrence of isolated central nervous system (CNS) relapse after achieving complete remission (CR); if relapsed with MRD, will require verification of MRD positivity on two occasions at least 4 weeks apart
Patients in partial or complete remission following cell therapy will also be eligible
Lymphoblastic lymphoma\r\n* All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)\r\n* Patients with any high-risk features will be eligible in first complete remission\r\n* High risk features include:\r\n** Stage IV\r\n** Lactate dehydrogenase (LDH) > 2 x upper limit of normal\r\n** >= 2 extranodal sites
PHASE I: Patients who have/are either:\r\n* Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation\r\n** Pre- or post-transplant minimal residual disease defined by:\r\n*** Any detectable acute lymphocytic leukemia (ALL) (by flow cytometry, cytogenetics, or polymerase chain reaction [PCR] techniques) as per clinical indication\r\n* In second or third complete remission at the time of allogeneic transplantation\r\n* Treated with reduced intensity regimens\r\n* Lymphoid blast crisis of chronic myelogenous leukemia (CML)\r\n* Are relapsed or refractory to at least 1 line of chemotherapy
PHASE II: Patients who have/are either:\r\n* Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation\r\n** Post-Transplant Minimal Residual Disease defined by:\r\n*** Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication\r\n* In second or third complete remission at the time of allogeneic transplantation\r\n* Treated with reduced intensity regimens\r\n* Lymphoid blast crisis of CML\r\n* Are relapsed or refractory to at least 1 line of chemotherapy
Acute lymphocytic leukemia (ALL) in complete remission (CR)1 with high-risk features including adverse cytogenetic such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; in second or greater morphologic remission; persistent minimal residual disease
Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease and persistent detectable minimal residual disease (MRD), or with high-risk features defined as: greater than 1 cycle of induction therapy required to achieve remission; preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; presence of FLT3 mutations or internal tandem duplications, DNMT3a, TET2, MLL-partial tandem duplication (PTD), ASXL1, PHF6; FAB M6 or M7 classification; adverse cytogenetics including: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8, complex [> 3 abnormalities]
Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high risk for relapse including:\r\n* t(9;22) or detected BCR-ABL1 translocation by genomic methodologies\r\n* BCR-ABL1-Like B-ALL including mutations of IKZF1 or CRLF2\r\n* Translocations or mutations involving 11q23 (MLL) gene\r\n* Hypodiploid karyotype\r\n* Deletion of 9p\r\n* Loss of 17p or TP53 mutation\r\n* T-lymphocyte lineage antigen expression (T-ALL)\r\n* Central nervous system (CNS) or other extramedullary involvement\r\n* White blood cell (WBC) count >= 100,000 cells/uL at diagnosis
Patients with newly diagnosed, previously untreated B-lineage ALL or lymphoblastic lymphoma, or having achieved complete remission (CR) with one course of induction chemotherapy; patients who require steroids, cytarabine (ara-c) or hydrea to manage disease symptoms prior to finalization of diagnosis and treatment plan are allowed and eligible
Response to therapy and completion of at least one cycle of consolidation therapy, and with disease status meeting one of the following criterion at the time of post-induction disease restaging:\r\n* Minimal residual disease, as defined by detectable disease by flow cytometry but with marrow that is at least 10% cellular with < 5% blasts on morphologic review\r\n* Complete remission with incomplete blood count recovery (CRi)/complete remission with incomplete platelet recovery (CRp), as defined by absence of detectable disease by flow cytometry, and marrow that is at least 10% cellular with < 5% blasts on morphologic review, but with neutrophil count < 1000/ul (CRi) and/or platelet count < 100,000/ul (CRp); in pediatric patients, a platelet threshold of < 80,000/ ul will be used, as per consensus pediatric response criteria
In a morphologic complete remission with incomplete blood count recovery, or morphologic complete remission post-induction after no more than 2 induction cycles
Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics including complex karyotype, abnormal [abn][3q], -5/5q-, -7/7q-, abn[12p], abn[17p], myeloid/lymphoid or mixed-lineage leukemia [MLL] gene re-arrangement and t [6;9]47, fms related tyrosine kinase 3 [flt3] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndromes (MDS), any disease beyond first remission
Acute lymphoblastic leukemia (ALL): Induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); relapsed double hit lymphomas; patients with options for treatment that are known to be curative are not eligible
Plasma Cell Leukemia after initial therapy if achieved at least in partial remission; or relapsed and achieved subsequent remission (CR/PR)
Have a newly diagnosed AML, based on World Health Organization criteria, currently in first (1st) complete remission (CR)/complete remission with incomplete count recovery (CRi) on a bone marrow biopsy performed within 4 weeks of study enrollment
Patient relapsing more than 2 years after initial remission
Very high risk pediatric patients with ALL: Patients < 21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction; they are eligible once they achieved a complete remission
History of malignant tumors other than KS or KSHV-MCD, unless:\r\n* In complete remission for >= 1 year for the time complete remission was first documented\r\n* Resected basal cell or squamous cell carcinoma of the skin\r\n* In situ cervical or anal dysplasia
Hematologic Malignancy\r\n* No human leukocyte antigen (HLA) identical sibling or suitable unrelated donor, or time needed to find an acceptable unrelated donor match would likely result in disease progression such that the patient may become ineligible for any type of potentially curative transplant\r\n* Relapsed or primary therapy-refractory acute myeloid leukemia (AML) with bone marrow blast < 20%\r\n* High-risk refractory or relapsed acute lymphoblastic leukemia (ALL) in patients for whom transplantation is deemed indicated (relapse occurring < 30 months from diagnosis, patients relapsing after previous allogeneic transplant, relapse after 2nd remission, primary induction failure or hypodiploidy)\r\n* Patients with relapsed Hodgkin lymphoma unable to achieve 2nd remission or very good partial remission (VGPR) and therefore ineligible to receive autologous stem cell transplantation\r\n* Patients with Hodgkin lymphoma relapsing after autologous stem cell transplant\r\n* Patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL) unable to achieve 2nd remission or very good partial remission (VGPR) and therefore ineligible to receive autologous stem cell transplantation\r\n* Patients with NHL relapsing after autologous stem cell transplant\r\n* Patients with myelodysplastic syndrome (MDS)/myeloproliferative syndrome (MPS)
Solid Tumor\r\n* Failed or ineligible to receive autologous transplant or if autologous transplant would not offer > 20% chance of cure\r\n* Neuroblastoma\r\n** High risk with relapsed or refractory disease\r\n* Soft tissue sarcoma (rhabdomyosarcoma, Ewing sarcoma, primitive neuroectodermal tumor, or other high-risk extracranial solid tumors)\r\n** Relapsed or primary refractory metastatic\r\n** 1st complete remission, but very high-risk features (i.e., < 20% survival with conventional therapy)\r\n* Osteosarcoma\r\n** Failure to achieve complete remission (CR) following initial therapy\r\n** Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery and/or chemotherapy
Patients must be in a >= 2nd complete remission as indicated by appropriate radiologic evaluations at the time of study entry
Patients with OS in first complete remission
Patients with B-lineage acute lymphocytic leukemia (ALL) in hematologic complete remission (CR) with molecular failure (ie, had never achieved an MRD-negativity status before blinatumomab) or had a molecular relapse (ie, became MRD positive after having been MRD negative) starting at any time point after 3 months of frontline therapy; molecular disease or minimal residual disease is defined by a value of at least of 1 x 10^-4 by multicolor flow cytometry
Patients likely to have a significantly better durable response to allogeneic transplant alone (better than 60% progression free longer than 2 years) includes: those with myeloproliferative diseases or hemoglobinopathies with over 50% T cell subset engraftment (assessed around 100 days post transplant); it is not anticipated that any such patients would be transplanted within our program, however but those in first remission acute myeloid leukemia (AML) patients with good risk standard genetics or normal genetics with either nucleophosmin (NPM)1 or CCAAT/enhancer binding protein alpha (CEBPA) mutations, first chronic phase chronic myelogenous leukemia (CML) without kinase gene mutations, follicular lymphoma patients in first remission who only required 1 regimen to attain remission all would be excluded from this protocol
Eligible patients will have a histopathologically confirmed diagnosis of hematologic malignancy in one of the following categories: \r\n* Acute myelogenous leukemia \r\n** In first complete remission (CR1) with poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (AML): monosomal karyotype, -5, 5q-,-7,7q-,11q23-non t(9;11), inv (3), t(3;3), t(6;9), t(9;22) and complex karyotypes (>= 3 unrelated abnormalities [abn]) and normal cytogenetics with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplications (ITD) mutation \r\n** In second complete remission (CR2) or third complete remission (CR3) \r\n** With chemosensitive primary refractory disease \r\n* Acute lymphocytic leukemia \r\n** In CR1 with poor risk cytogenetics: \r\n*** For adults according to NCCN guidelines for acute lymphoblastic leukemia (ALL): hypoploidy (< 44 chromosomes); t(v;11q23): mixed lineage leukemia (MLL) rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (>= 30,000 for B lineage or >= 50,000 for T lineage) \r\n*** For pediatrics t(9;22), intrachromosomal amplification of chromosome 21 (iAMP21)loss of 13q, and abnormal 17p \r\n** In CR2 or CR3 \r\n** With chemosensitive primary refractory disease \r\n* Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories
Acute lymphocytic leukemia\r\n* In complete first remission (CR1) in addition to one of the criteria outlined\r\n* Second or greater complete remission
Prior treatment (one of the following scenarios):\r\n* Primary refractory: for newly diagnosed AML, patients must have achieved two consecutive induction attempts without achieving complete remission\r\n* Relapsed/refractory: for patients initially in complete remission whose AML relapses > 6 months after preceding remission, one re-induction must be attempted to be eligible\r\n* Relapsed/untreated: for AML patients with early relapse, in whom the preceding remission is shorter than 6 months duration, no re-induction regimen is necessary to be eligible
Disease status must be complete remission by standard criteria for lymphoma and acute leukemia patients
Acute myelogenous leukemia (AML): high-risk AML including:\r\n* Antecedent hematological disease (e.g., myelodysplasia [MDS])\r\n* Treatment-related leukemia\r\n* Complete remission (first complete remission [CR1]) with poor-risk cytogenetics or molecular markers (e.g. fms-related tyrosine kinase 3 [Flt 3] mutation, 11q23, del 5, del 7, complex cytogenetics)\r\n* Second complete remission (CR2) or third complete remission (CR3) or induction failure or 1st relapse with either\r\n** =< 10% blasts in the marrow or \r\n** =< 5% blasts in the peripheral blood
Subjects must meet one of the disease classifications listed below:\r\n* Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity, peripheral blood counts showing absolute neutrophil count (ANC) > 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp)  \r\n** Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by at least one of the following: \r\n*** Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements \r\n*** White blood cell counts > 30,000/mcL\r\n*** Patients over 30 years of age\r\n*** Time to complete remission > 4 weeks\r\n*** Presence of extramedullary disease\r\n** Acute myelogenous leukemia in high risk CR1 as defined by at least one of the following: \r\n*** Greater than 1 cycle of induction therapy required to achieve remission \r\n*** Preceding myelodysplastic syndrome (MDS) \r\n*** Presence of Fms-like tyrosine kinase 3 (Flt3) abnormalities\r\n*** French-American-British classification (FAB) M6 or M7 leukemia or\r\n*** Adverse cytogenetics for overall survival such as:\r\n**** Those associated with MDS \r\n**** Complex karyotype (>= 3 abnormalities)\r\n**** Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)\r\n** Acute leukemias in 2nd or subsequent remission\r\n** Biphenotypic/undifferentiated leukemias in 1st or subsequent complete remission (CR)\r\n** High-risk MDS status-post cytotoxic chemotherapy\r\n** Myelofibrosis\r\n* Burkitt’s lymphoma: second or subsequent CR\r\n* Lymphoma\r\n** Chemotherapy-sensitive (complete or partial response) large cell, mantle cell or Hodgkin’s lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant or relapsed/progressed after autologous stem cell transplant\r\n** Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan) and are ineligible for an autologous transplant or relapsed/progressed after autologous stem cell transplant
Patients who have undergone an autologous HCT for the treatment of DLBCL and are in a complete remission (CR), partial remission (PR) or have stable disease (SD) at the day 28 post-transplant reassessment
Patients aged 18 to 55 years with high risk AML who have achieved their FIRST complete remission (CR) or complete remission with incomplete recovery (CRi) within 12 months of enrollment and are not immediately candidates for allogeneic stem cell transplant; patients above age 55 who are not eligible for other protocols may be considered for enrollment on a case by case basis after discussion with the principal investigator (PI)
Acute lymphocytic leukemia or acute myelogenous leukemia who are not in first remission or second remission i.e. after failing induction therapy, or in relapse or beyond second remission; (prior therapy with VP-16 and Cytoxan is allowed)
Patients in complete remission with no assessable disease
Patients with hematologic malignancies for whom autologous stem cell transplantation is deemed clinically appropriate:\r\n* Non-Hodgkin’s lymphoma, or Hodgkin’s lymphoma: either in a first complete remission (CR1) or refractory/relapsed with chemosensitive disease in a complete remission (CR) or partial remission (PR)\r\n* Multiple myeloma in first or second remission; patients with CR or PR will be eligible for this protocol
Disease Criteria: \r\n* ALL in complete remission (CR) at the time of transplant; remission is defined as “less than 5.0% bone marrow lymphoblasts by morphology,” as determined by a bone marrow aspirate obtained within 2 weeks of study registration\r\n* Philadelphia chromosome positive ALL is allowed\r\n* Lymphoid blastic crisis of chronic myelogenous leukemia (CML) will be included (provided that patients achieve CR)
Note: Patients who have received transplant during 1st remission are excluded since this would be considered a 2nd treatment
Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as: (i) greater than 1 cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT3 mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g. DNMT3A, TET2); (iv) French-American-British Classification (FAB) M6 or M7 classification; (v) adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (> 3 abnormalities); (vi) treatment-related AML, or b. second or greater remission; patients beyond second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction
PHASE II ONLY: More than one course of salvage chemotherapy for primary induction failure or AML relapsing after first complete remission (CR1)
Patients must have a histologically and cytological confirmed acute myeloid leukemia, high risk AML defined as:\r\n* Age > 60, or\r\n* Presence of complex cytogenetic abnormalities (with > 3 cytogenetic abnormalities), del (7q, -5, -7), t(9,22), 11q (23) or high risk mutations by fluorescence in situ hybridization (FISH) eg mixed lineage leukemia (MLL) , FMS-like tyrosine kinase 3 positive (FLT-3 +), or\r\n* Secondary AML, or\r\n* A white blood cell count of > 50 x 10^9/L\r\n* Failure to achieve complete remission (CR) with single standard induction
Cohort B: newly diagnosed AML, failed to achieve complete remission (CR) with single standard induction chemotherapy (chemo)
PHASE I: Diagnosis of a hematological malignancy listed below (excluding myelofibrosis) in remission or with stable minimal residual disease\r\n* Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse after any remission\r\n* Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse after any remission\r\n* Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System\r\n* Chronic myelogenous leukemia (CML) in accelerated or second chronic phase\r\n* Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse\r\n* Chronic lymphocytic leukemia (CLL), Rai stage 2-4, failing at least 2 prior regimens\r\n* Multiple myeloma (MM), stage 2-3\r\n* Myeloproliferative disorder or neoplasm
AML in 1st relapse or >= 2nd remission
Acute lymphoblastic leukemia (ALL/LL) in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL >= 2nd remission
Non-Hodgkin lymphoma with chemoresponsive disease in any of the following categories:\r\n* Intermediate or high grade lymphomas who have failed to achieve a first complete remission (CR) or have relapsed following a 1st remission who are not candidates for autologous transplants\r\n* Any non-Hodgkin lymphoma (NHL) in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant
Any patient, regardless of age or sex, with EBV-positive Hodgkin’s or non-Hodgkin’s lymphoma, (regardless of the histological subtype) or EBV (associated)-T/NK-lymphoproliferative disease or severe chronic active EBV (CAEBV); in second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse) OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter’s transformation of chronic lymphocytic leukemia (CLL) (Group A); OR in remission or with minimal residual disease status after autologous or syngeneic stem cell transplantation (SCT) (Group B)
Any patient, regardless of age or sex, with EBV-positive Hodgkin’s or non-Hodgkin’s lymphoma (regardless of histologic subtype), or EBV (associated)-T/NK-lymphoproliferative disease or severe chronic active EBV (CAEBV) and; in second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse) OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the lymphoma is a second malignancy e.g. a Richter’s transformation of CLL (Group A); patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant; OR in remission or with minimal residual disease status after autologous or syngeneic SCT (Group B)
Patients in first remission are eligible
AML in 1st relapse or >= 2nd remission
ALL/CLL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL >= 2nd remission
Non-Hodgkin’s lymphoma with chemoresponsive disease in any of the following categories: \r\n* Intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants\r\n* Any non-Hodgkin lymphoma (NHL) in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant
Standard risk patients will include eligible patients, as defined above, who are receiving transplants as treatment for MDS in RA/RCMD, RARS, AML in 1st or 2nd remission, ALL in 1st CR, NH in 1st remission, MM in 1st remission, very good partial response, or 1st partial response on the CML in the first chronic phase or 1st remission
Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by at least one of the following: \r\n* Adverse cytogenetics including but not limited to t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements\r\n* White blood cell counts > 30,000/mcL\r\n* Patients over 30 years of age\r\n* Time to complete remission > 4 weeks\r\n* Presence of extramedullary disease\r\n* Minimal residual disease\r\n* Other risk factors determined by the patient’s attending physician to be high risk features requiring transplantation
High-risk NB (as defined above) and in 1) first CR/VGPR at >= 6 months from initiation of immunotherapy using anti-GD2 antibody, or 2) second or subsequent remission; remission is defined as complete (CR) or very good partial (VGPR) remission, according to the International Neuroblastoma Response Criteria; urine catecholamine levels are no longer taken into consideration when staging; patients can be considered as in VGPR with 1 or 2 MIBG (+) sites that were previously-irradiated
Acute myelogenous leukemia (AML): \r\n* Complete first remission (CR1) at high risk for relapse such as: \r\n** Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder; \r\n** Therapy related AML; \r\n** White cell count at presentation > 100,000; \r\n** Presence of extramedullary leukemia at diagnosis; \r\n** Any unfavorable subtype by French-American-British (FAB) or World Health Organization (WHO) classification; \r\n** High-risk cytogenetics (e.g. those associated with MDS, abnormalities of 5, 7, 8, Philadelphia chromosome, complex karyotype) or high risk molecular abnormalities;\r\n** Requirement for 2 or more inductions to achieve CR1\r\n** Any patient with newly diagnosed AML with intermediate risk cytogenetics\r\n** Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician\r\n* Complete second remission (CR2)
Acute lymphoblastic leukemia (ALL): \r\n* Complete first remission (CR1) at high risk for relapse such as: \r\n** White cell count at presentation > 30,000 for B-cell lineage and >100,000 for T-cell lineage; \r\n** Presence of a high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality; \r\n** Failure to achieve complete remission after four weeks of induction therapy; \r\n** Any patient with newly diagnosed ALL >= 50 years-old;\r\n** Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician\r\n* Complete second remission (CR2)
Acute lymphocytic leukemia (ALL) at the following stages:\r\n* High risk first remission, defined as:\r\n** Philadelphia chromosome positive (Ph+) ALL; or\r\n** Mixed lineage leukemia (MLL) rearrangement with slow early response [defined as having M2 (5-25% blasts) or M3 (> 25% blasts on bone marrow examination on day 14 of induction therapy); or\r\n** Hypodiploidy (< 44 chromosomes or deoxyribonucleic acid [DNA] index < 0.81); or\r\n** End of induction M3 bone marrow; or\r\n** End of induction M2 marrow or MRD > 1% with M2-3 marrow or MRD > 1% at day 42\r\n** High-risk infant ALL defined as age < 6 months at diagnosis with MLL (11q23) translocation\r\n* High risk second remission, defined as:\r\n** Bone marrow relapse < 36 months from induction; or > 36 months (mths) if a matched sibling donor is available\r\n** T-lineage relapse at any time; or,\r\n** Very early isolated central nervous system (CNS) relapse (< 18 months from diagnosis); or\r\n** Slow reinduction (M2-3 at Day 28) after relapse at any time\r\n* Any third or subsequent CR
All children and adults with AML who have achieved a first or second bone marrow remission are eligible for this protocol; patients must undergo peripheral blood stem cell collection or marrow harvest while in remission and must not be expected to have better outcomes with allogeneic transplantation
Acute lymphocytic leukemia (ALL) at the following stages:\r\n* High risk first remission, as determined by treating physician as per current guidelines\r\n* Secondary remission, defined as:\r\n** Bone marrow relapse < 36 months from induction; or,\r\n** T-lineage relapse at any time; or,\r\n** Isolated CNS relapse or,\r\n** Slow reinduction (M2-3 at day 28) after relapse at any time\r\n* Any third of subsequent complete remission (CR)
Acute myelogenous leukemia (AML)\r\n* High risk first complete remission (CR1), as determined by treating physician as per current guidelines\r\n* Second or greater CR\r\n* First relapse with < 25% blasts in bone marrow\r\n* Patients with therapy-related AML whose prior malignancy has been in remission for at least 12 months
Chronic lymphocytic leukemia (must have all three): Rai Stage III/IV; progression after previous complete remission (CR) or partial remission (PR) including purine antagonist (i.e. fludarabine); recent chemotherapy responsiveness
A histologically or pathologically confirmed diagnosis of AML based on WHO classification which is previously untreated by systemic therapy or is in first relapse after achieving a complete remission to initial induction, consolidation and/or maintenance therapy or MDS with IPSS scores of intermediate -2 or higher risk risk which has been previously treated with hypomethylating agents
Very high risk pediatric patients with ALL; patients < 21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction; they are eligible once they achieved a complete remission
Very high risk pediatric patients with ALL: patients < 21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction; they are eligible once they achieve a complete remission
Patients with a history of any other cancer, unless in complete remission, and off all therapy for that disease for a minimum of 5 years
Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-related tyrosine kinase 3 [FLT3] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome, any disease beyond first remission
Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with t(9;22) or t(4;11), hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); double hit lymphomas in first remission or more advanced disease
History of lymphoma (Richter’s syndrome) unless in complete remission > 2 years without\r\nrelapse
In CR or complete remission with incomplete blood count recovery (CRi) after 1-2 induction chemotherapy documented by a bone marrow examination done within 2 weeks of starting cytarabine in this protocol
High-risk acute myeloid leukemia (AML) with predicted risk of relapse higher than 30%, which includes, but not limited to the following:\r\n* Patients in morphological remission (complete response 1 [CR1] or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers.\r\n* Patients with the following karyotypes in morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi): European LeukemiaNet (ELN)-Intermediate I, Adverse, ELN-Intermediate-II. (Examples include monosomal karyotype, complex karyotype, mutant p53, mutant RUNX1, mutant ASXL1, mutant FLT3-ITD, mutant DNMT3A, inversion 3, T(6:9), KIT mutated core binding factor AML)
Relapsed and/or refractory AML from any duration of complete remission (CR); any number of prior therapies allowed
NOTE: All patients achieving CR or complete remission with incomplete blood count recovery (CRi) will receive consolidation when fit
Relapsed after achieving remission with a prior therapy
Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:\r\n* Hodgkin’s lymphoma beyond first remission or first partial remission or induction failure with subsequent response to salvage therapy\r\n* Non-Hodgkin’s lymphoma beyond first remission or first partial remission or induction failure with subsequent response to salvage therapy\r\n* Chemotherapy responsive disease
Acute leukemia, primary refractory or beyond complete remission (CR)1, or minimal residual disease (MRD) positivity
Acute myelogenous leukemia— high risk in first complete remission (CR1) (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, or > 2 cycles to obtain complete remission [CR]); second or greater CR; must be in remission by morphology; patients in morphologic relapse/ persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (eg auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible for arms 2 or 3; note cytogenetic evidence of disease alone without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration versus (vs) early relapse is acceptable provided there are no associated cytogenetic markers consistent with relapse
Diagnoses to be included:\r\n* Acute Myelogenous Leukemia at the following stages:\r\n** First remission (cytogenetic intermediate or high risk)\r\n** Second or subsequent remission\r\n*** Complete remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment and < 5% blasts in the bone marrow\r\n* Chronic Myelogenous Leukemia at the following stages:\r\n** First or subsequent chronic phase:\r\n*** Patient refused tyrosine kinase therapy or is otherwise not suited for it\r\n*** Patient who has failed two lines of tyrosine kinase therapy (e.g., patient has not had a complete hematologic response and/or minor cytogenetic response by 3 months of second line therapy, major cytogenetic response by 12 months of second line treatment, or complete cytogenetic remission (CCyR) by 18 months of second line treatment)\r\n*** Patient who has lost complete hematologic response or major/complete cytogenetic response while on second line of therapy\r\n** Accelerated Phase – any one of the following symptoms:\r\n*** White blood cell (WBC) difficult to control (> 50 x 10^9/L despite therapy)\r\n*** Rapid doubling of WBC (< 5 days)\r\n*** 10% blasts in blood or marrow\r\n*** 20% blasts and/or promyelocytes in blood or marrow\r\n*** 20% basophils and/or eosinophils in blood\r\n*** Anemia or thrombocytopenia unresponsive to standard treatment\r\n*** Persistent thrombocytosis (> 1000 x10^9/L)\r\n*** Cytogenetic abnormalities in addition to Philadelphia positive (Ph+)\r\n*** Increasing splenomegaly\r\n*** Marrow fibrosis\r\n* Myelodysplastic syndromes at any of the following stages:\r\n** Refractory anemia\r\n** Refractory anemia with ringed sideroblasts\r\n** Refractory cytopenia with multilineage dysplasia\r\n** Refractory cytopenia with multilineage dysplasia and ringed sideroblasts\r\n** Refractory anemia with excess blasts-1 (5-10% blasts)\r\n** Refractory anemia with excess blasts-2 (10-20% blasts)\r\n** Myelodysplastic syndrome, unclassified\r\n** MDS associated with isolated del (5q) (only after failing lenalidomide)\r\n** Low risk MDS patients would be eligible only if transfusion-dependent and failing standard therapy (i.e. hypomethylating agents)\r\n** Chronic Myelomonocytic Leukemia\r\n* Primary Myelofibrosis\r\n** Intermediate-2 risk or high risk disease\r\n** Patients should have extinguished standard of care options prior to being considered for this trial\r\n* Chronic Lymphocytic Leukemia\r\n** Complete remission: the disease is completely absent and no relapse occurred prior to the preparative regimen; requires all of the following: \r\n** Nodular partial remission: complete response with persistent lymphoid nodules in bone marrow\r\n** Partial remission: reduction of more than 50% in the disease burden regardless of the number of lines of therapy received\r\n** Eligibility will be limited to those who have at least failed a fludarabine-based regimen\r\n* Mature B cell malignancies (including mantle cell lymphoma, follicular lymphoma, diffuse large B cell lymphoma, non-Hodgkin lymphoma not otherwise specified)\r\n** Patients should have extinguished standard of care options prior to being considered eligible for this trial\r\n** First complete remission (CR1) confirmed: complete disappearance of all known disease; the term “confirmed” is defined as a laboratory and/or pathological or radiographic determination\r\n** CR1 unconfirmed (CRU1): complete disappearance of all known disease with the exception of persistent scan abnormalities of unknown significance; the term “unconfirmed” is defined as scan abnormalities of unknown significance that are not biopsied or otherwise evaluated\r\n** Second complete remission positive (CR2+) confirmed: the recipient relapsed, then achieved complete absence of disease without radiographic evidence of disease\r\n** CR2+ unconfirmed: the recipient has achieved a second or subsequent complete response but has persistent radiographic abnormalities of unknown significance\r\n** Partial remission: reductions of >= 50% in greatest diameter of all sites of known disease and no new sites
Patients must have one of the following disease types:\r\n* Acute myeloid leukemia (AML) with any of the following:\r\n** In first complete remission (CR1) with high-risk features defined by any of the following:\r\n*** Presence of any of the cytogenetics abnormalities: -5/5q-, -7/7q-, t(9:22), t(6;9), inv(3), 9q, 11q23 abnormalities, or complex karyotype with 3 or more abnormalities per clone\r\n*** Need for 2 cycles of induction therapy to achieve CR1\r\n*** Preceding history of myelodysplasia or the prior administration of chemotherapy for a non-myeloid malignancy (i.e., secondary AML)\r\n** Patients in second or subsequent complete remission (CR2, CR3, etc.)\r\n** Primary refractory or relapsed AML with peripheral blood blasts < 2.0x10^9/l or with extramedullary disease (excluding active disease of the central nervous system)\r\n* Acute lymphoblastic leukemia (ALL) with any of the following:\r\n** In CR1 with high-risk features defined by any of the following cytogenetic abnormalities, including Ph+, t(4;11), 11q23 abnormalities, or t(1;9)\r\n** Patients in second or subsequent complete remission (CR2, CR3, etc.)\r\n** Primary refractory or relapsed ALL with peripheral blood blasts < 2.0x10^9/l or with extramedullary disease (excluding active disease of the central nervous system)\r\n* Myelodysplasia with any of the following features: \r\n** Refractory anemia with excess blasts with 11-20% blasts in the bone marrow (RAEB II)\r\n** Refractory anemia with excess blasts with 5-10% blasts (RAEB I) and poor risk cytogenetics (i.e., chromosome 7 abnormalities or complex karyotype with at least 3 abnormalities per clone)\r\n** Refractory cytopenia with multilineage dysplasia (RCMD) and poor risk cytogenetics (i.e., chromosome 7 abnormalities or complex karyotype with at least 3 abnormalities per clone)\r\n* Chronic myelogenous leukemia (CML) with one of the following criteria:\r\n** Accelerated phase, defined by any of the following:\r\n*** Blasts 10-19% of peripheral blood white cells or bone marrow cells\r\n*** Peripheral blood basophils at least 20%\r\n*** Persistent thrombocytopenia (< 100 x 10^9/l) unrelated to therapy, or persistent thrombocytosis (> 1000 x 10^9/l) unresponsive to therapy \r\n*** Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy\r\n*** Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase)\r\n*** Resistance to tyrosine kinase inhibitors (e.g., imatinib, dasatinib, nilotinib) defined as no complete cytogenetic response even if the above criteria are not met\r\n** First chronic phase provided a complete hematologic remission was not achieved by 3 months or a complete cytogenetic remission by 18 months and the patient had received in addition to imatinib 400 mg daily at least one of the following options: a) imatinib 600-800 mg daily, b) nilotinib, or c) dasatinib\r\n** Second or subsequent chronic phase provided a complete hematologic remission was not achieved by 3 months or a major cytogenetic remission (< 35 % Philadelphia chromosome + metaphases) by 6 months and the patient had received in addition to imatinib 400 mg daily at least one of the following options: a) imatinib 600-800 mg daily, b) nilotinib, or c) dasatinib\r\n* Patients with aggressive non-Hodgkin’s lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the following criteria:\r\n** Failure to achieve complete remission to primary induction therapy\r\n** Relapsed and refractory to at least one line of salvage systemic therapy
Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)
Hematologic malignancies diagnoses:\r\n* Acute lymphoblastic leukemia (ALL) with a history of bone marrow relapse in clinical remission (CR) #2 or greater, or in CR#1 if prior induction failure; or with an M1 marrow if unable to achieve CR\r\n* Philadelphia chromosome positive ALL patients who:\r\n** Have progressed through or relapsed following tyrosine kinase inhibitor (TKI) therapy or conventional myeloablative therapy OR\r\n** Are ineligible to receive tyrosine kinase inhibitor (TKI) therapy AND myeloablative hematopoietic stem cell transplant (HSCT)\r\n* Acute myelogenous leukemia (AML) with a history of bone marrow relapse in remission CR #2 or greater; or with an M1 marrow if unable to achieve CR; or in CR#1 if prior induction failure; or any of the following high-risk categories:\r\n** FMS-like tyrosine kinase 3/internal tandem duplication positive (FLT3/ITD+) with high allelic ratio > 0.4 (HR FLT3/ITD+) regardless of low risk features\r\n** Presence of monosomy 7, monosomy 5, or deletion (del)5q, without inversion (inv)(16)/t(16;16) or t(8;21) cytogenetics or nucleophosmin (NPM) or CCAAT enhancer-binding protein (CEBP) alpha mutations\r\n** AML without inv(16)/t(16;16), t(8;21), NPM, CEPB alpha mutations, monosomy 7, monosomy 5, del5q, or HR FLT3/ITD+, but with evidence of residual AML (>= 0.1%) at end of induction I\r\n* Hodgkin’s and non-Hodgkin’s lymphoma with refractory disease or relapse after at least one salvage regimen, or after autologous stem cell transplant\r\n* Juvenile myelomonocytic leukemia (JMML) with < 10% blasts in marrow and blood, who are not eligible for effective standard therapies\r\n* Chronic myelogenous leukemia (CML) with history of blast crisis (ALL/AML) or progressive disease failing tyrosine-kinase inhibitor (TKI)
Mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)
Lymphoblastic lymphoma \r\n* All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)\r\n* Patients with any high-risk features will be eligible in first complete remission \r\n* High risk features include: \r\n** Stage IV\r\n** Lactate dehydrogenase (LDH) > 2 x normal\r\n** >= 2 extranodal sites
Burkitt’s/Burkitt’s like\r\n* All patients except localized lymphoma will be eligible anytime after initial therapy (after achievement of first complete remission), or in partial remission if they fail to achieve CR\r\n* Patients with localized (stage I or Ziegler stage A) will be eligible only if they fail to achieve CR1 or after relapse
Chronic lymphocytic leukemia\r\n* Relapse post-fludarabine\r\n* Non-complete remission (CR) after salvage regimen
Subject did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A subject eligible for standard therapy must receive at least one cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A subject not eligible for standard therapy must have received at least one complete block of induction therapy seen as the optimum choice of therapy to induce remission for this subject.
First Complete remission (CR)/ Complete remission with incomplete blood count recovery (CRi) with induction therapy + consolidation therapy within 4 months (+/- 7 days of achieving CR or CRi)
Participants with hematologic malignancies or hematologic disorders for whom allogeneic stem cell transplantation is deemed clinically appropriate; eligible diseases and stages include:\r\n* Non-Hodgkin's lymphoma, or Hodgkin's lymphoma in second (2nd) or subsequent complete remission or in partial remission with documented chemosensitivity to the most recent chemotherapy regimen; prior autologous transplantation is required, unless deemed medically inappropriate by the treating physician\r\n* Multiple myeloma: relapsed but with chemosensitive disease; bone marrow plasma cells may not exceed 20% of the total cellularity\r\n* Chronic lymphocytic leukemia: any Rai stage III or IV, lymphocyte doubling time of 6 months, or stage I-II with progression after >= 2 chemotherapy regimens, in partial remission with documented chemosensitivity to the most recent chemotherapy regimen\r\n* Acute myelogenous or acute lymphoblastic leukemia in second or subsequent complete remission or in first remission with adverse cytogenetic/molecular features or a documented antecedent hematologic disorder\r\n* Myelodysplastic disorder\r\n* Myeloproliferative disorder including myelofibrosis, chronic myelogenous leukemia resistant to tyrosine kinase inhibitors\r\n* Aplastic anemia with no response to immunosuppressive therapy
Enrollment on protocol for collection of PBMC/T cells may occur for the following patients with CD19+ B-ALL\r\n* Patients whose disease meets one of the following 3 criteria:\r\n** Very high-risk (VHR)\r\n** Patients in first (1st) or subsequent marrow relapse (isolated or combined), at the time of relapse, during retrieval therapy, or after achievement of complete remission (CR)\r\n** Refractory disease\r\n** Definitions of VHR B-ALL include the following:\r\n*** National Cancer Institute (NCI) high risk (HR)-acute lymphoblastic leukemia (ALL) and age >= 13 years at diagnosis\r\n*** Overt central nervous system disease (CNS-3) leukemia at diagnosis\r\n*** Day 29/end of induction bone marrow (BM) minimal residual disease (MRD) > 0.01%\r\n*** Induction failure (M3 BM at day 29/end of induction)\r\n*** Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81)\r\n*** t(9;22) ALL (Philadelphia chromosome/Ph+ ALL) or Ph-like ALL\r\n*** t(17;19) ALL\r\n*** MLL gene rearrangement\r\n*** IKAROS family zinc finger 1 (Ikaros) (IKZF1) deletions\r\n*** Intrachromosomal amplification of chromosome 21 (iAMP21)\r\n* Please note patients that only meet the criteria for collection/storage of PBMCs will need to re-consented prior to infusion of genetically modified T-cells
have prior or concurrent malignancies, inclusive of hematologic, primary brain tumor, sarcoma, and other solid tumors, unless in complete remission with no therapy for a minimum of 5 years
Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)
Patients with multiple myeloma in complete remission (CR), partial remission (PR), or very good partial remission (VGPR), or symptomatic stable disease (no evidence of progression) including patients with light chain MM detected in the serum by free light chain assay
Participants must have chemosensitive disease prior to ASCT, defined as achieving at least a partial remission (as determined with PET imaging) to salvage treatment using International Harmonization Project (IHP) criteria; participants with cHL or DLBCL (arms A and B) transplanted in first (1st) remission after only one line of treatment are not eligible; participants with PTCL (arm C) transplanted beyond 1st remission are also not eligible
Patients meeting the Durie and Salmon criteria for initial diagnosis of multiple myeloma, requiring therapy and meeting one of the following:\r\n* After initial therapy in either first complete or partial remission or no objective response\r\n* After achieving initial response and later disease progression, patient will be eligible after subsequent therapy upon achievement of either complete or partial response
Patient is currently in complete cytogenetic remission (CCyR)
Patients will have relapsed at least once and returned to complete clinical remission after additional chemotherapy; interval surgery is permitted
This treatment is for patients with high risk hematologic malignancies; high risk is defined as:\r\n* Any patient with a hematologic malignancy with residual disease after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely\r\n* Patients without morphologic evidence of disease but with high risk features which would predict for relapse despite remission at HSCT such as adverse cytogenetics, 3rd or greater complete remission (CR), or failure to recover peripheral blood counts to normal ranges; while these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive
Acute myelogenous leukemia (AML) in complete morphological remission at study screening (Complete Remission with Incomplete Platelet Recovery (CRp) acceptable).
Acute lymphoblastic leukemia (ALL) in complete morphological remission at study screening (Complete Remission with Incomplete Platelet Recovery (CRp) acceptable).
Patients must have had a previous auto-SCT performed as part of a consolidation of an initial remission and had a remission, defined as a partial response or greater that lasted at least 12 months either on or off maintenance therapy without evidence of progression as defined by IMWG criteria
Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia\r\n* High risk first complete remission (CR1) (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements, hypodiploid); or high risk (HR) as defined by referring institution treatment protocol greater than 1 cycle to obtain CR; second complete remission (CR2) or greater\r\n* All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age\r\n* Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment
Patients must have partial remission (PR) to salvage chemotherapy
Patients not in remission must have CD45-expressing leukemic blasts; patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up >= 95% of nucleated cells in the marrow)
Underlying cancer in remission
Biphenotypic leukemia that at the time of allogeneic transplantation was in induction failure, relapsed disease, first, second or greater remission
Patients must be in complete remission post transplant
Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission, or first complete remission (CR1) considered at risk for relapse
Acute lymphocytic leukemia with induction failure, first complete remission with high risk cytogenetics (e.g. Philadelphia positive chromosome, t[4:11]; remission requiring more than 2 chemotherapy to achieve remission, or any stage beyond CR1
Patients not in remission must have cluster of differentiation (CD)45-expressing leukemic blasts; patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up >= 95% of nucleated cells in the marrow)
Burkitt or acute lymphoblastic lymphomas\r\n* High-risk disease in remission\r\n* Primary refractory disease\r\n* Recurrent disease\r\n* Relapse/progression after autologous HSCT
Acute myelogenous leukemia\r\n* In first complete remission with high-risk cytogenetics\r\n* Primary induction failure\r\n* In second or greater complete remission\r\n* Secondary AML\r\n* In first complete remission with hyperleukocytosis at diagnosis
Acute lymphocytic leukemia\r\n* First complete remission, with high-risk cytogenetics\r\n* Primary induction failure\r\n* Second or greater complete remission
Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-related tyrosine kinase 3 [flt3] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell histiocytosis, any disease beyond first remission; or
Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma; or
Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); double hit lymphomas in first remission or more advanced disease; or
Relapse after achieving initial remission or failure to achieve initial remission
Acute myeloid leukemia (AML) in >= first (1st) remission - excluding those in 1st remission with ‘good risk’ cytogenetic features (i.e. t(8;21), t(15;17), inv 16)
Acute lymphoblastic leukemia (ALL)/lymphocytic leukemia (LL) in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL > second (2nd) remission
The patient has relapsed or refractory B or T cell acute lymphoblastic leukemia that has progressed following at least one prior therapy; Philadelphia chromosome-positive (Ph+) patients are eligible; relapsed ALL is defined in patients as the reappearance of leukemia cells in the peripheral blood or bone marrow or appearance of extramedullary disease after a complete remission; refractory ALL is defined in patients as failure to achieve a complete remission after induction therapy; complete remission is defined by < 5% leukemia cells in the bone marrow with recovery of peripheral blood counts; relapsed disease can be documented by bone marrow biopsy (> 5% cells in the bone marrow) or by flow cytometry in the peripheral blood or biopsy of extramedullary disease
Relapse after going into remission from re-induction for the first or subsequent relapse (ie: 2nd , 3rd, 4th…relapse), OR
Patients to be enrolled in the dose-escalation portion of this study must have T-cell ALL or T-cell lymphoblastic lymphoma (LL) in first relapse or must have failed primary induction chemotherapy (ie, never attained a complete remission following an initial course of standard therapy for T-ALL or T-LL). Patients to be enrolled in the cohort expansion portion of this study (ie, those treated at the recommended phase 2 dose) must have T-cell ALL in first relapse or must have failed primary induction chemotherapy (ie, never attained a complete remission following an initial course of standard therapy for T-ALL). T-LL patients are not eligible for the cohort expansion phase.
Patient should have a responsive skin disease including complete remission (CR) and partial remission (PR) (close to CR; 75%-99% clearance of skin disease from baseline without new tumors (T3) in patients with T1, T2 or T4 only skin disease) and should not have visceral organ or lymph node involvement prior to transplantation
Bone marrow in morphologic remission (any remission number) defined as < 5% blasts (M1 classification) performed in local institution lab
One of the following:\r\n* Acute leukemia past first remission, in first or subsequent relapse, in second or greater remission; patients in first remission should have with intermediate or high cytogenetic risk factors or fms-related tyrosine kinase 3 (flt3) mutation; patients with relapsed disease; patients with primary induction failure or relapse are eligible if they have < 10% bone marrow blasts, and no circulating blasts\r\n* Myelodysplastic syndrome with intermediate or high risk International Prognostic Scoring System (IPSS) score, or treatment related myelodysplastic syndrome (MDS)\r\n* Chronic myeloid leukemia (CML) resistant to tyrosine kinase treatment in a first or subsequent chronic phase or after transformation to accelerated phase or blast crisis\r\n* Chronic lymphocytic leukemia (CLL), lymphoma or Hodgkin’s disease which has failed to achieve remission or recurred following initial chemotherapy; patients must have at least a PR to salvage therapy, or low bulk untreated relapse (< 2 cm largest mass)\r\n* Multiple myeloma which has relapsed or progressed and has achieved a partial response to salvage chemotherapy
A confirmed baseline diagnosis of AML by the revised guidelines of the International Working Group for AML including newly diagnosed, relapsed or refractory disease\r\n*Newly diagnosed: \r\n** Age 70 years and older \r\n** 60-69 years old and unfit for conventional chemotherapy\r\n* Relapsed disease: \r\n** Age 60 years and older any time following the first relapse, if the patient is not considered candidate for or is not interested in salvage chemotherapy\r\n** Age 18-59 years who have relapsed less than 6 months following achievement of a complete remission (defined as duration of remission from the time of documentation of complete morphologic remission to the time of documentation of relapse)\r\n* Refractory disease: \r\n** Age 18-59 years who have failed at least two lines of conventional chemotherapy (one induction and one salvage therapy); examples include: \r\n*** Patient achieves a complete remission and receives (or does not receive) consolidation therapy, but relapses later; this patient will be eligible only if s/he fails at least one salvage therapy following relapse\r\n*** Patient demonstrates residual leukemia on post-induction day 14 bone marrow and receives salvage therapy; this patient will be eligible only if s/he fails the salvage therapy\r\n*** Patient demonstrates reasonable response on post-induction day 14 bone marrow (or the bone marrow is not performed), but the follow-up bone marrow shows residual disease; this patient will be eligible only if s/he fails at least one salvage therapy\r\n** Age 60 and older who have failed at least one line of conventional chemotherapy, or treatment with hypomethylating agent (in the setting of poor-risk/complex karyotype) and is not considered candidate for or is not interested in salvage chemotherapy; FltITD +ve disease is not considered responsive to hypomethylating agent\r\n* Patients age 18 years and older with relapse in the form of AML after stem cell transplant will be eligible, even if they were transplanted for myelodysplastic syndromes (MDS) or myeloproliferative neoplasm (MPN)
Patients with a history of any other cancer, unless in complete remission, and off all therapy for that disease for a minimum of 5 years
Acute lymphoblastic leukemia \r\n* >= second complete remission (CR2) (adults >= 18 years and =< 55 years) \r\n* CR2 in pediatrics (defined as < 18 years) and < 12 months duration of first remission\r\n* >= third complete remission (CR3) or not in remission (pediatric patients < 18 years)\r\n* T cell leukemia >= CR2\r\n* Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, fluorescence in situ hybridization (FISH) or cytogenetics
Acute myeloid leukemia\r\n* Not in remission (pediatric patients < 18 years)\r\n* Not in remission (10-30% blasts in the bone marrow for adult patients >= 18 years and =< 55 years)\r\n* Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics
Individuals who have undergone transplant for hematologic malignancy are required to be in complete remission.
Patients must have one of the following hematologic malignancies: \r\n* Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-like tyrosine kinase [flt]3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhans cell histiocytosis, any disease beyond first remission; or\r\n* Myelodysplastic syndrome (MDS): primary or therapy related; or\r\n* Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma; or \r\n* Non-Hodgkin's lymphoma (NHL): in primary induction failure, second or third complete remission, refractory disease, or relapse (including relapse post autologous hematopoietic stem cell transplant); double hit lymphomas in first remission or more advanced disease; or \r\n* Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following standard therapy; or,\r\n* Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase; or,\r\n* Hodgkin's disease (HD): induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant)
Individuals with PMF, post-PV MF, or post-ET MF who are receiving ruxolitinib and meet 2013 Revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria with progressive and relapsed disease, with modifications for progressive disease complete remission (CR), partial remission (PR), or clinical improvement (CI)
Relapsed after achieving remission with a prior therapy
Prior or concurrent invasive malignant disease, unless in complete remission for more than three years.
Patients may be registered for consolidation provided that they were eligible for the initial induction/re-induction registration and satisfy the following additional criteria:\r\n* Patients must have achieved morphologic remission (complete remission [CR] or complete remission with incomplete blood count recover [CRi]) after completion of induction or re-induction therapy; patient must remain in remission until beginning consolidation and this must be documented by bone marrow and peripheral blood examination within 28 days prior to registration to Step 2\r\n* All non-hematologic treatment related toxicities that are deemed clinically significant by the treating physician must have resolved to =< grade 2\r\n* Patients must not have received allogeneic stem cell transplant
Inclusion Criteria:\n\n        Donor:\n\n          -  Donor eligibility will be determined according to applicable federal, state and local\n             regulations and institutional standards\n\n          -  18-65 years of age\n\n          -  6/6 HLA-matched sibling\n\n          -  Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor\n\n          -  Serum creatinine <2.0mg/dl\n\n        Recipient:\n\n          -  18 to 65 years of age\n\n          -  6/6 HLA antigen matched sibling willing to donate PBSC for transplant\n\n          -  Fulfill individual Transplant Center Criteria for transplant\n\n          -  One of the following diagnoses:\n\n               -  Acute myelogenous leukemia (AML) in 1st remission or beyond with <5% marrow\n                  blasts and no circulating blasts. Marrow must be done within 30 days of the start\n                  of transplant conditioning regimen in alignment with other pre-transplant\n                  assessments.\n\n               -  Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with <5% marrow\n                  blasts and no circulating blasts\n\n               -  Myelodysplastic syndrome, either intermediate-1,2, or high risk by International\n                  Prognostic Scoring System or transfusion dependent\n\n               -  Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase\n                  inhibitor based therapy\n\n               -  Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete\n                  remission, partial remission, or in relapse (but with at least stable disease\n                  after most recent therapy)\n\n               -  Chronic lymphocytic leukemia (CLL), relapsing after at least one prior regimen,\n                  or in remission with 17p deletion\n\n          -  Serum creatinine must be <2.0mg/dl\n\n          -  Total bilirubin and AST <3x normal\n\n          -  Infectious disease marker (IDM) monitoring will be performed per institutional\n             standards\n\n          -  Karnofsky performance status of 70% or greater.\n\n          -  Patients who have undergone a prior autologous transplantation are eligible for a\n             reduced intensity transplant only\n\n        Exclusion Criteria:\n\n        Donor:\n\n          -  Donor unwilling or unable to give informed consent, or unable to comply with the\n             protocol including required follow-up and testing\n\n          -  Donor already enrolled on another investigational agent study\n\n          -  Pregnant or breast feeding females, or females not willing or able to use adequate\n             contraception if sexually active\n\n        Recipient:\n\n          -  Patient unwilling or unable to give informed consent, or unable to comply with the\n             protocol including required follow-up and testing\n\n          -  Patients with active, uncontrolled infection at the time of the transplant preparative\n             regimen\n\n          -  Pregnant or breast feeding females, or females not willing or able to use adequate\n             contraception if sexually active\n\n          -  Patients with a history of previous CNS tumor involvement showing active symptoms or\n             signs along with documented disease on lumbar puncture and MRI of the brain within 30\n             days of start of conditioning\n\n          -  A condition, which, in the opinion of the clinical investigator, would interfere with\n             the evaluation of primary and secondary endpoints.
Acute myelogenous leukemia (AML) in first remission that required more than 1 cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT3 mutation, deletion/monosomy of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities; also patients in second or greater remission
Patients will be considered eligible for the study if after transplant they achieved hematologic (< 5% blasts) and cytogenetic remission
Underlying primary disease, for which the subject underwent transplant, is in morphologic remission
No plans for additional post-remission chemotherapy.
Relapsed, refractory, or progressive acute leukemia in second or subsequent remission, with remission defined as < 5% bone marrow blasts morphologically
Partial Remission (PR)
Morphologic complete remission with incomplete blood count recovery (CRi)
Acute lymphocytic leukemia (ALL) in first complete remission (CR1) with high-risk features including adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) gene rearrangements; ALL in second or greater remission or ALL with relapsed disease, peripheral blood blasts < 1000/microliter, ALL patients must show response to most recent received chemotherapy
AML in second or greater remission, primary induction failure and patients with relapsed disease, peripheral blood blasts < 1000/microliter; patients > 55 years and =< 75 years need to be in morphologic remission at transplant (< 5% blasts)
The patient is in morphologic leukemia-free state or in morphologic complete remission with incomplete blood count recovery (CRi).
Patients with multiple myeloma who have not achieved a complete remission (CR) following at least 4 cycles of induction therapy
Patients who are in complete remission or have a stable disease
Be in a complete remission.
Patients must meet one of the following:\r\n* Acute myeloid leukemia (AML) in first (1st) remission - for patients whose AML does not have \good risk\ cytogenetic features (i.e. t[8;21], t[15;17], inv 16 without v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog [c-kit] mutations)\r\n* Acute leukemias of ambiguous lineage in >= 1st remission\r\n* Secondary AML in remission\r\n* AML in >= second (2nd) remission\r\n* Acute lymphoblastic leukemia (ALL) in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL >= 2nd remission\r\n* Chronic myelogenous leukemia (CML) failing to respond or not tolerating imatinib, dasatinib or nilotinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in complete remission (CR) after accelerated phase or blast crisis\r\n* Non-Hodgkin lymphoma (NHL) with chemo responsive disease in any of the following categories:\r\n** Intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants\r\n** Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant\r\n* Myelodysplastic syndrome (MDS): refractory anemia (RA)/refractory cytopenia with multilineage dysplasia (RCMD) with high risk cytogenetic features or transfusion dependence, refractory anemia with excess blasts (RAEB)-1 and RAEB-2\r\n* Chronic myelomonocytic leukemia (CMML): CMML-1 and CMML-2
Must have a high risk hematologic malignancy as defined below; if the patient does not meet defined eligibility requirements as stipulated below, the principal investigator (PI) must be contacted to determine eligibility:\r\n* Acute myeloid leukemia (AML)\r\n** Patients with AML in the first complete remission (CR) with intermediate or high risk disease\r\n** Patients with AML in first CR with high-risk disease as defined by one of the following abnormalities; CR is defined as an M1 marrow (< 5% blasts by morphology), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L; cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment; complete remissions without platelet recovery (CRp) will be considered complete remissions
Indicators of High-risk Disease are as follows:\r\n*** Fms-related tyrosine kinase 3 (Flt3)/internal tandem duplication (ITD)+ (If quantitative testing was performed, the allelic ratio must be > 0.4)\r\n*** Residual marrow disease (>= 0.1%) detected by multidimensional flow cytometry after completing at least one cycle of induction chemotherapy\r\n*** Secondary AML; if the AML is secondary to treatment for another malignancy, the first malignancy must be in a complete remission\r\n*** High-risk cytogenetic abnormalities: Different high-risk cytogenetic criteria have been defined for adult and pediatric AML; we will, therefore, use two sets of cytogenetic criteria, one based on Children’s Oncology Group (COG) criteria for pediatric patients and one based on Southwestern Oncology Group (SWOG)/Eastern Oncology Group (ECOG) or Medical Research Council (MRC) criteria for adult patients; examples of high-risk cytogenetics: adult patients (>= 21 years): -5/deletion (del) (5q), -7/del (7q), inversion (inv)3q, del (9q), abnormality (abn)11q, abn 20q, abn21q, abn17P, translocation (t)(6;9), t(9;22), complex karyotypes (>= 3 unrelated abnormalities); pediatric patients (< 21 years): -5/del(5q), -7\r\n*** Other abnormalities associated with a higher risk for AML relapse; there are an increasing number of abnormalities being identified that have been associated with an intermediate or high risk of relapse, but have yet to be incorporated into cooperative group risk classification systems; patients with AML characterized by these abnormalities will be considered; the PI will need to approve such cases for enrollment\r\n** Patients with a partial first remission (PR, defined as an M2 marrow (5-19% blasts by morphology), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L; cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment\r\n** Patients in 2nd or greater complete or partial remission\r\n* Myelodysplastic syndrome\r\n** Adult patients (>= 21 years) with secondary disease or de novo disease that meets criteria for intermediate, high or very high-risk disease based on the Revised International Prognostic Scoring System; Intermediate risk (3.1-4.5 points), high risk (4.6-6 points), very high risk (> 6 points) \r\n** Pediatric patients with myelodysplastic syndrome (MDS), regardless of subtype, will be eligible\r\n* Acute lymphoblastic leukemia (ALL):\r\n** Given the poor prognosis of adults (>= 21 years) with ALL, adults in 1st or greater complete remission will be eligible; CR is defined as an M1 marrow (< 5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L; cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment; complete remissions without platelet recovery (CRp) will be considered remissions\r\n** Given the generally good prognosis of children (< 21 years) with ALL, they will have to meet one of the criteria listed below; additionally, children who are enrolled on a COG ALL trial for newly diagnosed or relapsed disease will have to meet the criteria for bone marrow transplant (BMT) outlined in that trial; CR is defined as an M1 marrow (< 5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count (ANC) >= 1.0 x 109/L; cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment; complete remissions without platelet recovery (CRp) will be considered remissions\r\n*** In 1st complete remission with a very high risk for relapse:\r\n**** Hyplodiploidy (< 44 chromosomes, as evidenced by the results of routine analysis of G-banded chromosomes, deoxyribonucleic acid (DNA) index (< 0.81), or other appropriate methodology)\r\n**** > 1% residual marrow blasts by flow cytometry at the end of induction\r\n**** > 0.01% residual marrow blasts by flow cytometry at the end of consolidation\r\n**** Early T-Cell Precursor (ETP) phenotype\r\n*** In 2nd complete remission with B-lineage disease after a marrow relapse occurring less than 36 months from diagnosis\r\n*** In 2nd complete remission with T-lineage disease or Philadelphia chromosome positive (Ph+) disease after a marrow relapse occurring at any time\r\n*** In a 2nd complete remission with T-lineage disease after an extra-medullary relapse occurring less than 18 months from diagnosis\r\n*** In 3rd or greater complete remission after a marrow or extramedullary relapse\r\n*** Other indications for transplant in pediatric patients with ALL must be approved by the study PI with a note to file reflecting study team discussion
Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following:\r\n* Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other mixed lineage leukemia (MLL) rearrangements\r\n* White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis\r\n* Recipient age older than 30 years at diagnosis\r\n* Time to CR greater than 4 weeks
All patients must be in complete remission (CR):
Acute myeloid leukemia (AML) with any of the following:\r\n* In first remission (CR1) with intermediate risk or high-risk cytogenetic and/or molecular features\r\n* Patients in second or subsequent complete remission (CR2, CR3, etc.)\r\n* Primary refractory or relapsed AML with no more than any one of the following adverse additional features according to modified Center for International Blood and Marrow Transplant Research (CIBMTR) criteria\r\n** Duration of first CR < 6 months\r\n** Poor risk cytogenetics or molecular features (FLT-3 internal tandem duplication [ITD]; complex karyotype with >= 3 clonal abnormalities, 5q-/-5, 7q-/-7, 11q23 abnormalities, inv(3), monosomal karyotype)\r\n** Circulating peripheral blood blasts at time of enrollment\r\n** Karnofsky performance status < 90%
Considered at high risk for relapse as defined by:\r\n* The presence of >= 1 of the following: failure to achieve complete response (CR) post initial treatment; relapsed disease with an initial remission duration of < 12 months; or extranodal involvement at the start of pre-transplant salvage therapy
Mantle-cell NHL - may be treated in first complete remission (CR); (diagnostic lumbar puncture [LP] required pre-transplant)
Acute myeloid leukemia (AML) in first cytomorphological remission (< 5% blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission
Acute lymphoblastic leukemia (ALL) second or greater complete remission (CR); first complete remission (CR1) unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics such as t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* 30 years of age or older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease\r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Acute myeloid leukemia (AML) in first remission with high-risk features or in second or higher remission
Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission
Disease Status: Neuroblastoma that is in remission
Diagnosis of acute leukemia (AML/ALL) or advanced MDS (intermediate-2 [INT-2] or high risk) in complete remission (complete remission [CR]/composite complete remission [CRc]/complete remission with incomplete hematologic recovery [CRi]) documented by bone marrow biopsy done within 30 days prior to the initiation of conditioning regimen
Disease Status: Neuroblastoma that is in remission
Failure to achieve any objective response (CR - complete remission, PR - partial remissino, mCR - marrow complete remission, or HI - hematologic improvement), but no evidence of disease progression within the 8 weeks leading to the subject's first dose of IP (INVESTIGATIONAL PRODUCT) in this study (Cycle 1, Day 1)
Any patient, regardless of age or sex, with EBV-positive Hodgkin’s or non-Hodgkin’s Lymphoma, or lymphoepithelioma/leiomyosarcoma regardless of the histological subtype or EBV (associated)-T/NK-lymphoproliferative disease or severe chronic EBV \r\n* In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse) OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of chronic lymphocytic leukemia (CLL) (Group A) OR\r\n* In remission or with minimal residual disease status after autologous or syngeneic stem cell transplantation (SCT) (Group B) OR\r\n* In remission or with detectable disease after allogeneic SCT (Group C)
Participants must have pathologically confirmed acute myeloid leukemia (AML) in first complete remission (CR1) as defined by:\r\n* Bone marrow biopsy with < 5% blasts\r\n* No clusters or collections of blast cells\r\n* No extramedullary leukemia\r\n* Absolute neutrophil count >= 1000/uL (achieved post-induction at some point)\r\n* Please note that full platelet recovery is not necessary, and thus, patients achieving pathological complete remission (CRp) are eligible
Diagnosis of pre-B cell or T cell ALL and in continuous first remission; at least 3 months into maintenance up until the first year off therapy
Previously diagnosed of ALL and currently in remission
Patients who have achieved complete remission of intestinal metaplasia (CR-IM)
In remission (complete remission [CR], partial remission [PR], or stable disease based on clinical, not necessarily radiologic, assessment) and currently being observed and with no current cytotoxic chemotherapy planned; patients may be on rituximab maintenance
Must have achieved an objective response (CR/PR) or stable disease (SD) upon completion of scheduled treatment
Patients must have achieved a CR or CRi
Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging BM aspirate and biopsy
Patients must be registered to Step 2 within 28 days after count recovery; (Note: there is no maximum allotted time period for count recovery, providing patient remains in CR or CRi)
Patients must have achieved a response to induction chemotherapy (either CR or PR by Cheson 2007 criteria) and be without known progression
leukemia in 1st relapse with initial CR duration < 6 months,
Calculated Cr Cl >= 30 ml/min; eligible for reduced dose methotrexate
The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR)
Achieved at least a partial response (PR) to therapy
Acute lymphoblastic leukemia (B- or T-acute lymphoblastic leukemia [ALL])\r\n* Complete response (CR)1-ultra high risk features\r\n** Unfavorable cytogenetics\r\n** Hypodiploidy\r\n** Induction failure\r\n** Minimal residual disease (MRD) positive after consolidation\r\n* CR2\r\n** Any of the high risk features listed in CR1\r\n** B-ALL: any relapse considered eligible for transplant \r\n** T-ALL\r\n* CR 3-any
Participant has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as < 5% blasts in the BM with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
Participants with CR with incomplete count recovery (CRp or CRi) are allowed. Incomplete platelet recovery (CRp) is defined as CR with platelet count < 100 x 109/L. Incomplete blood count recovery (CRi) is defined as CR with residual neutropenia < 1 x 109/L with or without complete platelet recovery. Red blood cell count (RBC) and platelet transfusion independence is not required.
The maximum time allowed from establishment of CR1 to registration is 12 months.
Participant has confirmed ongoing morphologically documented AML in CR1. For the purposes of randomization, CR1 will be defined as < 5% blasts with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
Patients must have received pre-study nivolumab for up to 12 months and have 2 consecutive tumor assessments confirming Complete response (CR), Partial response (PR), or Stable disease (SD)
Documented major response [partial response (PR), very good partial response (VGPR), complete response (CR)] according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.
Patients must have received at least one prior therapy for CLL or NHL, need additional treatment (or have need for cytoreduction as mentioned above), and meet criteria for relapsed or refractory disease; they may not be a candidate for curative therapy; relapsed disease is defined as a patient who previously achieved a complete remission (CR) or a partial remission (PR), but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic or anti-lymphoma therapy, or any response less than a CR or PR
Patients with HD with 4th or greater CR, PR, and/or SD are ineligible.
Creatinine (Cr) > 1.5 mg/dL or Cr clearance < 60 mL/m^2
Patients with B-lineage ALL in CR2 and beyond with molecular failure at any time point after 2 months of salvage therapy are allowed
On treatment with ruxolitinib for at least 3 months and have been on a stable dose for at least 8 weeks and have not achieved a complete response (CR) by International Working Group (IWG) criteria
Patients must have received treatment on PBTC-029 or PBTC-029B for a minimum of 12 courses with at least stable disease, or had a sustained response (partial response [PR]/ complete response [CR]) but remained on treatment < 12 courses
Absence of a documented partial response (PR) or complete response (CR) according to RECIST 1.1 or CA 125 response by Gynecologic Cancer Intergroup (GCIG) criteria to neoadjuvant chemotherapy
Disease response noted (i.e. CR, non-CR, or not applicable): assessed as per disease specific criteria
Diagnosis of one of the following: a): Patients >= 60 years of age with previously untreated Ph-positive ALL [either t(9;22) and/or BCR-ABL positive] (includes patients initiated on first course of therapy before cytogenetics known): This patient could have received one or two courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs) and still eligible; b) If they achieved CR, they are assessable only for event-free and overall survival; or c) If they failed to achieve CR, they are assessable for CR, event-free, and overall survival; d) Patients >= 18 years of age with relapsed/refractory Ph-positive ALL.
Previous tumor response to PD-1 or PD-L1 inhibiting therapy\r\n* Note: Tumor response is defined as complete response (CR), partial response (PR), or stable disease (SD) that is durable for at least 16 weeks
Patients with complete response (CR)/very good partial response (VGPR) disease
Patients >= 60 years of age with previously treated Ph-positive ALL, after 1-2 courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs). If they achieved CR, they are assessable only for event-free and overall survival, or If they failed to achieve CR, they are assessable for CR, event-free, and overall survival.
For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
Chemo-sensitive (defined by complete response [CR] or partial response [PR] to most recent chemo regimen) based on pre-transplant positron emission tomography (PET) within 6 weeks of autologous transplant
Achieved either partial or CR to the bendamustine regimen of at least 12 months in duration before relapse/progression.
Patients must be in first CR/VGPR
Patients must have: a. Relapsed and/or refractory non-APL AML that has failed to achieve a complete remission (CR) or partial remission (PR) following standard induction therapy, or has relapsed after any duration of CR or PR i. Patients must have measurable disease with bone marrow blasts ?5%at screening b. Relapsed and/or refractory higher-risk MDS (High / Very High Risk, as defined by the Revised International Prognostic Scoring System (IPSS-R)) that has failed to achieve a CR or PR, or any hematologic improvement (HI, per IWG 2006 criteria) after standard therapy with hypomethylating agents (e.g., azacitidine, decitabine), or has relapsed after any duration of CR or PR or HI i. Patients must have measurable disease with bone marrow blasts >5% at screening c. Newly diagnosed, treatment-naïve non-APL AML in patients who, at the time of study entry are unlikely to tolerate standard intensive chemotherapy due to age, performance status, or comorbidities based on at least one of the following criteria (Ferrara et al, 2013): i. Age ? 75 years old ii. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 3 iii. Cardiac history of congestive heart failure (CHF) or documented ejection fraction (EF) ? 50% iv. Pulmonary disease with DLCO ? 65% or FEVI ? 65% v. Creatinine clearance ? 30 mL/min to < 45 mL/min vi. Hepatic impairment with total bilirubin > 1.5 to ? 3.0 x upper limit of normal (ULN) vii. Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy, and reviewed and approved by the Sponsor prior to enrollment d. Transfusion dependent lower-risk MDS without the del 5q abnormality, in patients refractory to erythropoietin treatment or unlikely to respond to erythropoietin treatment (EPO >500). i. Lower-risk MDS: Very Low /Low / Intermediate Risk, as defined by IPSS-R. ii.Red blood cell (RBC) transfusion dependent anemia defined as no eight consecutive weeks without RBC transfusions within the 16 weeks prior to study entry, or ?4 RBC transfusions within the 8 weeks prior to study entry. iii.Refractory to or ineligible for ESAs is defined as RBC-Transfusion Dependence despite ESA treatment of ?40,000 units/week recombinant human erythropoietin for 8 weeks or an equivalent dose of darbepoetin (150 µg/week) or serum EPO level >500 mU/mL in patients not previously treated with ESAs.
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* Recipient age 30 years and older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease \r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Participants who have had a complete response (CR) after pre-study therapy are not eligible for study
Patients with complete response (CR) or stringent CR after induction therapy as defined by International Response Criteria after most recent therapy
Patients with B-lineage ALL in a) hematologic complete remission (CR) beyond CR1 at time of transplant; patients beyond CR1 or with primary induction failure may be without minimal residual disease, b) any residual disease defined by positive flow > 0.01%, detection of breakpoint cluster region-abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) transcript by polymerase chain reaction (PCR) with a sensitivity of 1/10,000, or detection of the t(9;22) translocation in any metaphases by cytogenetics at time of transplant, or presence of the MLL gene
Achieving partial response (PR) or very good partial response (VGPR) with systemic chemotherapy
Patients who achieved complete response (CR) prior to autologous HCT
Continued CR, CRp, or CRi within 3 weeks of first dose WT-1 specific CD8+ T cells
Relapse after minimal residual disease (MRD)-negative CR within 3 months of most recent GCLAM chemotherapy
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* 30 years of age or older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B cell [B]-ALL) or greater than 100,000/mcL (T cell [T]-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease\r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Presence of measurable or evaluable disease (unless patient has achieved a complete response (CR) following first-line antineoplastic therapy).
Patients without measurable or evaluable disease (unless patients achieved a complete response (CR) following 1st-line antineoplastic therapy).
Acute myeloid leukemia: High risk first complete remission (CR1) (as evidenced by preceding myelodysplasia [MDS], high risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT-3 ITD +; second or higher complete response [CR2+]); all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Acute lymphocytic leukemia (ALL): Factor that define high risk CR1 include but are not limited to cytogenetics demonstrating t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD); patients in CR2+ are eligible; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >=15%
Patients with complete response (CR)/very good partial response (VGPR) disease
Patients must have a sustained clinical response (PR, nodular PR [nPR], complete clinical response [CCR], CR with incomplete marrow recovery [CRi], CR) with documented residual disease (>= 1 CLL cell per 10,000 leukocytes or >= 0.01% MRD) either in the blood, bone marrow or a lymph node >= 3.5 cm by any available techniques
Relapsed or refractory B-cell ALL:\r\n* 1st or greater bone marrow (BM) relapse OR\r\n* Any marrow relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and > 100 days from transplant OR\r\n* For patients with refractory disease:\r\n** < 60 years old that have not achieved a complete remission (CR) after > 2 or more chemotherapy regimens\r\n** >= 60 years old that have not achieved a CR after 1 prior chemotherapy regimen
Participants who received at least only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT)
Patients with AML in remission (defined as CR, CR with incomplete platelet recovery –CRp-, CR with incomplete hematologic recovery -CRi-, or partial remission defined as a bone marrow with < 10% blasts after therapy with or without hematologic recovery)
Creatinine (Cr) < 2.0
Acute lymphoblastic leukemia (ALL)\r\n* High-risk CR1 including:\r\n* Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22) or 11q23 rearrangements)\r\n* Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy\r\n* No complete remission (CR) within 4 weeks of initial treatment\r\n* Induction failure\r\n* CR2 or CR3 with either\r\n** =< 10% blasts in the marrow or \r\n** =< 5% blasts in the peripheral blood
Creatinine measurement (Cr) < 1.7
Relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)\r\n* 1st or greater bone marrow (BM) relapse OR\r\n* Any marrow relapse after allogeneic hematopoietic stem cell transplant (HSCT) and > 100 days from transplant OR\r\n* For patients with refractory disease:\r\n** < 60 years old that have not achieved a CR after >= 2 or more chemotherapy regimens\r\n** >= 60 years old that have not achieved a CR after 1 prior chemotherapy regimen\r\n** Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they have failed tyrosine kinase inhibitor therapy
Patients who had anything less than a CR (PR, SD or progressive disease) to their last salvage regimen
Hodgkin lymphoma that is: \r\n* PIF (primary induction failure): did not enter complete remission with first line of therapy; Note: a patient with PIF who responds to salvage therapy with a PR or CR is also eligible (and would be considered PIF-sensitive)\r\n* Early 1st relapse: initial CR of > 3 months and < 12 months after 1st line chemotherapy\r\n* 1st relapsed HL in a patient who is not in CR after 2 cycles of salvage therapy\r\n* In 2nd or subsequent relapse (RL) whether in CR or not after salvage therapy
Creatinine (Cr) < 2.0
Diagnosis of one of the following:\r\n* Previously untreated Ph-positive ALL (either t[9;22] and/or bcr-abl positive) (includes patients initiated on first course of hyper-CVAD before cytogenetics known)\r\n* Previously treated Ph-positive ALL, after 1-2 courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs)\r\n** If they achieved complete response (CR), they are assessable only for event-free and overall survival, or\r\n** If they failed to achieve CR, they are assessable for CR, event-free, and overall survival
Other acute leukemias that are ambiguous lineage or of other types e.g. blastic plasmacytoid dendritic cell neoplasm in CR1 or CR2
Poor Prognosis Non-Seminomas Germ Cell Tumor in >= partial response (PR)1/complete response (CR)1 or Good or Intermediate Prognosis Seminomas and Non-Seminomas Germ Cell Tumor in >= PR1 or >= CR2 as defined by the International Germ Cell Cancer Consensus Classification; Patients with increasing tumor markers only (i.e., no imaging evidence of progressive disease) are eligible for transplant
Acute myeloid leukemia: high risk first complete remission (CR)1 as evidenced by: \r\n* High risk cytogenetics; t(4;11) or other mixed lineage leukemia (MLL) rearrangements; chromosome 5, 7, or 19 abnormalities; complex karyotype (> 5 distinct changes)\r\n* >= 2 cycles to obtain complete remission (CR)\r\n*Second CR (CR2) or higher preceding myelodysplasia (MDS)\r\n* All patients must be in CR or early relapse (i.e., < 15% blasts in bone marrow [BM])
Acute lymphocytic leukemia: high risk CR1 as evidenced by: \r\n* High-risk cytogenetics: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22)\r\n* > 1 cycle to obtain CR\r\n* CR2 or higher\r\n* All patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Patients must be receiving a v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) inhibitor and failed to achieve PR or CR or have progressive disease in response to B-RAF treatment (Cohort C)
Achieves PR or CR in response to B-RAF treatment (Cohort C)
Acute myeloid leukemia (AML): high risk complete response (CR)1 (as evidenced by preceding myelodysplastic syndromes [MDS], high risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >=15%
Acute lymphocytic leukemia (ALL): high risk CR1 as defined by cytogentics (such as t(9;22), t (1:19), t(4;11), other mixed lineage leukemia (MLL) rearrangements, hypodiploidy, or IKZF1 abnormalities), deoxyribonucleic acid (DNA) index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD); patients in CR2+ are eligible; all patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%
Acute myeloid leukemia: high risk first complete remission (CR1) (as evidenced by preceding myelodysplastic syndrome [MDS], high risk cytogenetics such as those associated with MDS or complex karyotype, > 2 cycles to obtain complete response [CR] or erythroblastic and megakaryocytic); second or greater CR
Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22), t(1;19),t(4;11), other mixed-lineage leukemia (MLL) rearrangements, hypodiploidy or IKAROS family zinc finger 1 [IKZF1]), > 1 cycle to obtain CR or evidence of minimal residual disease (MRD); patients in second or greater CR are also eligible
Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\r\n* 30 years of age or older at diagnosis\r\n* White blood cell counts of greater than 30,000/mcL (B-cell [B]-ALL) or greater than 100,000/mcL (T-cell [T]-ALL) at diagnosis\r\n* CNS leukemia involvement during the course of disease\r\n* Slow cytologic response (> 10% lymphoblasts in bone marrow on day 14 of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
>=6 months after completing any line of chemotherapy, or after autologous stem cell transplantation, and having attained either a very good partial response (VGPR) or a complete response (CR), and without the need for haematological maintenance therapies Inclusion Criteria for Group 3
Confirmed free light chain complete response (CR) during the first three cycles of first-line chemotherapy where at least the first cycle has been with cyclophosphamide, bortezomib, dexamethasone (CyBorD).
Creatinine (Cr) =< 1.5 x ULN
105 For DLBCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments., with at least one treatment consisting of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP (14 or 21), R-CHOEP, and DA-REOCH. For FL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, R-CVP, and BR. For MCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, BR and hyper-CVAD alternating with R-MTX/Ara-C. For subjects with refractory B-NHL and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy
COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one of the following disease subtypes:\r\n* Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia Network [ELN]) at presentation\r\n** Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p, complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose samples have mutations in RUNX1 or ASXL1 are also eligible (unless the patient has favorable cytogenetics)\r\n* AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction [PCR] for NPM1, core-binding factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry \r\n* AML not in CR1 (including patients with morphologic CR but with incomplete recovery, CRi)\r\n* Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53 mutation, or JAK2 or RAS mutation\r\n* Treatment-related MDS or AML\r\n* Acute lymphoblastic leukemia (ALL) not in CR1\r\n* ALL with MRD\r\n* Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant\r\n* Multiple myeloma\r\n* Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant\r\n* Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse > 80% based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate
Must have achieved CR/CRi with less than 2 induction regimens that contain cytarabine and anthracycline
Patients with: A) diffuse large B-cell lymphoma (DLBCL) with one of the following: A.1) primary refractory (no CR to 1st line), A.2) high-risk relapse (CR1 < 6 months (mo), secondary International Prognostic Index [IPI] >1, high lactate dehydrogenase [LDH]), A.3) refractory relapse: no response to >= 1 salvage line and not eligible to receive other novel salvage therapies, such as chimeric antigen receptor T-cells (CAR-T) in a timely fashion or have already failed these; B) Hodgkin’s with one of the following: B.1) primary refractory (no CR or progressive disease [PD] within 3 months), B.2) high-risk relapse (CR1 < 1 year, extranodal relapse, B symptoms), B.3) refractory relapse: no response to >= 1 salvage line C) T-non Hodgkin's lymphoma (T-NHL) with one of the following: C.1) primary refractory (no CR to 1st line), C.2) high-risk relapse (within 6 months), C.3) refractory relapse to >= 1 line of salvage. D) any other lymphoma that is refractory or relapsed and that does not qualify for autologous transplant protocols of higher priority.
Any curable cancer with a complete response (CR) of > 2 years duration.
Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those patients proceeding to Arm G transplant)
Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
Pediatric patients must have a hematological malignancy as described below:\r\n* AML: high risk CR1 (preceding MDS, intermediate to high risk cytogenetics, >= 2 cycles to obtain CR, French-American-British classification system [FAB] M6); CR2+, first relapse with < 25% blasts in bone marrow; morphologic complete remission with incomplete blood count recovery; therapy-related AML for which prior malignancy has been in remission for at least 12 months\r\n* ALL: high risk CR1 (Philadelphia chromosome positive [Ph+] ALL, MLL rearrangements with slow early response, hypodiploidy, end of induction M3 bone marrow, end of induction M2 with M2-3 at day 42, evidence of minimal residual disease [MRD]); high risk CR2 (Ph+ALL, bone marrow relapse < 36 months from induction, T-lineage relapse at any time, very early isolated central nervous system (CNS) relapse, slow induction after relapse at any time, evidence of MRD); >= CR3\r\n* NK cell lymphoblastic leukemia in any CR\r\n* Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than 25% blasts in bone marrow\r\n* Myelodysplastic syndrome (MDS) at any stage\r\n* Chronic myelogenous leukemia (CML) in chronic or accelerated phase\r\nEvidence of CNS leukemia must be treated and in CNS CR to be eligible for the study
Subjects with a prior diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification who did not achieve complete response (CR) with their previous therapy or who have relapsed after achieving a complete response (CR) are eligible; any number of relapses will be eligible
Patients must be within 2 years of achieving CR following chemotherapy
Creatinine [Cr] < 2.0
Diffuse large B-cell lymphoma\r\n* All patients will be eligible in >= second complete remission (CR2) or >= first partial response (PR1)\r\n* Patients with a high intermediate or high International Protein Index (IPI) (>= 2 for age-adjusted IPI or >= 3 for IPI) at diagnosis will be eligible in first CR
For stage I/II patients treated with primary radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
Acute myelogenous leukemia\r\n* CR #1 and “high-risk” (excludes t[8;21], t[15;17], or inv[16])\r\n* CR #2 or greater
Acute lymphocytic leukemia\r\n* CR #1 + “high-risk” (t[9;22] or bcr-abl+; t[4;11], 1[1;19], t[8;14])\r\n* In CR #2 or greater
Subject must have achieved a CR/CRi/CRp (criteria as defined by [Cheson et al, 2003], see Section 5.3) with first line treatment and has hematologic relapse.
Achieved a response of stable disease, partial response, or complete response following the last cycle of frontline treatment. In addition, patients must have relapsed less than or equal to 6 months from the completion of frontline therapy at the time of initial dosing in this clinical trial.
Patient must have clinical complete response or partial response following completion of chemotherapy course.
Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
Refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapse leukemia OR
Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but are not counted as a line of treatment.
Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but are not counted as a line of treatment.
Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia OR.
Have achieved CR/CRi following therapy with hypomethylating agents
History of a non-CLL malignancy except for adequately treated in situ, stage 1 or 2 carcinoma in Complete Response (CR), or any other cancer that has been in CR for >=2 years after end of cancer treatment.
Relapsed patients must have achieved a complete remission (CR) or CR with incomplete blood count recovery (CRi) lasting < 6 months with their last induction regimen
Patients must have achieved CR; patients who achieved only CRi or PR, and patients who relapse from CR before this registration are not eligible
Creatinine ? 1.5 x ULN or Cr Cl > 60 cc/min
Received at least four treatments with MK-3475 beyond the date when the initial complete response (CR) was declared
Any curable cancer with a complete response (CR) of > 5 years duration.
Subjects treated with prior ipilimumab must have had partial response (PR), complete response (CR), or at least 6 months of stable disease followed by disease progression.
Subjects with metastatic breast cancer who have achieved stable disease (SD), partial response (PR), or complete response (CR) after at least 1 regimen of anticancer therapy (i.e. chemotherapy or target therapy, either alone or in any combination). Involvement of supraclavicular lymph node is considered metastasis.
Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be continued if distant metastases are non-responsive (i.e. no complete response [CR] or partial response [PR]) on that regimen for >= 8 weeks as assessed by the investigator
CR, partial response (PR) or stable disease (SD) after Step 1
Patients with complete response (CR)/very good partial response (VGPR) disease
Histologically or cytologically confirmed extensive-stage disease small cell lung cancer (ED SCLC) with ongoing clinical benefit (stable disease [SD], partial response [PR], or complete response [CR]) following completion of 4 cycles of first-line platinum-based therapy
Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial response (PR) if FIC is to be used
Chemotherapy-sensitive lymphoma in status other than 1st CR
For arms A and B, participants must have relapsed after or been refractory to first-line chemotherapy, i.e., they must have failed to achieve CR after first-line therapy or must have relapsed subsequently if they achieved CR; for arm C, participants will be eligible if transplant is performed as consolidation of first remission (partial or complete)
Be actively receiving duvelisib monotherapy on the previous study (within 14 days of study entry) and demonstrating clinical benefit (complete response [CR]/ partial response [PR]/ stable disease [SD]) of continued use, or
Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.
Creatinine (Cr) < 3
Early first relapse (< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
A very good partial response (VGPR) or better after induction therapy with/without consolidative high-dose therapy/autologous stem cell transplantation (HDT/ASCT).\r\n* Very good partial response (VGPR): \r\n** Serum and urine M-component detectable by immunofixation but not on electrophoresis or\r\n** >= 90% or greater reduction in serum M-component plus urine M-component < 100 mg per 24 hours (h)\r\n* Complete response (CR):\r\n** Negative immunofixation of serum and urine and\r\n** Disappearance of any soft tissue plasmacytomas and\r\n** < 5% plasma cells in bone marrow\r\n* Stringent complete response (sCR)\r\n** CR as defined above plus\r\n** Normal free light chain ratio and\r\n** Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence\r\n* MRD positive by flow cytometry
receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a
During dose escalation, patients must have received at least one prior therapy, need additional cytoreduction, and meet criteria for relapsed or refractory disease; relapsed disease is defined as a patient who previously achieved a CR or a PR, but after a period of six or more months demonstrates evidence of disease progression; refractory disease is defined as progression within six months of the last anti-leukemic therapy, or any response less than a CR or PR; patients who are previously untreated, and do not wish to receive chemotherapy or immunotherapy, are eligible for the dose expansion portion of the study
Subjects must have entered the Maintenance Phase and are under ongoing maintenance treatment or subjects who stopped maintenance treatment because of a complete response (CR) or subjects with an initial partial response (PR) or CR or at least 3 months of stable disease (SD) on tumor assessment and who subsequently have a confirmed and documented disease progression (per immune-related Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
Enrolled in University Of Minnesota study MT2001-10 “Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy” and fitting into one of the following disease categories:\r\n* Acute myelogenous leukemia - high risk first complete remission (CR1) (as evidenced by preceding myelodysplastic syndrome [MDS], intermediate to high risk cytogenetics, >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; second complete remission (CR2)+; all patients must be in CR as defined by hematological recovery (absolute neutrophil count [ANC] > 0.5 x 10^9/L), AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%\r\n* Acute lymphocytic leukemia - high risk CR1 [t(9;22), t (1:19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements] or > 1 cycle to obtain CR; CR2+; all patients must be in CR as defined by hematological recovery (ANC > 0.5 x 10^9/L), AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15%\r\n* Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible)\r\n* Non-Hodgkin lymphoma or Hodgkin’s lymphoma demonstrating chemosensitive disease\r\n* Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections
Cohorts 1 and 3: Participants must have stable disease or be responders (partial response [PR] or complete response [CR]) to neratinib in the CNS at the time of non-CNS progression
CLL patients with evidence of residual disease, who have achieved partial response (PR), nodular partial response (nPR) or complete response (CR) with detectable minimal residual disease (MRD) following upfront therapy consisting of pentostatin, cyclophosphamide and rituximab\r\n* The presence of MRD will be assessed by the flow cytometry and polymerase chain reaction at the Memorial Sloan Kettering Cancer Center (MSKCC) Diagnostic Molecular Pathology Laboratory
Acute lymphocytic leukemia\r\n* Adult: (>= 22 years) >= second complete remission (CR2) OR first CR (CR1) with a high risk feature:\r\n** Matched sibling donor for recipient treated on adult leukemia regimen\r\n** t(9:22) or breakpoint cluster region (bcr)-Abelson (abl)+; t(4:11), t(1:19), t(8:14), 11q23 (mixed lineage leukemia [MLL] rearrangements) complex cytogenetics (5 or more chromosomal abnormalities), hypodiploidy (< 44 chromosomes.; note that patients with acute lymphoblastic leukemia (ALL) blast crisis who emerge from chronic myelogenous leukemia (CML) are also eligible\r\n** Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy\r\n** High white blood cell (WBC) (> 30,000 for B-cell ALL and > 100,000 for T-cell ALL) at diagnosis\r\n** Persistence of minimal residual disease despite induction chemotherapy\r\n* Pediatric (< 22 years): >= CR2 OR CR1 with high risk features\r\n** Matched sibling donor for recipient treated on adult leukemia regimen\r\n** Primary induction failure (M3 [> 25% with greater 200 cells counted] marrow at day 29), M2 (5-25% blasts with greater than 200 cells counted) bone marrow or minimal residual disease (MRD) > 1% at day 29 who then fail at day 43 with either M2 or M3 bone marrow (BM) or MRD > 1%\r\n** Persistent leukemia and t(9;22) (MRD > 1% day 29 or MRD > 0.01% end-consolidation)\r\n** 11q23 (MLL) rearrangements detected by cytogenetic or polymerase chain reaction (PCR) at initial diagnosis who are slow early responders (M2/M3 at day 14 or MRD > 0.01% at day 29)\r\n** Extreme hypodiploidy (< 44 chromosomes or deoxyribonucleic acid [DNA] index of < 0.81) detected by cytogenetic/ploidy analysis
Best response achieved was ?Partial Response (PR)
Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months
Patients must have B-ALL refractory, relapsed, minimal residual disease (MRD), or in first complete remission (CR) as described below\r\n* Complete remission is defined as restoration of normal hematopoiesis with a neutrophil count > 1,000 x 10^6/L, a platelet count > 100,000 x 10^6/L, and hemoglobin > 10 g/dL; blasts should be < 5% in a post-treatment bone marrow differential; furthermore, there should be no clinical evidence of leukemia for a minimum of four weeks\r\n* MRD is defined as patients meeting the criteria for CR above, but with residual disease measured by a quantitative polymerase chain reaction (qPCR), or by flow, or by deep-sequencing of the immunoglobulin heavy chain (IgH) rearrangements; the assay from blood and/or bone marrow defines MRD by qPCR as a cycle threshold (CT) that is at least 1 CT value < than the lowest CT value from the background; outside laboratory tests may suffice for this assessment at the discretion of the principal investigator\r\n* Relapsed B-ALL will be defined as patients that meet the above criteria for a CR before developing recurrent disease (increased bone marrow blasts); refractory patients will be defined as patients that have not achieved a CR after 1 cycle of induction chemotherapy
Patients who have stable (SD) or responding disease (PR or CR) documented by the appropriate radiological, clinical, or laboratory assessments within 12 weeks before enrollment (Note: response criteria from the previous AG-013736 protocol should be used to determine stable or responding disease).
Mantle cell NHL must be beyond first complete response (CR)
Must have achieved a minimum response of partial response (PR, nPR, CRi, CR, and MRD-negative CR) (IWCLL guidelines for the diagnosis and treatment of chronic lymphocytic leukemia [Hallek, 2008]) following completion of second-line induction therapy prior to randomization (documentation of response status must be available). Second-line induction therapy must be documented to have been of sufficient duration.
Diagnosis of one of the following: Previously untreated Ph-positive ALL [either t(9;22) and/or bcr-abl positive] (includes patients initiated on first course of hyper-CVAD before cytogenetics known) These groups will be analyzed separately. After 1-2 courses of chemotherapy with or without imatinib mesylate (Gleevec) · If they achieved CR, they are assessable only for event-free and overall survival, or · If they failed to achieve CR, they are assessable for CR, event-free, and overall survival. Patients with relapsed Ph-positive ALL or lymphoid blast phase of CML.
Creatinine (Cr) =< 2.0
Refractory B-ALL, defined by not having achieved a CR or CRi after two attempts at remission induction using standard regimens, or
Patient has achieved CR or partial response (PR) per per investigator's assessment following completion of CHOP-based therapy and has had radiological assessment within 21 days prior to randomization.
ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after CHOP-based therapy
No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )
Must be within 75 days of completion of first-line treatment regimen; must have achieved complete response (CR/unconfirmed complete response [CRu]) to first-line treatment
If CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or a slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; Note: CR requires complete disappearance of all enhancing abnormalities on gadolinium-enhanced MRI; if CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; for CRu, some patients will have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; it is often difficult to ascertain whether this represents a residual nidus of tumor or scar tissue; if the abnormality does not change or slowly involutes without therapy and corticosteroids, it is reasonable to categorize as a CRu; at the time CR/CRu is determined, the patient should not have used corticosteroids for at least two weeks
Multiple myeloma\r\n* No prior auto hematopoietic transplantation (HCT) fitting into one of the following categories:\r\n** Early disease stage (first complete response [CR1]/first partial response [PR1]) with high-risk molecular features:\r\n*** By FISH or cytogenetics:\r\n**** t(4;14)\r\n**** t(14;16) \r\n**** t(14;20)\r\n**** -17 or -17p\r\n**** -1p or +1q\r\n*** By cytogenetics:\r\n**** -13 or -13q\r\n*** By gene expression profile (GEP):\r\n**** High risk GEP\r\n** Early disease stage (CR1/PR1) with high-risk clinical features:\r\n*** Plasma cell leukemia at presentation\r\n*** Poor count recovery after chemotherapy, making collections from autologous HCT unlikely to be adequate\r\n** Late disease stage (CR2/second partial response [PR2+]) with high- risk clinical features\r\n*** Minimal (< 50% reduction of serum M protein or free light chains, or if non-secretory, < 50% reduction in marrow plasma cell burden) response or progression after therapy with at least two novel agents, including lenalidomide and bortezomib, who demonstrates chemosensitivity to any other salvage regimen\r\n*** Poor count recovery after chemotherapy, making collections for autologous HCT unlikely to be adequate
Relapsed or refractory AML, defined as either: recurrence of disease after a complete remission (CR), or failure to achieve CR with initial therapy.
Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance
Any curable cancer with a complete response (CR) of > 5 years duration.
Creatinine (Cr) > 2.5
Patients with a complete response (CR) to their previous regimen must have a cancer antigen (CA)-125 within normal range; this criterion is not applicable to patients who enroll with a partial response (PR) to their previous regimen
The patient has achieved a first or second CR or CRi. For patients without evidence of MRD in CR/CRi, CR (or CRi) must have been initially identified within 12 months prior to screening. OR The patient has achieved first or second CR or CRi with evidence of MRD as determined locally at least 6 months post stem cell transplant without evidence of acute or chronic graft-versus-host disease post-transplant and has not received immunosuppressant therapy for at least 14 days prior to SL-401 therapy.
Completed and recovered from all planned induction and consolidation therapy according to the institution's standard of care, and achieved a complete remission (CR)/CR with incomplete platelet recovery (CRp); either first or second CR.
Subjects who have received prior bendamustine are eligible if they achieved a response (CR/PR) which lasted > 6 months after the end of bendamustine containing treatment.
Cr ? 2X ULN
Cr ?2X the ULN
The patient is in complete remission (i.e. CR1, CR2, …):
Patients with: diffuse large B-cell lymphoma (DLBCL) with one of the following:\r\n* Primary refractory (no complete response [CR] to 1st line); \r\n* High-risk relapse (CR1 < 6 months, secondary international prognostic index [IPI] > 1 or high lactate dehydrogenase [LDH]); or, \r\n* Refractory relapse: no response (stable disease [SD] or progressive disease [PD]) to >= 1 line of salvage
Hodgkin’s with one of the following: \r\n* Primary refractory (no CR to 1st line or PD within 3 months);\r\n* High-risk relapse (CR1 < 1 year, extranodal relapse or B symptoms); or, \r\n* Refractory relapse: no response (SD or PD) to >= 1 line of salvage
Willingness to participate in CR program
Patient must have had a complete response (CR)/partial response (PR)/stable disease (SD), 4-6 weeks after completing last fraction of radiation therapy
Patients with acute undifferentiated, biphenotypic, or bilineal leukemia, which is in 1st or greater complete remission (CR) or partial remission (PR):\r\n* Cr will be defined as an M1 marrow (< 5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L; cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment; CR without platelet recovery (CRp) will be considered complete remissions); PR will be defined as an M2 marrow (5-19% blasts), no evidence of extramedullary disease, and an absolute neutrophil count >= 1.0 x 10^9/L); cases where the ANC is < 1.0 x 10^9/L and rising will also be considered; the PI will need to approve such cases for enrollment\r\n* Chronic myelogenous leukemia (CML):\r\n** Chronic phase with resistance to tyrosine kinase inhibitors\r\n** Accelerated phase (development of cytogenetic abnormality in addition to t(9:22), blood blast percentage >= 10, blood basophil percentage >= 20, platelet count < 100,000 X 10^9/L)\r\n** Blast crisis\r\n** 2nd or greater chronic phase\r\n* Acute Lymphoblastic Lymphoma in 2nd or greater complete remission:\r\n** Complete remission includes confirmed complete response (CR) defined as the disappearance of all evidence of disease from all sites for at least 4 weeks; bone marrow and cerebrospinal fluid (CSF) must be normal and any macroscopic nodules in any organs detectable on imaging techniques shall no longer be present; imaging should include positron emission tomography (PET) scanning; CR will also include unconfirmed complete responses defined as a residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by > 75% in sum of the products of the greatest perpendicular diameters (SPD), or any residual lesions in organs that have decreased by > 75%, with a negative PET scan, negative bone marrow and CSF\r\n* Peripheral T cell lymphoma (PTCL):\r\n** In first response (must have at least a partial response)\r\n*** PTCL, unspecified\r\n*** Hepatosplenic gamma-delta T cell lymphoma\r\n** Recurrent PTCL (must be treatment sensitive with at least a partial response); if patient has had a previous autologous transplant, the melphalan and fludarabine conditioning regimen must be utilized\r\n** Chronic myelomonocytic leukemia\r\n** Atypical (breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 [BCR-ABL] negative) chronic myelogenous leukemia\r\n** Hodgkin lymphoma that has recurred or progressed after an autologous BMT\r\n*** Newly diagnosed or recurrent disease initially refractory to intensive chemotherapy; a partial response or better must be achieved prior to transplantation; eligibility of newly diagnosed cases must be discussed with the study principal investigator (PI)\r\n*** Disease that has recurred or progressed after an autologous BMT; salvage chemotherapy must produce a partial response or better; the melphalan and fludarabine conditioning-regimen must be used for these patients\r\n** Non-Hodgkin lymphoma other than lymphoblastic or peripheral T cell lymphoma\r\n*** Newly diagnosed or recurrent disease initially refractory to intensive chemotherapy; a partial response or better must be achieved prior to transplantation; eligibility of newly diagnosed cases must be discussed with the study PI\r\n*** Disease that has recurred or progressed after an autologous BMT; salvage chemotherapy must produce at least a partial response; the melphalan and fludarabine conditioning-regimen must be used for these patients
Spot urine Ca:Cr ratio >0.25 (>250 mg/g creatinine)
(Part B only) Histologically confirmed DLBCL/MCL/FL/PTCL/MF/CLL on the basis of excisional lymph node or extranodal tissue biopsy; diagnosis of relapsed/refractory disease defined as 1) recurrence of disease after a Complete Response (CR), or 2) Partial Response (PR), Stable Disease (SD) at completion of treatment regimen preceding entry into study, subjects must not be candidates for standard therapy, subjects who have not received Stem Cell Translplant (SCT) must be ineligible to receive SCT.
Patient must be scheduled to undergo stem cell transplantation for one of the following diagnoses: \r\n* Acute myeloid leukemia (AML) in first complete remission (CR1) (first complete remission, CR or CR with incomplete blood count recovery [CRi]) or second complete remission (CR2) (second complete remission, CR or CRi) \r\n* Acute lymphoblastic leukemia (ALL) in CR1 or CR2, (CR or CRi)\r\n* Myelodysplastic syndrome (MDS) without progression to AML \r\n* Chronic myelogenous leukemia (CML)\r\n* Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease (HD)\r\n* Chronic lymphocytic leukemia (CLL)\r\n* Multiple myeloma (MM)
Patients with benign hematologic disorders such as severe aplastic anemia do not have disease response requirements; patients with a malignant hematologic disorder must be in complete response (CR) (MRD is allowed) with the exception of the following:\r\n* Patients with MDS/MPN only require < 5% myeloblasts on bone marrow evaluation\r\n* Patients with AML or ALL may be in complete remission with incomplete marrow recovery (CRi), patients with MM may be in very good partial response (VGPR)
Multiple myeloma in CR/very good partial response (VGPR)
Prior or ongoing response (IWG 2006: HI, PR, CR, or marrow CR) to treatment with azacitidine for injection or decitabine, at any time in the subject's prior history, which includes relapsed disease
Creatinine (Cr) > 2.0
Creatinine (Cr) =< 1.5
Subject has confirmed morphologically documented AML, excluding acute promyelocytic leukemia (APL), in CR1 (including CRp and CRi). For the purposes of enrollment, CR will be defined as < 5% blasts in the bone marrow with no morphologic characteristics of acute leukemia (e.g., Auer rods) in the bone marrow with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
Has relapsed (disease progression after most recent therapy) or refractory (failure to achieve Complete Response [CR] or Partial Response [PR] to most recent therapy) classical Hodgkin Lymphoma.
Acute Myelogeneous Leukemia (AML) in CR1 that is NOT considered as favorable-risk. Favorable risk is defined as having one of the following: t(8.21) without CKIT mutation, inv(16) without CKIT mutation or t(16;16), normal karyotype with mutated NPM1 and not FLT-ITD, normal karyotype with double mutated CEBPA, Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation
Acute myeloid leukemia (AML): second or greater complete remission (CR); first CR (CR1) in patients >= 60 years old; CR1 in < 60 years old that is NOT considered as favorable risk\r\n* Favorable risk AML is defined as having one of the following:\r\n* t(8,21) without cKIT mutation\r\n* inv(16) or t(16;16) without cKIT mutation\r\n* Normal karyotype with mutated NPM1 but FLT3-ITD wild type\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Acute myeloid leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in =< 60 years old that is NOT considered as favorable-risk; favorable risk AML is defined as having one of the following:\r\n* t(8,21) without cKIT mutation\r\n* inv(16) or t(16;16) without cKIT mutation \r\n* Normal karyotype with mutated NPM1 and wild type FLT-ITD\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Has favorable risk AML as defined by the presence of isolated t(8;21) or inv(16) or t(16;16)(p13.1;q22) on a standard karyotype or mutated NPM1 with concurrent wild-type FLT3 on molecular testing
Acute myeloid leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in =< 60 years old that is NOT considered as favorable-risk; favorable risk AML is defined as having one of the following:\r\n* t(8,21) without cKIT mutation\r\n* inv(16) or t(16;16) without cKIT mutation\r\n* Normal karyotype with mutated NPM1 and wild type FLT-ITD\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk; favorable risk is defined as having one of the following:\r\n* t(8,21) without CKIT mutation\r\n* inv(16) without CKIT mutation or t(16;16)\r\n* Normal karyotype with mutated nucleophosmin (NPM)1 and not fms-related tyrosine kinase (FLT)-IND\r\n* Normal karyotype with double mutated CCAAT enhancer binding protein alpha (CEBPA)\r\n* Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation
Acute myelogenous leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in =< 60 years old that is NOT considered as favorable-risk; favorable risk is defined as having one of the following:\r\n* t(8,21) without cKIT mutation\r\n* inv(16) or t(16;16) without cKIT mutation\r\n* Normal karyotype with mutated NPM1 and wild type FLT-ITD\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at end of consolidation