Patients must have fewer than 20% marrow blasts within 60 days of consent.
Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts from peripheral blood; FISH testing for common B-lineage ALL abnormalities including t(9;22) (BCR/ABL1), t(12;21) (ETS-variant gene 6 [ETV6]/runt-related transcription factor 1 [RUNX1]), t(1;19) (pre-B-cell leukemia homeobox 1 [PBX1]/transcription factor 3 [TCF3]), +4,+10,+17, (centromeric [Cen]4/Cen10/Cen17), t(11q23;var), (myeloid/lymphoid or mixed lineage leukemia [MLL]), deletion (del)(9p) (cyclin-dependent kinase inhibitor 2A [CDKN2A]/Cen9), and t(14;var) (immunoglobulin heavy chain [IGH] is encouraged); if there are few or no circulating blasts and an adequate marrow sample cannot be obtained for cytogenetic analysis, the patient may still enroll on the trial
Patient has one of the following: \r\n* Patients has previously untreated de novo AML and meets the criteria for AML with >= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification\r\n** Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/FISH testing is feasible can be substituted for the marrow exam at diagnosis\r\n* Patients has cytopenias and/or bone marrow blasts but does not meet the criteria for the diagnosis of AML (WHO Myeloid Neoplasm classification) because of < 20% marrow blasts and meets the criteria for a diagnosis of myelodysplastic syndrome (MDS)\r\n* Patients has a history of transient myeloproliferative disorder (which may or may not have required chemotherapy intervention), who:\r\n* Are > 8 weeks since resolution of transient myeloproliferative disease (TMD) with >= 5% blasts, OR\r\n* Patients who have an increasing blast count (>= 5%) in serial bone marrow aspirates performed at least 4 weeks apart
In the event that the patient’s bone marrow blast count is >= 50% blasts, patients may be registered but should receive steroids for 3-5 days in order to reduce tumor burden prior to blinatumomab administration, as follows\r\n* Prephase treatment with dexamethasone (10-20 mg/m^2) for 3-5 days is required for patients with bone marrow blasts >= 50%, peripheral blood blasts 15,000/uL or higher, or elevated lactate dehydrogenase (LDH) suggesting rapidly progressive disease per investigator opinion\r\n** Pre-treatment should conclude at least 24 hours prior to the first dose of blinatumomab (although additional dexamethasone is automatically given as a pre-med prior to the first dose); at the time of first infusion of blinatumomab, the absolute peripheral blast count should be < 25,000/uL\r\n** Note: For the purposes of the study, day 1 of the cycle will be the first day of blinatumomab administration
Patients with MDS must have experienced treatment failure with at least one cycle of hypomethylating therapy or induction therapy and have ? 10% bone marrow blasts
Patients must have evidence of acute leukemia in their peripheral blood or bone marrow; patients must have >= 5% blasts in the peripheral blood or bone marrow within 14 days prior to registration; at least >= 20% of those blasts must be CD22-positive (surface) based on local immunophenotyping and histopathology
Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)-refractory anemia with excess blasts (RAEB) (including chronic myelomonocytic leukemia [CMML] with excess blasts and MDS/myeloproliferative neoplasm [MPN] overlap syndrome) not in remission (defined as >= 5% blast in bone marrow or peripheral blood) prior to leukemia cell harvest; patients may receive additional cytoreductive therapy after leukemia cell harvest and before admission for transplant, , at the discretion of the treating physician; for patients with MDS-EB1 (< 10%blasts) or CMML-1, it is recommended that they proceed directly to transplant after the harvest if donor is available; if there is an extended delay, interval therapy with HMA is allowed\r\n* Patients may or may not have active disease at the time of transplant conditioning, but for reduced intensity conditioning (RIC) candidates, it is strongly recommended that disease is cytoreduced such that the pre-transplant admission marrow shows:\r\n** < 30% blasts in a normocellular marrow (>= 50% cellularity), or\r\n** < 50% blasts in a hypocellular marrow (< 50% cellularity)
Myelodysplasia (MDS)/myeloproliferative syndrome (MPS): patients must have < 5% marrow blasts at time of transplant
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
Presence of >= 5% circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with MDS/MPS
Hyperleukocytosis with ? 30,000 leukemic blasts/µL blood (hydroxyurea permitted up to 24 hours prior to beginning study drugs)
MDS - Marrow blasts must be > 5% and disease failed at least 1 prior hypomethylating agent
More than 5% blasts in bone marrow
Patients must have IPSS score determined by cytogenetic analysis prior to randomization; patients with cytogenetic failure and =< 10% marrow blasts will be eligible
Participant with lymphoma must meet one of the following:\r\n* In first relapse, OR\r\n* Refractory to one or two courses of frontline induction therapy with measurable disease\r\n* Relapse in ALL is defined as the reappearance (in a patient who has previously achieved remission) of leukemic blasts in the bone marrow or peripheral blood\r\n** Should flow cytometric analyses suggest relapse (by the reappearance of a similar immunophenotype to the original leukemia) in the presence of < 5% blasts morphologically, a repeat bone marrow test is recommended to confirm relapse\r\n** Molecular or genetic relapse is characterized by the reappearance of a cytogenetic or molecular abnormality\r\n** Early relapse is defined as relapse on therapy or < 6 months after completion of frontline therapy; late relapse is defined as relapse occurring >= 6 months after completion of frontline therapy
Fewer than 20% blasts in the bone marrow or peripheral blood
Had accelerated phase or leukemic transformation (>= 10% blasts in peripheral blood [PB] or bone marrow [BM] any time prior to HCT)
Peripheral blood blasts ? 10%
Prior chemotherapy for AML. Hydroxyurea is allowed for the control of peripheral leukemic blasts in subjects with leukocytosis
Morphological disease in the bone marrow (? 5% blasts)
Bone marrow blasts of at least 10%
Patient must be diagnosed with acute leukemia in morphologic complete remission (CR1 or CR2) or with MDS with no circulating blasts and with less than 5% blasts in the bone marrow
Patients who are currently undergoing or who previously underwent allogeneic HCT for \r\n* Acute myeloid leukemia (AML) of any subtype and any of the following:\r\n** With relapse or refractory disease (>= 5% marrow blasts by morphology, or circulating blasts, chloroma or granulocytic sarcoma) at the time of the pre-HCT work-up\r\n** With minimal/measurable residual disease (MRD: defined as detectable disease by morphology, flow cytometry, molecular or cytogenetic testing but < 5% marrow blasts by morphology, no circulating blasts) at the time of the pre-HCT work-up\r\n** With marrow aplasia or marked hypoplasia (bone marrow cellularity =< 10%) following chemotherapy for prior refractory AML at the time of the pre-HCT work-up\r\n** With relapse or refractory disease (>= 5% marrow blasts by morphology, or circulating blasts) at any time after HCT\r\n** With MRD at any time after HCT\r\n* Acute lymphoid leukemia (ALL) of any subtype and any of the following:\r\n** With relapse or refractory disease (>= 5% marrow blasts, or circulating blasts) at the time of the pre-HCT work-up\r\n** With MRD at the time of the pre-HCT work-up\r\n** With marrow aplasia or marked hypoplasia (bone marrow cellularity =< 10%) following chemotherapy for prior refractory ALL at the time of the pre-HCT work-up\r\n** With relapse or refractory disease (>= 5% marrow blasts, or circulating blasts) at any time after HCT\r\n** With MRD at any time after HCT\r\n* Biphenotypic/undifferentiated/any other type of acute leukemia and any of the following:\r\n** With relapse or refractory disease (defined as detectable disease by morphology, flow cytometry, molecular or cytogenetic testing but < 5% marrow blasts by morphology, no circulating blasts) at the time of the pre-HCT work-up\r\n** With MRD at the time of the pre-HCT work-up\r\n** With marrow aplasia or marked hypoplasia (bone marrow cellularity =< 10%) following chemotherapy for prior refractory acute leukemia at the time of the pre-HCT work-up\r\n** With relapse or refractory disease (>= 5% marrow blasts, or circulating blasts) at any time after HCT\r\n** With MRD at any time after HCT \r\n* Chronic myeloid leukemia with a history of blast crisis and \r\n** With relapse or refractory disease (>= 5% marrow blasts, or circulating blasts) at any time after HCT\r\n** With persistent rising minimal residual disease (defined as detectable disease by morphology, flow cytometry, molecular or cytogenetic testing but < 5% marrow blasts by morphology, no circulating blasts on >= 2 of two consecutive tests), refractory or ineligible for treatment with tyrosine kinase inhibitors at any time after HCT
Confirmation of ‘measurable disease’ by blast % will be defined as a marrow blast percentage of > 5% by morphologic assessment on bone marrow examination; this criteria does not apply to myeloid sarcoma which must also show measurable lesion by computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT or photograph (i.e. Leukemia cutis); if marrow blasts of =< 5% blasts are enumerated the patient may be eligible only if there is clear (probable or definite) flow cytometric, cytogenetic or molecular aberrations (e.g. FLT3-ITD, NPM1, etc.) documenting relapse of the leukemia associated clone defined prior to HCT
Presence of circulating blasts (in the blood) detected by standard pathology for patients with AML, ALL or CML
Presence of >= 5% circulating leukemic blasts (in the blood) detected by standard pathology for patients with MDS/MPS/CMML
Must have a diagnosis of chronic phase (CP) (defined as peripheral blood and bone marrow < 10% blasts) primary myelofibrosis (PMF) or post essential thrombocythemia (post-ET) or polycythemia vera (post-PV) myelofibrosis by World Health Organization (WHO) criteria OR a diagnosis of a myeloproliferative neoplasm in accelerated/blast phase (MPN-AP/BP) defined as either a peripheral blood or bone marrow with >= 10% blasts
Use of hydroxyurea is permitted to control blasts until day -3
AML ONLY: AML with > 30% circulating blasts and > 50% bone marrow blasts
Acute leukemias: Must be in remission by morphology (< 5% blasts); NOTE: cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration versus (vs.) early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
No blasts or promyelocytes in peripheral blood
Patients with AML must have less than 10% bone marrow blasts and < 100/mcL absolute peripheral blood blast count
For subjects with ALL or AML, presence of >5% blasts in the bone marrow (based on a bone marrow aspirate/biopsy sample with ?200 nucleated cells and the presence of bone marrow spicules) and/or >1 x 109/L blasts in the peripheral blood (with the restriction that peripheral blast count in subjects with AML must be <50 x 109/L prior to the start of study therapy).
Blasts in Peripheral Blood or Bone Marrow ?15% (either myeloid or lymphoid blasts)
Promyelocytes and Blasts in Peripheral Blood or Bone Marrow ?30%
Cytogenetic clonal evolution Blast phase is defined as ?30% blasts in peripheral blood or bone marrow, or presence of extramedullary disease, except for liver or spleen.
Relapsed ALL defined as > 5% malignant blasts in bone marrow or peripheral blood
Diagnosis of relapsed or refractory AML, ALL, acute biphenotypic leukemia (assigned to the appropriate group by the treating physician and pathology/cytogenetics), advanced MDS defined as ?10% bone marrow blasts, advanced MPN, MDS/MPN overlap syndrome with ?10% bone marrow blasts, or advanced CML after failure of at least 3 TKIs
Diagnosis of relapsed or refractory AML, ALL, acute biphenotypic leukemia (assigned to the appropriate group by the treating physician and pathology/cytogenetics), advanced MDS defined as ?10% bone marrow blasts, advanced MPN, MDS/MPN overlap syndrome with ?10% bone marrow blasts, or advanced CML after failure of at least 3 TKIs
Acute leukemias: Must be in remission by morphology (< 5% blasts); Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
Very high risk pediatric patients with AML: Patients < 21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy
Subjects must have evaluable disease defined as > 5% blasts on marrow aspirate or biopsy, extramedullary disease (central nervous system [CNS] involvement is prohibited), or at least 20% blasts in the peripheral blood within 4 weeks prior to enrollment; Note: subjects with second or subsequent relapse are considered to have evaluable disease even without having > 5% marrow blasts if they are found to have persistent/recurrent disease-associated molecular or cytogenetic abnormalities at any time since their last cycle of intensive chemotherapy
Expectation that we can obtain about 10 million blasts from blood and/or marrow (e.g., circulating blast count of 5,000 or greater or cellular marrow with greater than or equal to 20% blasts)
Disease criteria: day 21 (+/-7 days) bone marrow aspiration or biopsy from the beginning of salvage DCIA: a. in complete morphologic remission with < 5% bone marrow blasts, or b. aplastic (< 10% bone marrow cellularity), and cytopenic with an absolute neutrophil count (ANC) less than 1,000/uL, or c. low disease burden with < 30% bone marrow (BM) blasts, with recovery of peripheral blood (PB) white blood cell (WBC) (ANC > 1,000/uL) and < 5% circulating blasts
For cohort 1 only: patients with a bone marrow biopsy with < 15% cellularity, evidence of collagen fibrosis, osteosclerosis, or blasts > 10% in peripheral blood or marrow (demonstrating advanced disease)
RECIPIENT: Patients may have evidence of MDS with one or more peripheral blood cytopenias and greater than 5% blasts but less than 10% blasts in the bone marrow in the absence of filgrastim
Acute myeloid leukemia who fail to achieve complete remission with one course of induction chemotherapy or after relapse; patients must have less than 20% bone marrow or peripheral blood blasts
Patients with CML-AP or CML-BP or Philadelphia chromosome-positive acute myeloid leukemia defined as follows: CML-AP is defined by the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), >= 20% basophils in PB or BM, >= 30% blasts plus promyelocytes (with blasts < 30%) in PB or BM, < 100 x 10^9/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome); CML-BP is defined by the presence of >= 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease
Aspartate aminotransferase (AST) =< 5 x the institutional ULN, measured prior to conditioning chemotherapy; elevation secondary to leukemic involvement is not an exclusion criterion; leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of known hepatotoxic medication (e.g. azoles)
Presence of less than 20% bone marrow blasts per bone marrow
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 ANC > 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp); if the marrow has < 20% cellularity due to treatment related cytotoxicity, but still has < 5% blasts, an exception may be made to include this patient up to principal investigator (PI) discretion
Myeloproliferative disorder (MPD)\r\n* Life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence\r\n* Patients with aplasia\r\n* Patients with excess blast less than or equal to 10% blasts in the bone marrow at work-up
Myelodysplastic syndrome (MDS): Any subtype; morphologic blasts must be less than 5% in an evaluable marrow (> 25% of normal cellularity for age); if blasts are 5% or more, patient requires induction chemotherapy pre-transplant to reduce blast count to less than 5%; patients who have a hypocellular marrow in the absence of excess blasts that is related to the underlying disease or as a result of treatment for MDS may also be eligible with the approval of the PI or designee
Greater than 30% blasts in bone marrow or greater than 5% in peripheral blood
Very high risk pediatric patients with AML; patients < 21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately
Acute leukemias: must be in remission by morphology (< 5% blasts); note cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible, patients with acute leukemia in morphologic relapse/persistent disease defined as > 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible
Acute leukemias: must be in remission by morphology (=< 5% blasts); also a small percentage of blasts that is equivocal between marrow regeneration versus (vs.) early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
Very high risk pediatric patients with AML: patients < 21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy
<5% blasts in marrow or blood at time of screening
<1% peripheral blood blasts.
<10% bone marrow blasts.
Acute myeloid leukemia-intermediate risk as defined by standard World Health Organization (WHO) criteria for AML (at least 20% blasts in the peripheral blood or bone marrow) at the time of initial diagnosis\r\n* Diagnosis of AML according to WHO diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with French–American–British (FAB) classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy
More than 5% blasts in bone marrow
Presence of >= 5% abnormal blasts in the bone marrow
Have previously untreated AML, defined according to WHO criteria, with ? 20% leukemic blasts in the bone marrow. Subjects with extramedullary disease alone (ie, no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
Bone marrow blasts >5% at randomization, OR
Subjects who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ?20%.
Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts (> 10^9/l) from peripheral blood
Circulating blasts < 20,000 (cytoreduction with hydroxyurea is allowed)
Acute lymphocytic leukemia- high risk CR1 as evidenced by high risk cytogenetics [eg t(9;22) or complex cytogenetic abnormalities] or > 1 cycle to obtain 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 or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible for arms 2 or 3; note cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration vs early relapse is acceptable provided there are no associated cytogenetic markers consistent with relapse
Patients must have > 5% blasts in the bone marrow at the time of study enrollment
Blasts in the peripheral blood (PB) and bone marrow (BM) < 20% prior to study enrollment
Accelerated phase myeloproliferative neoplasm (MPN) as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of acute myelogenous leukemia as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF
Leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).
Relapsed or refractory AML patients with at least 5% blasts by bone marrow biopsy or aspirate, or at least 1% blasts in peripheral blood, not likely to benefit from standard salvage chemotherapy.
MDS: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
CMML: Patients with CMML1 who have not received myelosuppressive therapy must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning; OR patients with CMML who have progressed beyond CMML1 and have received myelosuppressive chemotherapy must have < 5% marrow blasts; fewer than 5% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
MPD: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
Atypical CML: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning
Presence of >= 5% circulating leukemic blasts (in the peripheral blood) detected by standard pathology
Aspartate aminotransferase (AST) =< 5 x the institutional ULN; elevation secondary to leukemic involvement is not an exclusion criterion; leukemic involvement will be determined by the presence of progressive relapsed defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of known hepatotoxic medication (e.g. azoles)
Presence of circulating leukemic blasts in the peripheral blood detected by standard morphology
CMML with 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood. OR Worl health organisation (WHO) Classifications:
RAEB 2 - defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
CMML 2 - defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
CMML 1 (Although CMML 1 is defined as having <10% myeloblasts in the bone marrow and/or <5% blasts in the blood, these participants may enroll only if bone marrow blasts >=5%.
Active AML (bone marrow blasts >= 5% by morphology, staining, or flow) and/or presence of extramedullary disease
Patients with previously untreated primary AML who meet the customary criteria for AML with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible\r\n* Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis
Patients must have measureable disease as defined the presence of >= 5% blasts in bone marrow or extramedullary leukemia
Participants must have a diagnosis of AML or MDS and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)\r\n* Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy\r\n* Patients with AML must have>= 5% leukemic blasts in the bone marrow or increasing levels of minimal residual disease (MRD) in the bone marrow as assessed by flow cytometry; if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood
Morphological disease in the bone marrow (? 5% blasts)
Blast phase disease (> 20% blasts in the marrow or peripheral blood)
Documented excessive leukemic myeloid blasts in the bone marrow or peripheral blood (>= 10%) in the past 6 months
All patients must meet one of the qualifications as outlined below after prior HMA therapy:\r\n* Relapse after CR/CRi or partial remission (PR) - 1 or more of the following:\r\n** Return to pretreatment bone marrow blast percentage (for initial PR)\r\n** Reappearance of bone marrow blasts (> 5%) following initial CR/CRi\r\n* Disease progression\r\n** For patients with 10% to 20% blasts: a 50% or more increase to more than 20% blasts\r\n** For patients with > 20% blasts: a 50% or more increase to more than 40% blasts\r\n* Refractory disease\r\n** No evidence of a response (CR, CRi, PR) following, at least, 6 cycles of hypomethylating agent
Subjects must have a diagnosis of relapsed or refractory ALL with ? 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease. -To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:
Disease refractory or relapsed (defined as the reappearance of > 5% blasts in the bone marrow).
Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow)
Any acute leukemia (including prior myelodysplasia or CML blast crisis) with morphologic relapse or persistent disease >= 10% blasts in the bone marrow (BM), or doubling of the blasts in the blood in the 2 weeks preceding admission, or need for hydroxyurea in the 2 weeks prior to admission, or uncontrolled extra-medullary disease
<5% blasts in blood or marrow at screening
Patients with advanced MDS must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG; less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning; if necessary, a cytoreductive regimen will be determined by referring centers
Patients with MPD must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG; less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning; if necessary, a cytoreductive regimen will be determined by referring centers
Patients with evolution to AML are required to be in a morphologic leukemia-free state with blasts less than 5% in a marrow aspirate; presence of residual dysplastic features following cytoreductive therapy is acceptable
Therapy-related myeloid neoplasms:\r\n* Patients with therapy related-MDS (t-MDS) must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG; less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning; if necessary, a cytoreductive regimen will be determined by referring centers
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
Presence of >= 5% circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with MDS/MPS
Blasts in Peripheral Blood or Bone Marrow ?15%
Promyelocytes and Blasts in Peripheral Blood or Bone Marrow ?30%
Thrombocytopenia <100 x 103/ml, not resulting from therapy Blast phase is defined as ?30% blasts in peripheral blood or bone marrow, or presence of extramedullary disease, except for liver or spleen.
20% blasts in bone marrow
Patients must have obtained a complete remission with chemotherapy defined by the absence of circulating blasts, and less than 5% blasts on bone marrow examination following hematopoietic recovery
Patients must have >= 5% blasts by morphology in the bone marrow OR molecular evidence of at least 0.1% leukemic blasts in the bone marrow
Morphological evidence of disease in bone marrow (at least 5% blasts)
Relapse in ALL is defined as the reappearance (in a patient who has previously achieved remission) of leukemic blasts in the bone marrow\r\n* Should flow cytometric analyses suggest relapse (by the reappearance of a similar immunophenotype to the original leukemia) in the presence of < 5% blasts morphologically, a repeat bone marrow test is recommended to confirm relapse\r\n* Molecular or genetic relapse is characterized by the reappearance of a cytogenetic or molecular abnormality
Patients with T-cell ALL must have greater than 25% blasts in the bone marrow with or without extramedullary disease.
Patients must have received at least one prior chemotherapy regimen for their AML and they may have received any type of chemotherapy; disease relapse or the presence of refractory disease must be documented by bone marrow examination demonstrating > 5% blasts in the bone marrow not attributable to another cause; administration of hydrea to control high white blood cell (WBC) count is permitted
Bone marrow aspirate/biopsy results showing >5% blasts
Remission will be defined as < 5% blasts in the peripheral blood and bone marrow without morphological characteristics of the original leukemia population at the time of diagnosis
Patients with AML in the first morphologic relapse as defined by >= 5% reappearance of leukemia blasts in the bone marrow not attributable to any other cause who have not yet received chemotherapy for the current relapse
Participants must have a diagnosis of AML or MDS and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)\r\n* Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy\r\n* Patients with AML must have >= 5% leukemic blasts in the bone marrow or have converted from negative minimal residual disease (MRD) status to positive MRD status in the bone marrow as assessed by flow cytometry; if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood
Non-M3 acute myeloid leukemia (AML) with the presence of residual disease in the bone marrow on day 14-28 post induction (or re-induction) chemotherapy; day 14-28 residual disease is defined in this study as the presence of more than 10 % blasts in the marrow in patients, presence of between 5-10% blasts cells that are not in cluster in hypocellular marrow is ambiguous and bone marrow biopsy should be repeated in 5-7 days
< 5% blasts in blood or marrow at screening, except if measurable extramedullary AML is confirmed
Leukemic transformation (> 20% blasts in PB or bone marrow [BM] any time prior to hematopoietic cell transplantation [HCT])
Patients must have > 10% leukemic blasts in the bone marrow;
Greater than 5% blasts in bone marrow
Patients must have a strong clinical suspicion of JMML, based on a modified category 1 of the revised diagnostic criteria; specifically, eligible patients must have all of the following: \r\n* Splenomegaly\r\n* Absolute monocyte count (AMC) > 1000/uL\r\n* Blasts in peripheral blood (PB)/bone marrow (BM) < 20%
Relapsed or refractory (resistant) disease, as defined by standard criteria:\r\n* Relapsed: bone marrow blasts >= 5%; reappearance of blasts in the blood; development of extramedullary disease\r\n* Refractory (resistant): failure to achieve CR or CRi in patients who survive >= 7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
Blast phase disease (>20% blasts in the marrow or peripheral blood)
Patients with AML must have less than 30% bone marrow blasts and no peripheral blood blasts
Transformed disease (bone marrow blasts are permitted; however, transformed disease indicating leukemic involvement is not permitted)
Leukemic relapse or disease progression: Patients with > 25% leukemic blasts in the bone marrow will not be eligible for DLI; cytoreduction with chemotherapy is permissible to reduce blast count to =< 25%
Patients must have >= 5% blasts in the bone marrow
Patients must have had histologic verification of AML at original diagnosis; AML is defined according to World Health Organization (WHO) classification with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease
Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with < 5% blasts in the bone marrow (M1) by morphology and that meets one of the following criteria:\r\n* Flow cytometric evidence of minimal residual disease (MRD) (>= 0.1% leukemic blasts for ALL or < 5% leukemic blasts for AML detected in the bone marrow) OR\r\n* Molecular/cytogenetic evidence of disease (fluorescence in situ hybridization [FISH] or polymerase chain reaction [PCR] methodology) performed within 7 days AND\r\n* With the intent of going on to an allogeneic hematopoietic cell transplantation (allo-HCT) independent of this study
Patients must have documented hypoplasia from the bone marrow aspiration and biopsy 14 days +/- 2 days from the initiation of cytarabine treatment schedule (defined as < 5% blasts and < 20% cellularity)
Acute Leukemias: Must be in remission by morphology (< 5% blasts); Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration versus early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
Patients with acute leukemia in morphologic complete remission with or without hematologic recovery or with myelodysplasia (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow. Patients with CMML must have a WBC count ? 10,000 cells/µL and < 5% blasts in the marrow. Patients with ? 5% blasts due to a regenerating marrow must contact the protocol chairs for review.
Subjects with acute leukemia, chronic myelogenous leukemia, or myelodysplasia must have no circulating blasts and < 5% blasts of the bone marrow.
Less than or equal to 5% blasts on bone marrow examination within 60 days of starting conditioning
EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active leukemia (> 5% leukemic blasts in peripheral blood or bone marrow)
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Relapsed leukemia (> 5% leukemic blasts in peripheral blood or bone marrow after allogeneic HCT)
Patients with acute leukemia or chronic myelogenous leukemia with no circulating blasts and with less than 10% blasts in the bone marrow
MDS\r\n* Bone marrow with =< 5 percent myeloblasts with normal maturation of all cell lines\r\n* Peripheral blood demonstrates hemoglobin >= 11 g/dL, platelets >= 100 x 10^9/L, neutrophils >= 1 x 10^9/L, and no circulating blasts
Myelodysplasia (MDS)/myeloproliferative syndrome (MPS) – Patients must have < 5% marrow blasts at time of transplant
Acute leukemias: Must be in remission by morphology (=< 5% blasts); also a small percentage of blasts that is equivocal between marrow regeneration versus early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse
Pre-injectable HMA (HYPOMETHYLATING AGENT) baseline bone marrow myeloblasts: a. Less than 5%: ? 100% increase to ? 8% blasts b. ? 5%: ? 50% increase to ? 10% blasts Note: ? 30% blasts is considered AML (ACUTE MYELOID LEUKEMIAT) per FAB (FRENCH-AMERICAN BRITISH)classification. Subjects known to have ? 30% blasts are not eligible for inclusion in this study. RECOG (Eastern Cooperative Oncology Group) nizing limitations of blast cell quantification, this protocol will allow subjects with pre-enrollment bone marrow blast counts up to 33% on the screening bone marrow examination to be considered for inclusion. Assessment may be made according to local bone marrow examination to facilitate enrollment of eligible subjects into the treatment phase of the study.
Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disorder and myelodysplasia with no circulating blasts and with less than 5% blasts in the bone marrow within 4 weeks of the start of transplant conditioning regimen
Patients with acute leukemia, chronic myelogenous leukemia or myelodysplasia with no circulating blasts and with less than 5% blasts in the bone marrow.
Patients must have obtained a complete remission with chemotherapy defined by the absence of circulating blasts, and less than 5% blasts on bone marrow examination following hematopoietic recovery
The patient has a confirmed diagnosis of Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either CP or AP. Accelerated phase will be defined as disease having 1 of the following: ?15% to <30% blasts in peripheral blood or bone marrow; ?30% blasts + promyelocytes in peripheral blood or bone marrow; ?20% basophils in peripheral blood or bone marrow; platelet count <100x109/L unrelated to therapy; or clonal evolution.
No features suggestive of MDS/AML on peripheral blood smear or bone marrow biopsy, if clinically indicated, within 28 days prior to administration of study treatment
For patients with AML or MDS, patient must have white blood cell count (WBC) ? 50,000/mL. Hydroxyurea is allowed to achieve this change but must be discontinued a minimum of five (5) days prior to baseline evaluation
For AML and MDS patients: patients with a dry tap on bone marrow aspiration during screening
Patients must have previously untreated MDS or AML according to the WHO 2016 classification.
Clinical indication for treatment with azacitidine for MDS or AML.
AML/MDS combination treatment (dose escalation and expansion): histologically or cytologically proven AML or MDS as defined by WHO criteria and IPSS-R, respectively, that is: R/R to standard therapy, or AML: who are unfit for, or unwilling to receive standard induction therapy, or MDS: eligible to receive azacitidine
Known history of MDS or AML
Pathologically confirmed myelodysplastic syndrome (MDS) diagnosis (regardless of initial International Prognostic Scoring System [IPSS] risk category) or oligoblastic acute myeloid leukemia (AML) with 21-30% bone marrow (BM) blasts in whom DNMTi have failed; patients who have developed AML after DNMTi therapy can be enrolled as long as they have initiated DNMTi therapy while they were in the MDS or oligoblastic AML (20-30% BM blasts) phase and the study chair agrees; failure of DNMTis is defined as: failure to achieve a complete response (CR), partial response (PR) or hematologic improvement (HI) after at least 4 cycles of DNMTi or progressed after such therapy
Patients with a diagnosis of acute myeloid leukemia (AML) not transformed from MDS or transformed from MDS with > 30% blasts in bone marrow or white blood cells (WBC) > 25 x 10^3/L
Phase 2 (expansion) subjects must have either MDS or relapsed/refractory AML
A diagnosis of recurrent, persistent, or progressive acute myelogenous leukemia (AML), defined as >= 5% blasts in a patient with known prior history of AML, or recurrent, persistent, or progressive myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria
Patients with the TP53wt hematological tumors (AML, ALL, HR-MDS) who have failed prior therapies or who are considered inappropriate candidates for standard induction therapy.
Patients with MDS who transform to AML while on hypomethylator agents or patients with AML who progress on hypomethylator agents could be considered for arm A of this trial if \r\n* They choose not to be treated on or are ineligible for our competing trial of sEPHB4-HSA + hypomethylator (9L-16-6) \r\n* They are appropriate for high dose cytarabine treatment
Relapsed/refractory AML. Treatment-naive patients who are not eligible for standard induction chemotherapy may also be eligible after discussion with the PI if in the best interest of the patient. Patients with high-risk myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) (defined as >= 10% bone marrow blasts) may also be eligible after discussion with the PI.
Acute myelogenous leukemia (AML):\r\n* Complete first remission (CR1) at high risk for relapse such as any of the following:\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, 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 who elects allograft with curative intent over consolidation chemotherapy.\r\n** Any patient unable to tolerate consolidation chemotherapy as would have been deemed\r\nappropriate 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 AML with less than 10% blasts before transplant. Persistent/relapsed AML with cytogenetic, flow cytometric, or molecular aberrations in >= 10% of cells are eligible.
AML patients with prior history of MDS or CMML who received therapy for the MDS or CMML and progressed to AML, are eligible at the time of diagnosis of AML regardless of any prior therapy for MDS; the World Health Organization (WHO) classification will be used for AML
ARMS A-G: RR AML: Patients with AML who are refractory or relapsed (any salvage) with no available therapies or not candidates for available therapies. For patients with prior MDS or chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm (MPN) who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy for AML.
Patients with previously untreated AML (except acute promyelocytic leukemia [APL]) who have at least one of the following:\r\n* Adverse genetic features as per the European Leukemia Net guidelines\r\n* Treatment related AML or AML with antecedent myelodysplastic syndrome (MDS); (patient who have received treatment with hypomethylating agents for MDS and have now transformed to AML are eligible)\r\n* Are over the age of 55 years and considered fit for chemotherapy\r\n* Patients with AML with MDS-related changes
Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:\r\n* AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)\r\n* AML or ALL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens)\r\n* AML evolved from myelodysplastic or myeloproliferative syndromes\r\n* MDS expressed as refractory anemia with excess blasts (RAEB)\r\n* Chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria
Patients must have a confirmed diagnosis of one of the following:\r\n* Newly diagnosed AML (excluding acute promyelocytic leukemia [APL]) \r\n* Newly diagnosed intermediate-2 (INT-2) or high-risk MDS\r\n* Relapsed or refractory AML, or INT-2 or high-risk MDS
Resolved acute effects of any prior AML/MDS therapy to baseline or ? Grade 1 CTCAE severity.
Patients with AML who are refractory (up to salvage 2) or relapsed (up to 2nd relapse); for patients with prior myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm (MPN) who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy for AML
For patients with newly diagnosed disease: diagnosis of “high-grade” MDS (>= 10% blasts by morphology) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; for patients with relapsed/refractory disease: prior diagnosis of “high-risk” MDS or non-APL AML, with relapsed/refractory disease according to 2003 recommendations of the International Working Group, requiring first or subsequent salvage therapy; patients with mixed phenotype acute leukemia (MPAL) are eligible
May have previously received monotherapy with demethylating agents for MDS or AML or treatment with a mitoxantrone- or cladribine-based regimen for MDS or AML, including G-CLAM, but not demethylating agent as priming for or in combination with chemotherapy
Diagnosis of AML based on 2008 World Health Organization (WHO) criteria; AML may be de novo, following a prior hematologic disorder, including MDS or Philadelphia chromosome-negative myeloproliferative neoplasm, and/or therapy-related
Patients who have received prior chemotherapy for AML with the exception of hydroxyurea or leukapheresis for leukocytosis; prior hypomethylating or immunomodulatory agents for MDS are allowed
Patients with a secondary AML (defined as a history of prior radiation therapy or systemic chemotherapy, antecedent MDS, MPN or CMML)
Untreated secondary AML, including AML that has progressed from myelodysplastic syndrome (MDS)
Newly diagnosed disease with either a diagnosis of “high-risk” MDS (>= 10% blasts in marrow or blood), high-risk myeloproliferative neoplasm (MPN; >= 10% blasts in blood or bone marrow), or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible; such “high-risk” MDS or MPN have natural history much closer to AML than to lower risk MDS or MPN and have responded similarly to “AML-type” therapy
Patient population (histological or cytologically confirmed diagnosis):\r\n* Untreated elderly (> 60 years) AML if in the intermediate and poor-risk cytogenetic group and not candidates (as judged by treating doctor of medicine [MD]) for or willing to undergo standard induction therapy (i.e. elderly unfavorable cytogenetic AML) or any untreated AML age > 65 years\r\n** Note: previous therapy with a hypomethylating agent (HMA) for a diagnosis of MDS is allowed\r\n* Relapsed or refractory AML (>= 18 years)\r\n* Any MDS (>= 18 years) having failed or been intolerant to prior hypomethylating agent (HMA) treatment\r\n** Failure is defined as any disease progression while on HMA, relapse after HMA treatment or no response after 4 cycles of 5-Azacitidine or decitabine\r\n** Patients with isolated 5q-/5q- syndrome must have failed, not tolerated, or lenalidomide in addition to having failed or been intolerant to HMA treatment\r\n*** Note: patients with chronic myelomonocytic leukemia (CMML) and MDS/myeloproliferative neoplasms (MPN) overlap are allowed if meeting other study eligibility criteria\r\n*** Note: for all patient groups, therapy as part of a plan as a bridge to transplant is allowed
Patients must have a diagnosis of acute myeloid leukemia (AML) according to World Health Organization (WHO) criteria; therapy-related and secondary AML (arising after a period of myelodysplastic syndrome [MDS]) allowed; prior treatment for MDS with hypomethylator-based therapy and lenalidomide allowed, but not allowed if used after the diagnosis of AML is made, since enrollment to this study is not for relapsed AML
Prior chemotherapy treatment for AML (prior treatment with hydroxyurea and/or leukapheresis to control white blood cell count, or all-trans retinoic acid [ATRA] for suspected acute promyelocytic leukemia [APML] is acceptable); prior chemotherapy for MDS or myeloproliferative neoplasms (MPN) such as azacitidine, decitabine, and thalidomide, is permitted, but such treatments once MDS or MPN has transformed to AML is not permitted
Phase II FLT3-ITD and/or FLT3-D835 mutated relapsed/refractory patients: patients should have a diagnosis of AML (de novo or transformed from hematologic malignancies); patients with high-risk myelodysplastic syndrome (MDS) (defined as having >= 10% blasts in the bone marrow) or patients with chronic myelomonocytic leukemia (CMML) (having >= 10% blasts in the bone marrow) may also be eligible after discussion with principal investigator (PI); the patients should have one of the following features: 1. patients with AML should have failed any prior induction therapy or have relapsed after prior therapy; 2. patients with high-risk MDS or high-risk CMML should have failed any prior therapy for the MDS or CMML; 3. patients with MDS or CMML who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML
In the phase I portion, patients with relapsed or refractory AML/MDS are also eligible, as per the treating physician’s discretion
Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML; prior therapy for MDS or CMML will not be considered as a prior therapy for AML
In the phase I portion of the study all patients with relapsed or refractory AML are eligible; for the Phase II portion of the study, patients must have AML progressing from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20% blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea are allowed; patients with newly diagnosed or previously treated disease are eligible as long as prior therapy does not include hypomethylating agents; prior therapy for ruxolitinib for MPN is allowed
PHASE II -- Patients aged 60 and older with newly diagnosed primary or secondary AML according to WHO classification, without any prior therapy for AML with the exception of (a) emergency leukapheresis and (b) emergency treatment for hyperleukocytosis with hydroxyurea that is allowed until 24 hours before start of the trial treatment; Note: prior therapy for preexisting hematological condition e.g. MDS or myeloproliferative disease (MPD), including but not limited to hypomethylating agents is allowed until at least 2 weeks have elapsed from completion of that agent before the first dose of MEK 162; patients with relapsed AML, and relapsed MDS and CMML, after prior hypomethylating therapy are also eligible to participate
For Phase I Only: Refractory or relapsed disease defined as follows: Patients with MDS or CMML should have failed prior therapy (e.g., with a hypomethylating agent, clofarabine, and/or with lenalidomide); Patients with AML should have failed any prior induction therapy or have relapsed after prior therapy; Patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML; Patients with any of the eligible diagnoses who have received no prior therapy are eligible if not candidates to receive standard intensive therapy (ie, high-dose cytarabine-based chemotherapy).
For Phase II Only: Patients with MDS, CMML or AML who are either: Age 60 years or older and newly diagnosed, previously untreated. Prior therapy with hydroxyurea or single agent ara-C for the purpose of control of WBC is acceptable.; Age 18 years or older and with refractory or relapse disease who have received no more than one prior treatment regimen and will be receiving first salvage. For this purposes, a second induction cycle with the same drugs used during the first cycle, consolidation chemotherapy or stem cell transplant in CR (or CRp or CRi) will be considered part of the prior regimen. Prior therapy for MDS (or other malignancies) is not considered a prior regimen for AML in patients who progress from MDS (or other malignancies).;
For Phase II only: Patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML
Patients must have a diagnosis of one of the following:\r\n* MDS (Arm A)\r\n** High-risk MDS defined as: > 5% blasts in bone marrow and/or the following cytogenetic categories: presence of inv(3)/t(3q)/del(3q), -7/del(7q), complex cytogenetics (3 or more abnormalities)\r\n* AML (Arm B)\r\n** Relapsed/refractory/unable to tolerate conventional chemotherapy
Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination.
Patients with previously untreated AML or high risk myelodysplastic syndrome (MDS) (>= 10 % blasts or International Prognostic Scoring System [IPSS] >= intermediate-2); prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, all-trans retinoic acid (ATRA), or an isolated dose of cytarabine up to 2 g is allowed; patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML
Patients with active AML or MDS at the time of the study (anything less than a complete remission) are not eligible for this protocol
Subjects with evidence of relapsed or refractory acute myeloid leukemia (AML) OR treatment naive AML who are 75 years or older OR relapsed or refractory myelodysplastic syndrome (MDS)\r\n* For subjects with relapsed AML: evidence of >= 5% blasts in the bone marrow; or reappearance of blasts in the peripheral blood; or development of extramedullary disease (according to 2003 IWG criteria) who relapse after:\r\n** Allogeneic hematopoietic stem cell transplant, or\r\n** After one cycle of standard cytotoxic chemotherapy or two cycles of any hypomethylating agent-based therapy\r\n* For subjects with refractory AML: =< 2 prior induction regimens (example: patients who receive 7+3 followed by 5+2 would count as one induction regimen) or a minimum of two cycles of any hypomethylating agent-based therapy\r\n* For subjects with treatment-naive AML: must be 75 years and older with de novo or secondary AML to be considered eligible\r\n* For subjects with relapsed MDS: disease recurrence after CR, partial remission (PR) or hematologic improvement with bone marrow blasts >= 5% who relapse after:\r\n** Allogeneic hematopoietic stem cell transplant, or\r\n** After four cycles of any hypomethylating agent-based therapy\r\n* For subjects with refractory MDS: disease progression at any time after initiation of hypomethylating agent treatment or persistent bone marrow blasts >= 5% despite a minimum of four cycles of hypomethylating agent therapy
Having received more than one induction systemic therapy for AML or having received a standard dose or high dose ara-C containing regimen for MDS
Patients diagnosed with AML or MDS per below:
Confirmed diagnosis of refractory/relapsed AML or high-risk MDS
Meets one of the following disease criteria:\r\n* Primary (de novo) AML or higher-risk MDS with induction failure: No complete remission (CR) after 2 or more induction attempts with high dose chemotherapy or hypomethylating agents +/- other agents. Higher risk MDS defined as risk score > 4.5 based on the revised International Prognostic Scoring System (IPSS) criteria\r\n* Secondary AML (from antecedent hematologic malignancy or treatment-related): Not in CR after 1 or more cycles of chemotherapy\r\n* Relapsed AML: Blast count >= 5% in bone marrow or peripheral blood after prior attainment of CR; relapse at any time but >= 100 days following allogeneic hematopoietic cell transplantation (HCT)\r\n* Relapsed MDS: Morphologic evidence of relapse or increase in blasts >= 5% in bone marrow or peripheral blood after prior attainment of CR; relapse at any time but ?100 days following allogeneic HCT
Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted but not with hypomethylating agents.
Patients with secondary AML are eligible for enrollment onto the trial; secondary AML is defined as AML that has developed in a person with a history of antecedent blood count abnormalities, or myelodysplastic syndrome (MDS), or a myeloproliferative disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or radiation therapy for a disease other than AML\r\n* NOTE: Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine is excluded
TREATMENT: Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS), or with features suggestive of AML/MDS, or who have had prior allogeneic bone marrow transplant or double umbilical cord blood transplantation, should not receive veliparib due to reports of MDS and leukemia secondary to oncology therapy on Cancer Therapy Evaluation Program (CTEP)-sponsored studies utilizing veliparib
Patients with AML, relapsed or refractory to standard therapy or elderly patients with AML (age 65 or over). Patients who have AML and are younger than age 65 but considered unfit for conventional chemotherapy are eligible. Patients with de novo or treated MDS or chronic myelomonocytic leukemia (CMML) INT-1 or above are eligible. Patients may have had prior exposure to azacitidine but no more than one cycle of decitabine. Patients must have been off chemotherapy for 2 weeks prior to entering this study and have recovered from the toxicities of that therapy; a caveat to this is in the case of rapidly progressive disease. Hydroxyurea is permitted for control of elevated white blood cell (WBC) prior to treatment and can be continued for the first 4 weeks of therapy. Erythropoiesis stimulating agents (ESAs) and granulocyte colony stimulating factor (GCSF) are allowed before therapy. ESAs, GCSF or other growth factors are permitted on therapy.
Patients with MDS that has evolved to AML must be in remission
Patients with AML or MDS arising from myeloproliferative neoplasm can be enrolled after principal investigator (PI) approval on case to case basis, depends on the spleen size and degree of bone marrow fibrosis
Patients with MDS evolved into AML that is not in remission
Subject has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
Subjects with AML evolving from MDS may have received prior MDS therapy with demethylating agents
AML secondary to prior MDS, or
For patients registered to the relapsed/refractory cohort (Cohort 2), patients must have a previous morphologically confirmed diagnosis of acute myeloid leukemia (AML)\r\n* For patients registered to the myelodysplastic syndromes (MDS) transformed to AML cohort (Cohort 1), patients must have a previous morphologically confirmed diagnosis of MDS/chronic myelomonocytic leukemia (CMML); patients may have received previous non-intensive therapy (e.g. azacitidine, decitabine, low-dose cytarabine [LDAC], lenalidomide) given for treatment of MDS/CMML (with up to 20% blasts); at the time of registration they must have a morphologically confirmed diagnosis of AML\r\n* Note: This protocol uses the World Health Organization (WHO) diagnostic criteria for AML; patients with acute promyelocytic leukemia (APL, French American British [FAB], M3) or blastic transformation of chronic myelogenous leukemia are not eligible
Patients with prior malignancy (other than AML and MDS/CMML) are eligible; however, the patient must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy at least 6 months prior to registration; except for AML and MDS treatment, all treatment related toxicities must have been resolved; NOTE: for patients with prior history of malignancy who have received anthracyclines or mediastinal/pericardial radiation in the past, the risk versus benefit of therapy should be weighed, particularly in the setting of receiving consolidation therapy
Diagnosis of MDS, CMML, or RAEB-t/non-proliferative AML (as defined by 20-30% BMBL, WBC ? 25,000 x 10^9/L and stable for at least 4 weeks without intervention) according to World Health Organization (WHO) criteria or French American British (FAB) classification either previously treated or previously untreated. The diagnosis must be confirmed via BM aspirate and/or biopsy within 6 weeks prior to Screening. Note: patients with RAEB-t/non-proliferative AML (as defined by 20-30% BMBL, WBC ? 25,000 x 10^9/L and stable for at least 4 weeks without intervention) are not eligible for the Phase II Part 1 RPTD component of the study and patients with CMML will not be eligible for Phase II Part 2 Expansion of the study.
Off all other treatments for MDS, CMML, or AML including an erythropoiesis-stimulating agent (ESA), for at least 4 weeks prior to Screening. Filgrastim (G-CSF) is allowed before and during the study, as clinically indicated.
Anemia due to factors other than MDS, CMML, or AML (including hemolysis or gastrointestinal bleeding).
Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated.
Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
Patients who have received prior induction chemotherapy for AML or myelodysplastic syndrome (MDS); temporary prior measures such as apheresis or hydroxyurea are allowed; patients who have received a limited and short-term exposure of ATRA (all trans retinoic acid) while AML-M3 (acute promyelocytic leukemia) was being ruled out, and which has been discontinued, will be eligible
Participants with MDS, CMML, or low blast AML, whose only site of disease is extramedullary, example, the skin.
Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML
Patients with secondary AML or therapy related disease (t-AML) are eligible; patients who received decitabine or 5-azacytidine as prior treatment for myelodysplastic syndrome (MDS) remain eligible
Pathological diagnosis of AML according to World Health Organization (WHO) criteria (with at least 20% blasts in the peripheral blood or bone marrow): newly diagnosed de novo AML; except for acute promyelocytic leukemia (APL); newly diagnosed secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease [MPD] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de novo AML with MDS-associated karyotype
To be considered at high risk for induction mortality patients must have 1 or 2 of the following risk factors (patients >= 60 must have at least 1 risk factor, patients < 60 must have at least 2 risk factors) present; at least one risk factor in every patient must be an AML-related factor: \r\n* AML-related factors include: \r\n** Antecedent hematologic disorder (AHD) (MDS, chronic myelomonocytic leukemia [CMML], or MPD) or history of exposure to cytotoxic chemotherapy [therapy-related (t)-AML]), or WHO-defined AML with MDS-related changes or apparent de novo AML with MDS-associated karyotype\r\n** Unfavorable cytogenetics as defined by the European Leukemia Net\r\n* Patient-related factors:\r\n** Age >= 70\r\n** ECOG performance status (PS) >= 2\r\n* Co-morbidities:\r\n** Serum creatinine > 1.3 g/dL
Patients with untreated acute myeloid leukemia (AML) (> or equal to 20% blasts in bone marrow and/or peripheral blood) or high risk MDS (> or equal to 10% blasts in bone marrow); A. patients with AML and history of MDS who have received prior therapy with a hypomethylating agent (including azacytidine) and/or with lenalidomide for prior MDS are eligible if the treating physician feels that participation in the study is in the patients' best interest; B. patients should have molecular evidence of the presence of FLT3-ITD mutation with a molecular burden of at least 10%
For patients with newly diagnosed disease: diagnosis of “high-risk” myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; for patients with relapsed/refractory disease: prior diagnosis of “high-risk” MDS or non-APL AML, with relapsed/refractory disease according to standard criteria requiring first or subsequent salvage therapy; patients with biphenotypic AML are eligible
Diagnosis of AML (AML de novo and post-MDS) or DLBCL
AML participants ? 60 years old in first relapse with a disease-free interval < 12 months, or further relapse. First relapse is also applicable to AML post-MDS patients who have received prior treatment for MDS, but have not received prior treatment for AML.
Patients with one of the following diagnoses:\r\n* Intermediate, high and very high risk (per International Prognostic Scoring System [IPSS]-revised [R]) untreated MDS or any MDS with >= 5% marrow blasts (by French American British [FAB] and World Health Organization [WHO] diagnostic criteria); NOTE: MDS/MPN overlap is allowed\r\n* CMML requiring treatment per doctor of medicine (MD) judgment\r\n* Low and very low risk MDS patients symptomatic and/or transfusion dependent, (>= 4 U red blood cells [RBC] over the preceding 12 week period) who have failed erythropoietin-stimulating agents (ESAs) or who have a low likelihood of responding to ESAs\r\n* MDS and CMML patients relapsed/refractory to hypomethylating agents as evidenced by one of the following:\r\n** Progressed at any time during treatment with hypomethylating agents\r\n** Failed to achieve a response after 6 cycles of 5-azacytidine or 4 cycles of decitabine\r\n** Progressed after treatment with hypomethylating agents had been discontinued\r\n*** NOTE: MDS/MPN overlap is allowed\r\n* Relapsed or refractory AML exposed to =< 3 prior regimens (note, induction and consolidation including stem cell transplantation count as one regimen)\r\n* For exploratory phase I LDE225 days 1-7 with azacitidine or LDE225 days 1-28 with decitabine cohorts only: untreated AML/CMML/MDS/MPN overlap or relapsed/refractory AML/CMML/MDS/MPN overlap WITHOUT prior exposure to a hypomethylating agent (HMA)\r\n* Elderly (age >= 60) untreated AML and not a candidate for induction therapy\r\n* Untreated AML < 60 year of age who are not candidates to undergo standard induction chemotherapy\r\n* Primary myelofibrosis (PMF) and post essential thrombocytopenia (ET)/polycythemia vera (PV) MF with a Dynamic International Prognostic Scoring System (DIPSS)-plus score of intermediate or high, or a > 10% blasts in the marrow and who are in need of therapy and who have failed previous treatment with a janus kinase 2 (JAK2) inhibitor and, if appropriate, have failed Interferon based treatment
Pathological diagnosis of AML (by World Health Organization [WHO] criteria) or higher risk MDS (includes intermediate [int]-2 and high risk MDS by International Prognostic Scoring System (IPSS) along with one of the following:\r\n* Patients with de novo or secondary MDS with progression/refractoriness after HMA treatment who have not transformed to AML\r\n* Patients with MDS and prior HMA treatment for MDS who transformed to AML \r\n* Patients with AML who are refractory/relapsed after HMA therapy for their AML are eligible
Subjects with a histologically confirmed diagnosis of MDS by FAB criteria, including both MDS and RAEB-T (AML with 20-30% blasts and multilineage dysplasia) by World Health Organization (WHO) classification are eligible.
Previously untreated AML (>= 20% blasts); patients with high-risk MDS (defined as having >= 10% blasts in the bone marrow) or patients with chronic myelomonocytic leukemia (CMML) (having >= 10% blasts in the bone marrow) may also be eligible after discussion with principal investigator (PI); prior therapy with hydroxyurea, biological or targeted therapy (e.g. fms-related tyrosine kinase 3 [FLT3] inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however prior therapy with chemotherapy agents for the disease under study is not allowed; patients may have received one dose of cytarabine (up to 2 g/m^2) administered at presentation for control of hyperleukocytosis; for patients with prior MDS or CMML who transformed to AML, therapy received for MDS is not considered as prior therapy for AML
Prior or concomitant chemotherapy for AML (with the exception of hydroxyurea and/or corticosteroid therapy for no more than 28 days (cumulative)). Please note that any prior therapy for MDS is allowed.
Patients must meet one of two disease criteria:\r\n* Acute myelogenous leukemia within one of the following categories:\r\n** Primary induction failure (PIF): patients who have not achieved a complete remission following initial diagnosis and after at least two induction cycles of chemotherapy consisting of cytarabine and an anthracycline or high-dose cytarabine\r\n** Relapsed AML: Patients are defined as having relapsed disease if they entered a complete remission confirmed with a bone marrow biopsy following initial treatment, and then were found to have morphological or cytogenetic evidence of recurrent disease on a subsequent bone marrow exam\r\n** Any complete remission (CR)2 or greater: CR must be defined using a bone marrow exam taken at least 21 days since the last chemotherapy (including a methyltransferase inhibitor), and may include CRp (morphologic CR without peripheral platelet recovery)\r\n** CR1 with high-risk features: includes patients with treatment-related AML, secondary AML (following myelodysplastic syndrome [MDS] or myeloproliferative neoplasms [MPN]), high-risk cytogenetic or molecular phenotype (by National Comprehensive Cancer Network [NCCN] criteria)\r\n** Untreated AML (> 20% blasts on a bone marrow) arising from a previous confirmed diagnosis of MDS or MPN (excluding breakpoint cluster region [BCR]-Abelson murine leukemia viral oncogene homolog 1 [ABL] positive disease)\r\n* Myelodysplastic syndromes within one of the following categories:\r\n** High-risk MDS at diagnosis as defined by the International Prognostic Scoring System (IPSS) or World Health Organization (WHO) classification based Prognostic Scoring System (WPSS)\r\n** Transfusion dependent MDS (either red blood cells [RBC] or platelet dependent) without a hematologic response to at least 4 months of MTI therapy; hematological response is defined as transfusion independence for two or more months\r\n** Progressive MDS following at least 4 months of MTI therapy; progression is defined as resumption of transfusion dependence after at least two months of transfusion independence OR increase of marrow blasts by 50% from pretreatment OR overall blasts over 10% of marrow cells at any time after treatment
AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS
Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.
Patient must have non-M3 AML or MDS
Patients with antecedent MDS/MPN, defined by WHO criteria, without any prior therapy for AML, regardless of the number of therapies for MDS/ MPN
For the phase I portion of the study patients should have failed any number of prior therapies, which should include at least the following: 1. Patients with MDS should have failed prior therapy with a hypomethylating agent and/or with lenalidomide. 2. Patients with AML should have failed any prior induction therapy or have relapsed after prior therapy. 3. Patients with MDS who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless of any prior therapy for AML. 4. Patients with any of the eligible diagnoses who have received no prior therapy are eligible if not candidates to receive standard therapy or if they refuse standard chemotherapy.
For the phase II Portion of the study, only patients who are previously untreated for AML. 1. Patients with history of MDS who received therapy for MDS and progressed to AML are eligible at the time of diagnosis of AML. Only induction chemotherapy administered for AML will be considered for considerations of eligibility regarding prior therapy. Patients who received therapy for MDS before transforming to AML (e.g., with hypomethylating agents or lenalidomide) are eligible.
Isolated myeloid sarcoma not meeting bone marrow criteria for AML or MDS
Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:\r\n* AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)\r\n* AML or ALL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens)\r\n* AML evolved from myelodysplastic or myeloproliferative syndromes; or \r\n* MDS expressed as refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria
Key Inclusion Criteria (Phase 1):\n\n        - Confirmed hematologic malignancy, including Acute Myeloid Leukemia (AML), Chronic\n        Lymphocytic Leukemia (CLL), Chronic Myelogenous Leukemia (CML), Acute Lymphocytic Leukemia\n        (ALL), Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM), Myelofibrosis (MF),\n        Myeloproliferative Neoplasms (MPN) or MDS/MPN overlap diseases. (Once Phase 2 has started\n        subjects with AML will be eligible for inclusion in the Phase 1 portion of the study only\n        if their malignancy has been shown to have c-Cbl mutation, trisomy 3, trisomy 11, inv(16),\n        or elevated FLT3. [Other AML and subjects with MDS will no longer be eligible for\n        inclusion in the Phase 1 portion of the study]).\n\n        Key Inclusion Criteria (Phase 2):\n\n          -  Part A: AML or MDS patients with an acceptable level of EphA3 expression\n\n          -  Part B: MF patients with an acceptable level of EphA3 expression\n\n        Key Inclusion Criteria (Both Phases):\n\n          -  Confirmed hematologic malignancy refractory to or progressed following standard\n             treatments, or subjects not considered medically suitable to receive standard of care\n             treatment or who refuse standard of care treatment\n\n          -  Acceptable level of EphA3 expression\n\n          -  Eastern Cooperative Oncology Group (ECOG) ?1\n\n          -  Acceptable laboratory results\n\n        Key Exclusion Criteria (Both Phases):\n\n          -  For subjects with AML, more than 2 prior therapies for AML (induction and\n             consolidation with or without a hypomethylating agent given in a maintenance setting\n             are considered 1 therapy)\n\n          -  History of or current central nervous system (CNS) involvement that may increase risk\n             of bleeding\n\n          -  Recent major surgery\n\n          -  Ongoing surgical or wound healing complications\n\n          -  Active clinically significant bleeding\n\n          -  Uncontrolled hypertension\n\n          -  Significant intercurrent illness\n\n          -  Known history of prolonged bleeding times or platelet dysfunction\n\n          -  Active infection requiring IV antibiotics, IV antifungals, or IV antivirals within 2\n             weeks prior to Cycle 1, Day 1
Key Inclusion Criteria (Phase 1):\n\n        - Confirmed hematologic malignancy, including Acute Myeloid Leukemia (AML), Chronic\n        Lymphocytic Leukemia (CLL), Chronic Myelogenous Leukemia (CML), Acute Lymphocytic Leukemia\n        (ALL), Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM), Myelofibrosis (MF),\n        Myeloproliferative Neoplasms (MPN) or MDS/MPN overlap diseases. (Once Phase 2 has started\n        subjects with AML will be eligible for inclusion in the Phase 1 portion of the study only\n        if their malignancy has been shown to have c-Cbl mutation, trisomy 3, trisomy 11, inv(16),\n        or elevated FLT3. [Other AML and subjects with MDS will no longer be eligible for\n        inclusion in the Phase 1 portion of the study]).\n\n        Key Inclusion Criteria (Phase 2):\n\n          -  Part A: AML or MDS patients with an acceptable level of EphA3 expression\n\n          -  Part B: MF patients with an acceptable level of EphA3 expression\n\n        Key Inclusion Criteria (Both Phases):\n\n          -  Confirmed hematologic malignancy refractory to or progressed following standard\n             treatments, or subjects not considered medically suitable to receive standard of care\n             treatment or who refuse standard of care treatment\n\n          -  Acceptable level of EphA3 expression\n\n          -  Eastern Cooperative Oncology Group (ECOG) ?1\n\n          -  Acceptable laboratory results\n\n        Key Exclusion Criteria (Both Phases):\n\n          -  For subjects with AML, more than 2 prior therapies for AML (induction and\n             consolidation with or without a hypomethylating agent given in a maintenance setting\n             are considered 1 therapy)\n\n          -  History of or current central nervous system (CNS) involvement that may increase risk\n             of bleeding\n\n          -  Recent major surgery\n\n          -  Ongoing surgical or wound healing complications\n\n          -  Active clinically significant bleeding\n\n          -  Uncontrolled hypertension\n\n          -  Significant intercurrent illness\n\n          -  Known history of prolonged bleeding times or platelet dysfunction\n\n          -  Active infection requiring IV antibiotics, IV antifungals, or IV antivirals within 2\n             weeks prior to Cycle 1, Day 1
Subjects with MDS/AML or with features suggestive of MDS/AML;
Patients with a diagnosis of acute myeloid leukemia (AML) (World Health Organization classification: >= 20% blasts in the bone marrow and/or peripheral blood) or myelodysplastic syndrome (MDS) (International Prognostic Scoring System intermediate-1 or higher) that at the time of allogeneic transplantation were in: - induction failure, relapsed disease or second or greater remission; patients in first complete remission that required more than 1 cycle of treatment to achieve the remission, or that have AML evolving from MDS, or that had the following abnormalities: FLT3 mutation, deletion of chromosome 5 or 7, mixed-lineage leukemia (MLL) gene rearrangement, or more than or equal to 3 cytogenetics abnormalities; patients with de novo or therapy-related MDS, chronic myelomonocytic leukemia (CMML) or AML are also eligible, regardless of cytogenetics or molecular rearrangements
Patients with AML, MDS, ALL, or CML must not have presence of circulating leukemic blasts detected by standard pathology
Patients must be in a documented CR/CRi from either their front-line or first salvage therapy as evidenced by =< 5% bone marrow blasts and absence of extramedullary disease; (for patients with prior MDS who then transformed to AML, therapy received for MDS is not considered prior therapy for AML)
Diagnosis of AML or MDS according to the WHO criteria
Confirmed diagnosis of AML, including treatment-related secondary AML (except prior MDS) according to World Health Organization (WHO) 2008 classification at treating institution
Bone marrow blast < 20% if MDS or ? 10% if AML; and
Diagnosis of untreated “high-risk” MDS (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available\r\n* Prior hydroxyurea for AML is permitted but should be discontinued prior to start of CPX-351 treatment\r\n* Azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk MDS (< 10% blasts); all treatments for MDS should be discontinued prior to start of CPX-351 treatment
Patients must be chemo-naïve, i.e., not have received any prior induction chemotherapy for AML or myelodysplastic syndrome (MDS); temporary prior measures such as apheresis or hydroxyurea are allowed; prior anthracycline therapy is allowed, but must not exceed a dose of 200 mg/m^2 daunorubicin or equivalent; prior all-trans retinoic acid (ATRA) for suspected APL is allowed; prior methotrexate for central nervous system (CNS) involvement is allowed; patients with prior history of MDS must not have received azacitidine, decitabine, lenalidomide or vorinostat
Must have one of the following diagnoses:\r\n* Pathologically confirmed chronic myelomonocytic leukemia (CMML) or myelodysplastic syndromes (MDS) with high risk features at the time of referral for trial as defined by:\r\n** Intermediate (INT)-2 or high International Prognostic Scoring System (IPSS) score\r\n** Secondary MDS (defined as MDS developing in a patient with an antecedent hematologic disorder or any patient with prior chemotherapy or radiation exposure)\r\n** INT-1 MDS with excess blasts (>= 5% blasts in bone marrow [BM]) or red blood cell (RBC) transfusion-dependency\r\n** MDS progressing to oligoblastic acute myeloid leukemia (AML) with 21-30% BM blasts\r\n** CMML with >= 5% marrow blasts, or RBC or platelet transfusion-dependency, abnormal karyotype, or proliferative features (white blood cell count >=13,000/uL, splenomegaly on physical examination, or extramedullary disease)\r\n** All patients are required to have failed to respond or relapsed after an initial response to hypomethylating agents 5-azacitidine or decitabine or have refused to receive hypomethylating therapy; failure to respond is defined as failing to achieve a CR, PR or HI after at least 4 cycles of hypomethylating therapy; these patients could have received other therapies or not, but must have received hypomethylating therapy or have refused to receive hypomethylating therapy\r\n* Pathologically confirmed AML patients who have received one or two courses of induction chemotherapy or hypomethylating agent therapy AND no plans for further chemotherapy therapy, but remain with residual disease of < 5% blasts in BM, by morphology, cytogenetics, fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR) or flow cytometry
Prior diagnosis of “high-risk” myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17) (q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible
May have previously received monotherapy with demethylating agents for MDS or AML
May have previously received chemotherapy with MEC for MDS or AML
Patients with secondary MDS/AML
Known history of MDS or AML Cohort 3 Exclusion Criteria:
Known history of MDS or AML
Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease or high-risk features defined as: \r\n* Greater than 1 cycle of induction therapy required to achieve remission\r\n* Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease\r\n* Presence of fms-related tyrosine kinase 3 (FLT3) mutations or internal tandem duplications\r\n* French-American-British (FAB) M6 or M7 classification\r\n* Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 (> 3 abnormalities), peripheral blood blasts < 1000/microliter, AML patients must show response to most recent received chemotherapy
Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)\r\n * Patients with AML will be eligible in first relapse or 2nd or 3rd complete remission; patients not in remission must have < 25% blasts in the bone marrow prior to admission to the hematopoietic stem cell transplant (HSCT) unit; patients with MDS will be eligible if no other suitable donor can be identified\r\n * In general, patients will be preferentially transplanted using a matched unrelated donor or umbilical cord blood; AML/MDS patients will be eligible for this study if a suitable related or unrelated donor cannot be identified, the amount of time required to identify a suitable donor is deemed unacceptable, or the patient is not eligible for a myeloablative transplant regimen\r\n * Patients who relapse following a myeloablative transplant, but cannot receive DLI (e.g. cord blood recipients, graft loss) will also be eligible; such patients must be >= 6 months post initial transplant, achieve a CR or have < 25% blasts in the bone marrow prior to admission to the HSCT unit
Patients should have a diagnosis of AML (de novo or transformed from hematologic malignancies), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with one of the following features: (A) patients with MDS or CMML should have failed prior therapy with a hypomethylating agent and/or with lenalidomide (cohorts 2 and 3); (B) patients with AML should have failed any prior therapy or have relapsed after prior therapy (cohorts 2 and 3); for patients in cohort 3 prior therapy should have included a FLT3 inhibitor; (C) patients with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML; these patients will be assigned to cohort 1; patients with MDS, CMML or AML who have received no prior therapy are eligible if age 65 and greater or if, at the time of enrollment, are not candidates to receive or refuse standard therapy (cohort 1 only)
Patients may have had prior treatment for myelodysplastic syndrome (MDS) or AML, including prior lenalidomide for MDS or AML or another condition
Phase I (completed): Participants must have a diagnosis of AML, MDS, ALL or MPAL and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)\r\n* Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy\r\n* Patients with AML, MPAL or MDS are eligible at first or subsequent relapse, whereas patients with ALL are eligible at second or subsequent relapse or any relapse that is refractory to salvage chemotherapy\r\n* Patients with AML or ALL must have >= 5% leukemic blasts in the bone marrow or increasing levels of MRD in the bone marrow as assessed by flow cytometry; if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood
Patients with AML or high-risk MDS receiving non-intensive therapy including hypomethylating agents, single-agent chemotherapy, targeted therapy agents, single or combination non-intensive agents offered on a clinical trial, or any other chemotherapy offered for patients with AML and high-risk MDS that does not require a prolonged 4-6 week hospitalization including the following populations:\r\n* Newly diagnosed AML\r\n* Relapsed or primary refractory AML\r\n* Newly diagnosed high-risk MDS\r\n* Relapsed or primary refractory high-risk MDS
Patients with secondary AML arising out of myelodysplastic syndrome (MDS) (all subtypes under WHO classification), chronic myelomonocytic leukemia (CMML); therapy-related AML and those with a prior autologous hematopoietic cell transplantation are eligible
Secondary AML arising out of myeloproliferative neoplasms (as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias) and MDS/myeloproliferative (MPD) neoplasms other than CMML (as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias); refractory anemia with ringed sideroblasts with thrombocytosis (RARS-T) classified as MDS/myeloproliferative neoplasm (MPN) neoplasm, unclassifiable will be excluded; AML patients with presenting features suspicious of underlying unrecognized MPD such as marked splenomegaly (>= 20 cm) and or thrombocytosis (> 400,000 per microliter) will be excluded; patients with relapsed or refractory AML will be excluded
Untreated AML, including patients with an antecedent hematologic disorder or secondary disease. Patients with prior MDS may have received therapy with immunomodulatory agents or hypomethylating agents for this diagnosis. Patients with other prior cancer diagnoses are allowed as long as they have no measurable disease, are not undergoing active therapy, and have a life expectancy of ? 4 months.
Untreated AML, including patients with an antecedent hematologic disorder or secondary disease. Patients with prior MDS may have received therapy with immunomodulatory agents for this diagnosis.
Patients with either newly diagnosed AML or MDS who have either begun (within 4 days of starting study drug) or are planned to begin specific treatment for their AML/MDS; patients who are participating in other therapeutic clinical trials for their AML/MDS may participate in this trial
CD123/IL3RA expression on the subject’s AML or MDS blasts, determined locally within 3 months of first protocol treatment
With relapsed or refractory AML (hydroxyurea is not considered a prior treatment regimen) OR with treatment-naive AML who decline intensive induction chemotherapy or who are unfit due to co-morbidity or other factors OR with MDS and >= 10% myeloblasts in the bone marrow
Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS, MDS/MPN, CMML or AML within 14 days of the first day of study drug treatment
In the Dose Expansion Segment, hypomethylating agent (HMA) treatment-naïve MDS subjects (including CMML), and intermediate-2 or high-risk MDS subjects (including CMML) relapsed or refractory to prior HMA treatment are allowed, and treatment-naïve AML subjects who are at least 65 years of age will be allowed if they also have at least one of the following criteria
AML secondary to MDS, chemotherapy, or radiation therapy
Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS), or with features suggestive of AML/MDS, or who have had prior allogeneic bone marrow transplant or double umbilical cord blood transplantation, should not receive veliparib due to reports of MDS and leukemia secondary to oncology therapy on Cancer Therapy Evaluation Program (CTEP)-sponsored studies utilizing veliparib
REGISTRATION STEP 2-RANDOMIZATION: Patients must have morphologically confirmed, previously untreated acute myeloid leukemia (AML) or MDS with excess blasts-2 (MDS-EB-2)\r\n* Patients with acute promyelocytic leukemia (APL), biphenotypic leukemia, blastic transformation of chronic myelogenous leukemia (CML or BCR/ABL), are not eligible\r\n* Patients must have disease present in the blood or bone marrow; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible\r\n* All tests for establishing baseline disease status eligibility must be based on blood and/or bone marrow examination performed within 42 days prior to randomization (registration Step 2)
Patients with acute bilineal/biphenotypic leukemia
leukemia in 2nd or higher relapse,
Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt’s leukemia based on World Health Organization (WHO) classification; patients with bilineal leukemia are excluded
Acute lymphocytic leukemia (ALL): must have < 5% marrow blasts at the time of transplant
Diagnosis of acute promyelocytc leukemia
Have current acute leukemia.
Diagnosis of acute leukemia or any patient that has been treated with fludarabine.
T-cell prolymphocytic leukemia
Prior history of acute leukemia or AML
NK cell leukemia.
Any acute leukemia with marrow aplasia or without adequate count recovery.
Mixed phenotype acute leukemia MRD > 1% after consolidation
Participants must have a diagnosis of AML or acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia) and meet the criteria below:\r\n* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy, OR\r\n* Early relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission and within one year of diagnosis, OR\r\n* Relapsed leukemia that is refractory to at least one course of salvage therapy (i.e., therapy given after the relapse has occurred), OR\r\n* Second or greater relapse\r\nPatients in all categories above must have >= 5% blasts in the bone marrow as assessed by morphology or flow cytometry; however, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with >= 5% blasts in the peripheral blood; in addition, patients in all categories must not be eligible to undergo curative therapy, such as immediate stem cell transplantation (SCT)
Diagnosis of acute leukemia
Patient has newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia with >= 25% blasts in the bone marrow (M3), with or without extramedullary disease; patients with T-cell ALL are eligible; patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominantly lymphoid
leukemia
Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:\r\n* Acute lymphocytic leukemia in first or subsequent remission\r\n* Acute myeloid leukemia in first or subsequent remission \r\n* Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)\r\n* Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)\r\n* Refractory anemia with excess blasts (RAEB-1 and RAEB-2) (if the patient has received previous induction chemotherapy within 60 days)\r\n* Chronic myelogenous leukemia with a history of accelerated phase or blast crisis (if the patient has received at least one course of induction chemotherapy)\r\n* Other acute leukemia or related neoplasm (including but not limited to ‘biphenotypic’, ‘undifferentiated’ or ‘ambiguous lineage’ acute leukemia, blastic plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma)
Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:\r\n* All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age; patients who do not have high-risk features (for example preceding myelodysplastic syndrome [MDS], high-risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia or >= CR2) must be discussed with the principal investigator (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 PI prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
Acute lymphocytic leukemia (ALL) – must have < 5% marrow blasts at the time of transplant
Refractory acute leukemia (> 5% blasts) or progressive disease
Have acute leukemia.
Acute biphenotypic or bilineal leukemia in first or greater complete remission
Diagnosis of acute leukemia by World Health Organization (WHO) criteria (e.g.-acute myeloid leukemia, acute lymphoblastic leukemia, acute leukemia of ambiguous origin)
Histologically confirmed diagnosis of relapsed or refractory acute lymphoblastic leukemia (ALL) (including Burkitt leukemia), acute myeloid leukemia (AML), mixed lineage leukemia, biphenotypic leukemia, or chronic myelogenous leukemia (CML) in blast crisis\r\n* Refractory disease defined as: persistent disease after at least two induction cycles\r\n* Relapsed disease: second or subsequent relapse, any relapse refractory to salvage chemotherapy
Acute leukemia not in remission
Newly diagnosed or relapsed mixed phenotype acute leukemia (MPAL), which for this protocol, will be defined as follows: bone marrow result interpreted by the reading pathologist (or tissue biopsy for cases of extramedullary disease) as: biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population
Patients with biopsy-proven acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome in remission or relapse
Relapsed or refractory acute leukemia (acute myeloid leukemia or acute lymphoblastic leukemia or lymphoma) in second or subsequent remission, with remission defined as < 5% bone marrow blasts morphologically
Acute myeloid leukemia/acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia: Must have < 5% morphologic marrow blasts in an evaluable marrow sample (> 25% of normal cellularity for age collected less than one month prior to start of conditioning; 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 persistently aplastic for greater than one month since completing last chemotherapy are also eligible with principal investigator (PI) approval
Acute myeloid leukemia/acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia: Must have < 5% morphologic marrow blasts in an evaluable marrow (> 25% of normal cellularity for age) collected less than one month prior to start of conditioning; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with the approval of the PI or designee
Diagnosis of acute lymphoblastic leukemia (ALL) or biphenotypic leukemia meeting the following criteria:
Based on European Group for the Classification of Acute Leukemia (EGIL) diagnostic criteria
Must not have acute leukemia
Diagnosis of refractory or relapsed ALL (acute lymphocytic leukemia)
Malignancies included are:\r\n* Acute leukemia, including Acute myeloid leukemia (AML), biphenotypic acute leukemia or mixed-lineage leukemia, acute lymphoblastic leukemia (ALL); all patients must be in complete response (CR) as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with adequate cellularity to assess remission status\r\n* Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology\r\n* Chronic Myeloid Leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy
Patients with a diagnosis of relapsed or refractory hematologic malignancy including, but not limited to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), Burkitt’s leukemia/lymphoma, prolymphocytic leukemia, biphenotypic acute leukemia, blast-phase of chronic myeloid leukemia (CML), B-cell lymphoma, or Richter’s transformation of chronic lymphocytic leukemia (CLL)
Participants whose leukemia meets WHO diagnostic criteria of mixed phenotype acute leukemia (MPAL) or leukemia of ambiguous lineage are not eligible
Bi-phenotypic acute leukemia
Acute leukemia of ambiguous lineage (biphenotypic leukemia)
Patients with any of the following oncologic diagnoses are not eligible:\r\n* Any concurrent malignancy\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Philadelphia chromosome positive AML\r\n* Biphenotypic or bilineal acute leukemia\r\n* Acute promyelocytic leukemia\r\n* Acute myeloid leukemia arising from myelodysplasia\r\n* Therapy-related myeloid neoplasms\r\nNote: enrollment may occur pending results of clinically indicated studies to exclude these conditions
Patients with one of the following diagnoses:\r\n* Acute myeloid leukemia (AML)\r\n* Acute lymphoblastic leukemia (ALL)\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Myelodysplastic syndrome (MDS)
Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:\r\n* Acute lymphocytic leukemia in first or subsequent remission\r\n* Acute myeloid leukemia in first or subsequent remission \r\n* Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3\r\n* Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 \r\n* Refractory anemia with excess blasts (RAEB-1 and RAEB-2) \r\n* Chronic myelogenous leukemia with a history of accelerated phase or blast crisis\r\n* Other acute leukemia (including but not limited to ‘biphenotypic’, ‘undifferentiated’ or ‘ambiguous lineage’ acute leukemia)
AML or acute leukemia of ambiguous lineage:\r\n* If relapse AML or acute leukemia of ambiguous lineage:\r\n** Must have a prior diagnosis of AML or acute leukemia of ambiguous lineage and be in 1st or greater relapse as evidenced by morphology, immunophenotype, molecular or cytogenetic signature\r\n** Must not have received prior reinduction therapy for this relapse\r\n* If primary refractory AML or acute leukemia of ambiguous lineage:\r\n** Must have had a prior diagnosis of AML or acute leukemia of ambiguous lineage and\r\n** Must not have received more than 3 previous induction attempts\r\n* If primary AML or acute leukemia of ambiguous lineage newly diagnosed or in remission\r\n** Primary treating oncologist must have deemed patient unable to complete standard treatment therapy and selected FLAG as appropriate alternative regimen\r\n* If prior diagnosis of acute lymphoblastic leukemia must have evidence of transformation to AML or acute leukemia of ambiguous lineage as evidenced by morphology, immunophenotype, molecular or cytogenetic signature\r\n* Patients meeting above criteria are eligible regardless of central nervous system (CNS) classification
Disease associated with secondary MF such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease or acute leukemia (including M7 disease or acute panmyelosis with MF)
Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia\r\n* All patients must have acute myeloid leukemia (AML) that is considered best treated by stem cell transplant by the referring physician and the attending transplant physician\r\n* All patients must be in complete remission (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
Acute myelogenous leukemia diagnosed by World Health Organization (WHO) criteria with one of the following:\r\n* Primary refractory disease following >= 1 cycle of induction chemotherapy\r\n* First relapse or higher; patients with primary or secondary acute myelogenous leukemia are eligible; patients with biphenotypic leukemia are eligible
FAB subtype M0 (minimally differentiated acute myeloblastic leukemia), M6 (acute erythroid leukemias, including erythroleukemia (M6a) and pure erythroid leukemia (M6b)), or M7 (acute megakaryoblastic leukemia)
Have an acute leukemia
Bi-phenotypic acute leukemia
Biphenotypic leukemia
Biphenotypic leukemia
Acute lymphocytic leukemia (ALL) must have < 5% marrow blasts at the time of HCT
Recipients with primary or secondary acute leukemia, refractory anemia with excess blasts (RAEB), CML, or other eligible diagnosis in transformation to acute leukemia must have =< 5% blasts in bone marrow and no circulating blasts in peripheral blood at study entry; recipients who do not meet these criteria may be re-evaluated for study eligibility after receiving standard induction therapy for acute leukemia and determined to be in remission
Burkitt’s or mixed lineage leukemia, T cell ALL
Prior morphological diagnosis of AML other than acute promyelocytic leukemia according to the 2001 World Health Organization (WHO) diagnostic criteria; patients with biphenotypic, RAS-mutated acute leukemia are also eligible
The patient must have discontinued all previous therapies for acute leukemia for at least 14 days and recovered from the acute non-hematologic side effects of the therapy
T cell prolymphocytic leukemia
Have current acute or chronic leukemia.
Participant with acute leukemia must meet one of the following criteria:\r\n* Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or acute biphenotypic leukemia in 2nd or greater relapse, or\r\n* Refractory ALL, AML, or acute biphenotypic leukemia failing to achieve CR with >= 2 induction or re-induction attempts
Must not have leukemia.
Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, or myeloproliferative neoplasms requiring a matched allogeneic hematopoietic stem cell transplant (HSCT)\r\n* Acute leukemia (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) must be in complete remission defined as: < 5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow > 20% cellular, and peripheral absolute neutrophil count > 1000/uL (platelet recovery is not required)\r\n* Myelodysplasia (MDS) and chronic myeloid leukemia (CML): must have < 5% marrow blasts\r\n* Myeloproliferative neoplasms (MPN): must have < 5% peripheral/marrow blasts
Acute or chronic leukemia.
Have current acute or chronic leukemia
Have a diagnosis of lung cancer (both small cell and non-small cell), central nervous system tumors, acute myeloid leukemia, and acute lymphoblastic leukemia will be excluded
Acute myelogenous leukemia diagnosed by World Health Organization (WHO) criteria with one of the following (patients with biphenotypic leukemia are eligible, provided that the treating physician determines an acute myeloid leukemia (AML) treatment regimen is appropriate)\r\n* Primary refractory disease following >= 1 cycle of induction chemotherapy\r\n* First relapse or higher; patients with primary or secondary acute myelogenous leukemia are eligible
Acute or chronic leukemia diagnosis
Those with acute leukemia must be in remission at the time of transplant
Any patient with non-acute promyelocytic leukemia (APL) acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], biphenotypic leukemia) undergoing curative intent chemotherapy OR any patient undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for a hematologic disorder (including acute leukemia as above, chronic myelogenous leukemia [CML], chronic lymphocytic leukemia [CLL], myelodysplastic syndrome [MDS], primary or secondary myelofibrosis, hypereosinophilic syndromes, plasma cell disorders, B-cell or T-cell lymphoma)
Patients with acute myelogenous leukemia (AML) or relapsed acute lymphoblastic leukemia (ALL) that will receive chemotherapy with/without transplant must have, or be scheduled to have, an external tunneled CVC (Broviacs, Hickmans, tunneled PICCs, etc.) and/or non-tunneled PICC that is expected to remain in place for an additional >= 3 months
Patients with a hematologic malignancy other than aplastic anemia or primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood stem cell graft from an unrelated donor, using fludarabine phosphate (Flu)/busulfan (Bu) conditioning and tacrolimus (Tac)/methotrexate (MTX) GVHD prophylaxis; the following diagnoses are included:\r\n* Acute leukemia - acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or acute biphenotypic leukemia; patients will have documentation of complete remission within 6 weeks prior to their transplant; complete remission is defined as < 5% blasts on a bone marrow biopsy and absence of any known extramedullary disease\r\n* Chronic myelogenous leukemia in any stage, but with documentation of < 5% blasts on a bone marrow biopsy within 6 weeks prior to transplant\r\n* Myelodysplastic syndrome of any subtype, but with documentation of < 5% blasts on a bone marrow biopsy within 6 weeks prior to transplant\r\n* Myeloproliferative disorders other than primary myelofibrosis\r\n* Lymphoma - all types of lymphoma are eligible\r\n* Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (PLL)
Acute leukemia receiving induction chemotherapy
All acute myelogenous leukemia and high-risk myelodysplastic leukemia patients who are admitted to the leukemia service and those who are referred from other services (i.e. pediatrics, medical oncology, etc.) will be eligible for the study
Intensive induction chemotherapy for a new diagnosis of acute myelogenous leukemia, acute lymphocytic leukemia, or myelodysplastic syndrome receiving standard anthracycline based chemotherapy
New diagnosis of de novo ALL, lymphomas (T or B cell), or mixed-phenotype acute leukemia
Diagnosis of acute myeloid leukemia (AML), acute biphenotypic leukemia, or acute lymphoblastic leukemia (ALL); CML transformed to blast crisis is eligible
Acute leukemia (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) must be in complete remission defined as: < 5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow > 20% cellular, and peripheral absolute neutrophil count > 1000/uL (platelet recovery is not required)
Acute lymphocytic leukemia (ALL) – must have < 5% marrow blasts at the time of transplant
Acute undifferentiated leukemia (AUL)
Acute biphenotypic leukemia
COHORT 1: RELAPSED/REFRACTORY LEUKEMIA \r\n* Acute lymphoblastic leukemia, first or greater relapse\r\n* Acute myeloid leukemia, first or greater relapse\r\n* Leukemia refractory to induction chemotherapy\r\n* Other recurrent leukemia\r\n* Myelodysplastic syndrome (MDS), first or greater relapse, or refractory to initial therapy
COHORT 2: NEW DIAGNOSIS\r\n* Acute myeloid leukemia, new diagnosis\r\n* New diagnosis infant mixed-lineage leukemia (MLL)-rearranged acute lymphoblastic leukemia (ALL) or low hypodiploid (< 40 chromosomes) ALL\r\n* Rare leukemia- e.g., juvenile myelomonocytic leukemia (JMML), leukemia of ambiguous lineage\r\n* Secondary leukemia\r\n* Myelodysplastic syndrome (MDS) not eligible for stem cell transplant
Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
Known leukemia or lymphoma
Subjects must have histologically documented acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), chronic myeloid leukemia (CML), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) or multiple myeloma (MM) as follows:\r\n* Acute myeloid leukemia (AML) with one or more of the following criteria:\r\n** Poor risk cytogenetics, including -5, 5q-, -7, 7q-, t(9;22); complex cytogenetics (>= 3 abnormalities); or normal cytogenetics with Fms-like tyrosine kinase 3 (Flt3) internal tandem duplications (ITD), in first or subsequent complete remission (CR)\r\n** Relapsed or primary refractory AML with =< 10% blasts in the peripheral blood\r\n** Subjects in CR1 who required two cycles of induction to achieve remission may be included at the discretion of the treating physician\r\n** Standard risk or intermediate risk cytogenetics in second or subsequent CR (enrolled at the discretion of the treating physician)\r\n* Acute lymphoblastic leukemia (ALL) with one of the following criteria:\r\n** Second or subsequent CR\r\n** Any partial remission (PR) (no circulating blasts)\r\n** High-risk ALL in first CR including (Philadelphia chromosome positive [Ph+], t(4:11)), complex karyotype, hypodiploidy (< 44 chromosomes), positive minimal residual disease (MRD) after induction, and other high risk features in adults per treating physician\r\n* Myelodysplasia, intermediate-2 (score 1.5-2.0) or high risk (score > 2.5) by the International Prognostic Score System\r\n* Myeloproliferative disorders (include chronic myelomonocytic leukemia [CMML], agnogenic myeloid metaplasia [AMM] or idiopathic myelofibrosis, and juvenile myelomonocytic leukemia [JMML]) with excess blasts (> 5%)\r\n* Chronic myeloid leukemia (CML) with one of the following criteria:\r\n** Second or subsequent chronic phase\r\n** Accelerated phase\r\n** Blast crisis\r\n* Non-Hodgkin's lymphoma (NHL) meeting one of the following criteria:\r\n** Relapse after autologous stem cell transplantation with evidence of responsive disease\r\n** Subject with chemosensitive relapse who have no option for autologous stem cell transplantation due to blood or marrow involvement or failure to mobilize autologous stem cells or are not considered eligible for autologous transplant by their treating physician\r\n* Hodgkin’s lymphoma: relapse after autologous hematopoietic cell transplant (HCT), chemorefractory disease\r\n* Multiple myeloma: per National Comprehensive Cancer Network (NCCN) guidelines
The patient must have a disease (listed below) with treatment-responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:\r\n* Acute leukemia – Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL)\r\n* Chronic leukemia – Chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL)\r\n* Myelodysplasia\r\n* Myeloproliferative disorder\r\n* Myelofibrosis\r\n* Lymphoma – Non-Hodgkin lymphoma (NHL) or Hodgkin’s disease\r\n* Plasma cell disorder, including myeloma, Waldenstrom’s macroglobulinemia.
The patient must have a diagnosis of one of the following (one must be yes):\r\n* Bone marrow failure disorders:\r\n** Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):\r\n*** SAA must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG)\r\n*** PNH must have failed treatment or not tolerated treatment with eculizumab or progressed during or after treatment with eculizumab\r\n** Hereditary bone marrow failure disorders include Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, and congenital amegakaryocytic thrombocytopenia\r\n* Other non-malignant hematologic or immunologic disorders that require transplantation:\r\n** Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann’s thrombasthenia)\r\n** Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)\r\n** Congenital primary immunodeficiencies (including but not limited to severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies)\r\n** Hemoglobinopathies (including sickle cell disease and thalassemia)\r\n* Acute leukemias:\r\n** Acute myeloid leukemia (AML) - antecedent myelodysplastic syndrome, secondary\r\nAML, intermediate cytogenetics, high risk cytogenetic abnormalities or normal cytogenetics with high-risk\r\nmolecular mutations (including but not limiting to Flt3-ITD mutation), or other high risk features as per clinical judgment of the study principal investigator (PI) (or in the absence of the study PI, another equally qualified clinician)\r\n** Acute lymphoblastic leukemia (ALL) - B cell or T cell\r\n* Chronic myelocytic leukemia (CML):\r\n** Chronic phase (intolerant or unresponsive to imatinib and/or tyrosine kinase inhibitors)\r\n** Second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation\r\n* Myeloproliferative and myelodysplasia syndromes:\r\n** Myelofibrosis (with/without splenectomy) with intermediate to high risk features\r\n** Advanced polycythemia vera not responding to therapy\r\n** Myelodysplastic syndrome (MDS) with an Revised International Prognostic Scoring System (IPSS-R) score of intermediate or higher\r\n** Secondary MDS with any IPSS score\r\n** Chronic myelomonocytic leukemia (CMML)\r\n* Lymphoproliferative disease:\r\n** Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or persistent) cytotoxic therapy refractory or with less than 6 months duration of complete response (CR) between courses of conventional therapy\r\n** Multiple myeloma (MM) progressive disease after auto bone marrow transplantation (BMT), tandem allo after prior auto\r\n** Waldenstrom’s macroglobulinemia (failed one standard regimen)\r\n** T or B cell lymphoma with poor risk features\r\n** Hodgkin disease:\r\n*** Received and failed frontline therapy\r\n*** Failed or not eligible for autologous transplantation
Diagnosis of hematologic malignancy (i.e. acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma) in complete remission at the time of transplant
Burkitt lymphoma/leukemia
Must have one of the following hematologic malignancies: a. Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, 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. b. Myelodysplastic syndrome (MDS): MDS International Prognostic Scoring System (IPSS) INT-1 will be enrolled only if the subjects have failed previous leukemia treatments and are transfusion-dependent. MDS may be primary or therapy related, including patients that will be considered for transplant. Including the following categories: 1) Revised IPSS intermediate and high risk groups, 2) MDS with transfusion dependency, 3) Failure to respond or progression of disease on hypomethylating agents, 4) Refractory anemia with excess of blasts, 5) Transformation to acute leukemia, 6) Chronic myelomonocytic leukemia, 7) Atypical MDS/myeloproliferative syndromes, 8) Complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p). c. Acute lymphoblastic leukemia (ALL) patients with the following will be considered: 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 which excludes > 7 chromosomal abnormalities, 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), or relapsed double hit lymphoma. Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease with progression after standard of care therapy or have failed/been intolerant to ibrutinib. Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase. Hodgkin's disease (HD): Induction failure after the first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease.
Patients with history of CD 19 positive B-lymphoid malignancies (acute lymphoblastic leukemia [ALL], chronic lymphocytic leukemia [CLL], non-Hodgkin's lymphoma [NHL]) who have received at least 2 lines of standard chemoimmunotherapy or targeted therapy and have persistent disease.
Patients with Burkitt lymphoma/leukemia
The following malignancies will be considered eligible if progressive or persistent:\r\n* Chronic lymphocytic leukemia (CLL)\r\n* Non-Hodgkin lymphoma (NHL)\r\n* Hodgkin lymphoma (HL)\r\n* Multiple myeloma (MM)\r\n* Acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL])\r\n* Myelodysplastic syndrome (MDS)\r\n* Myeloproliferative neoplasms (MPN)\r\n* Chronic myeloid leukemia (CML)
Diagnosed with one of the following high-risk malignancies, which require hematopoietic cell transplant (HCT) but do not have an available human leukocyte antigen (HLA)-matched (8/8) related or unrelated donor\r\n* High risk acute lymphoblastic leukemia (ALL) in first complete remission (CR1) or greater\r\n* High risk acute myelogenous leukemia (AML) in CR1 or greater\r\n* High risk undifferentiated acute leukemia\r\n* High risk myelodysplastic syndrome (MDS)\r\n* Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase inhibitors (TKIs) or in accelerated, blastic phase, or in second or subsequent chronic phase\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Lymphoma, (Hodgkin and non-Hodgkin lymphoma [NHL] including marginal zone, follicular lymphoma, chemotherapy-sensitive large-cell, mantle cell lymphoma, gray zone, and Burkitt’s lymphoma in remission)
IMMUNE RECONSTITUTION STUDY ONLY: Diagnosed with one of the following high-risk malignancies, which require HCT but do not have an available HLA-matched (8/8) related or unrelated donor\r\n* High risk acute lymphoblastic leukemia (ALL) in CR1 or greater\r\n* High risk acute myelogenous leukemia (AML) in CR1 or greater\r\n* High risk myelodysplastic syndrome (MDS)\r\n* Chronic myelogenous leukemia (CML) failing or intolerant to TKIs or in accelerated, blastic phase, or in second or subsequent chronic phase\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Lymphoma, (Hodgkin and NHL including marginal zone, follicular lymphoma, chemotherapy-sensitive large-cell, mantle cell lymphoma, gray zone, and Burkitt's lymphoma in remission
Patients with high risk myeloid or lymphoid malignancies prior to stem cell transplant with increased risk of disease relapse after stem cell transplant, including but not limited to conditions listed below\r\n* Refractory acute myelogenous or lymphoid leukemia\r\n* Relapsed acute myelogenous or lymphoid leukemia\r\n* Myelodysplastic syndromes with 5% or more blasts or with residual dysplastic changes prior to stem cell transplant, or with poor risk cytogenetic changes, such as -5, -7 or complex karyotype, or with poor molecular mutations, especially p53 mutation\r\n* Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase\r\n* Recurrent or refractory malignant lymphoma or Hodgkin’s disease with high risk relapse features or not in complete remission\r\n* High risk chronic lymphocytic leukemia not in complete remission or with high risk relapse features, such as p53 mutation, or 17p deletion et al.\r\n* Acute leukemia (including AML, ALL) with minimal residual disease determined by accepted methods, including multiple color flow cytometry; next generation sequencing (NGS) or molecular testing\r\n* Acute leukemia with poor risk cytogenetic changes
The patient must have a disease (listed below) with treatment-responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:\r\n* Acute leukemia – acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL)\r\n* Chronic leukemia – chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL)\r\n* Myelodysplasia\r\n* Myelofibrosis\r\n* Lymphoma – non-Hodgkin's lymphoma (NHL) and Hodgkin’s disease\r\n* Plasma cell disorder, including myeloma, Waldenstrom’s macroglobulinemia
Patients with high-risk hematologic malignancies with anticipated poor prognosis with non transplant therapy, including those in remission or with induction failure and after treated or untreated relapse; Diagnoses to be included a) Acute myeloid leukemia; b) Acute lymphocytic leukemia; c) Chronic myeloid leukemia; d) Chronic lymphoproliferative disorder; e) Myelodysplastic syndrome; f) Myeloproliferative syndromes; g) Non-Hodgkin's lymphoma; h) Hodgkin's Lymphoma; i) Multiple myeloma
Any of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic hematopoietic cell transplantation (HCT) (this includes any stage of disease - such as refractory due to induction failure, refractory in relapse, or in any complete remission (CR) - as long as the hematologic malignancy remained persistent or returned after a previous allogeneic HCT): acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), myeloid sarcoma, chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)
Patients at least eighteen (18) years of age with histologically or cytologically proven Multiple Myeloma (MM), Hodgkins Disease (HD), Non-Hodgkins Lymphoma (NHL), Chronic Myelogenous Leukemia (CML), Acute Lymphocytic Leukemia (ALL), Acute Myelogenous Leukemia (AML) and Chronic Lymphocytic Leukemia (CLL), who have responded to standard, first-line antineoplastic therapy, as defined using standard response criteria for the specific hematologic malignancy (HM), and have no additional potentially curative therapeutic intervention available, will be eligible to participate in this study.
One of the following diagnoses:\r\n* Acute myelogenous leukemia (AML) in 1st or subsequent remission\r\n* Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission\r\n* Chronic myelogenous leukemia (CML) in chronic or accelerated phase\r\n* Non-Hodgkin lymphoma (NHL) or Hodgkin’s disease (HD) in 2nd or greater complete remission, partial remission\r\n* Chronic lymphocytic leukemia (CLL)\r\n* Multiple myeloma (MM)\r\n* Myelodysplastic syndrome (MDS)\r\n* Myeloproliferative neoplasm (MPN) excluding primary or secondary myelofibrosis
Any of the following high risk or recurrent hematological malignancies: \r\n* Hodgkin lymphoma (HL) \r\n* Non-Hodgkin lymphoma (NHL) \r\n* Chronic lymphocytic leukemia (CLL) \r\n* Multiple myeloma (MM) \r\n* Acute myelogenous leukemia (AML) \r\n* Acute lymphocytic leukemia (ALL)\r\n* Chronic myelogenous leukemia (CML)\r\n* Myelodysplastic syndrome (MDS)\r\n** Note: determination that the malignancy is high risk will be made by the investigator
Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin’s lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
Has a myeloid or lymphoid malignant disease that is treated with TLI and ATG reduced-intensity conditioning for allogeneic transplant (any of the following: acute myeloid leukemia [AML]; chronic lymphocytic leukemia [CLL]; B or T cell non-Hodgkin lymphoma [NHL]; Hodgkin lymphoma [HL]; myelodysplastic syndrome (MDS); or myeloproliferative disease syndrome [MPD])
Patients with neoplastic hematological disorders with indication of allogeneic transplant according to the National Comprehensive Cancer Network (NCCN) or other standard guidelines as follows:\r\n* Acute lymphoblastic leukemia (ALL) with high-risk features or relapsed disease.\r\n* Hodgkin or non-Hodgkin lymphoma (HL or NHL): relapsed disease where remission duration is less than 1 year, relapse after previous autologous transplant, or failure to achieve complete remission (CR) with chemotherapy\r\n* Myeloid malignancy (acute myeloid leukemia [AML] with intermediate/high-risk features [per NCCN criteria] or relapsed disease, OR chronic myeloid leukemia [CML] in hematological remission or chronic phase)
INCLUSIONS FOR SCREENING AND LEUKAPHERESIS:\r\n* Patients with CD19 expressing acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL)\r\n* Ability to understand and provide informed consent\r\n* Not human immunodeficiency virus (HIV) infected
By definition, patients with hematological malignancies or dyscrasias that require HSCT as part of cure-directed therapy are by definition high-risk and can be treated on this protocol; examples of high risk patients include but are not limited to: \r\n* Acute myeloid leukemia with high risk features as defined by: \r\n** Age greater than or equal to 60 \r\n** Secondary acute myeloid leukemia (AML) (prior therapy or hematologic malignancy) \r\n** Normal cytogenetics but fms-related tyrosine kinase 3 (FLT3)/internal tandem duplication (ITD) positive \r\n** Any relapse or primary refractory disease \r\n** Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q), (11q), (3q), (21q), (17p), t(6;9), t(6;11), t(11;19), +8, del(12p), inv(3), t(10;11), -17, 11q 23 \r\n** Any single autosomal monosomy\r\n* Acute lymphoid leukemia in 1st or 2nd morphological remission; ALL with any morphological evidence of disease will not be eligible\r\n* Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes\r\n* Hodgkin’s or Non-Hodgkin’s lymphoma in 2nd or greater remission or with persistent disease\r\n* Myeloma with evidence of persistent disease after front-line therapy\r\n* Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy \r\n* Myelofibrosis and chronic myelomonocytic leukemia (CMML) \r\n* Essential thrombocytopenia or polycythemia vera with current or past evidence of evolution to acute leukemia\r\n* Patients with chronic lymphocytic leukemia (CLL), follicular non-Hodgkin lymphoma (NHL), or other lymphoid malignancies who have highly adverse cytogenetics (such as p53 deletion), are chemo-insensitive, are not responsive to highly effective novel treatments such as chimeric antigen receptor T-lymphocytes (CART) or Ibrutinib, or who have transformed disease\r\n* Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse\r\n* Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history; examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen\r\n* Patients with aplastic anemia may be treated on this protocol, with outcomes reported descriptively
Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied; patients will be considered high-risk if they have any of the following:\r\n* Eastern Cooperative Oncology Group (ECOG) performance status of =< 2\r\n* Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st complete remission (CR); second or greater CR, 1st relapse; any Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)\r\n* Chronic myelogenous leukemia (CML) 2nd chronic phase, accelerated phase, or blastic phase\r\n* Myelodysplastic syndromes (MDS) with International Prognostic Scoring System (IPSS) of intermediate 2 or greater\r\n* Any myeloproliferative disorder\r\n* Hodgkin lymphoma: relapsed, refractory, or primary induction failure\r\n* Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT\r\n* Other conditions not listed will be assessed as high-risk by the principal investigator (PI)
Hematologic malignancy (e.g. acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], B cell non-Hodgkin's lymphoma [B-NHL])
Patients with Burkitt lymphoma/leukemia
Patients must have histologic confirmation of relapsed and or refractory hematologic malignancy, locally advanced or metastatic colon/rectal carcinoma, or refractory and/or relapsed soft tissue sarcomas and have failed at least one standard line of therapy; patients will be eligible if they have either declined standard treatment regimens or if there is no standard approach to curative salvage therapy per National Comprehensive Cancer Network (NCCN) guidelines in the setting of relapsed/refractory disease; in addition, patients for whom a potential 29-day delay in treatment will not interfere with the subject’s potential therapeutic options can be eligible per the treating physician's discretion\r\nMalignancies can include:\r\n* Acute myeloid leukemia\r\n* Myelodysplastic syndrome\r\n* Acute lymphoblastic leukemia\r\n* Chronic myeloid leukemia\r\n* Chronic lymphocytic leukemia\r\n* Non Hodgkin lymphoma\r\n* Hodgkin lymphoma\r\n* Myeloproliferative syndromes\r\n* Plasma cell myeloma\r\n* Colon/rectal carcinoma\r\n* Sarcomas including but not limited to Ewing’s sarcoma and rhabdomyosarcoma
Non-Hodgkin lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple myeloma demonstrating chemosensitive disease
Lymphoid malignancies requiring allogeneic hematopoietic cell transplantation\r\n* Multiple myeloma including primary or secondary plasma cell leukemia and secondary amyloidosis\r\n* Lymphomas and related chronic lymphoid proliferative disorders: Hodgkin’s lymphoma, non-Hodgkin’s lymphoma of any types (B-cell, T-cell, null/natural killer [NK]-cell type), chronic lymphocytic leukemia (CLL), pro-lymphocytic leukemia (PLL), hairy-cell leukemia, large granular lymphocytic leukemia\r\n* Waldenstrom’s macroglobulinemia/lymphoplasmacytic lymphoma\r\n* Acute lymphoblastic leukemia (ALL) of any types
Primary cancer is leukemia, lymphoma, or myeloma
INCLUDING: any non-Hodgkin's B cell malignancy such as chronic lymphocytic leukemia (CLL) and rare non-Hodgkin's B- cell subtypes such as hairy cell leukemia, Waldenström macroglobulinemia (WM), mantle cell leukemia (MCL), and transformed NHL histologies
Subject has leukemia or lymphoma
Eligible diagnoses:\r\n* Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia (CMML) with at least one of the following poor-risk features:\r\n** Poor-risk cytogenetics\r\n** International Prognostic Scoring System (IPSS) score of intermediate (INT)-2 of greater\r\n** Treatment-related or secondary MDS\r\n** MDS diagnosed before age 21\r\n** Progression on or lack of response to standard deoxyribonucleic acid (DNA)-methyltransferase inhibitor therapy\r\n** Life-threatening cytopenias, including those requiring frequent transfusions\r\n* Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p deletion, or with progression < 6 months after second or greater treatment regimen; must have the following to be an acceptable candidate as well:\r\n** =< 20% of bone marrow cellularity involved by SLL/CLL (to lower risk of graft rejection)\r\n** No lymph nodes >= 5 cm in any dimension\r\n** No massive splenomegaly, defined as > 6 cm below the left costal margin\r\n* T-cell prolymphocytic leukemia (PLL) in partial remission (PR) or better prior to transplantation; must also have =< 20% of bone marrow cellularity involved by PLL (to lower risk of graft rejection)\r\n* Interferon- or tyrosine kinase-refractory chronic myelogenous leukemia (CML) in first chronic phase, tyrosine kinase inhibitor (TKI)-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase\r\n* Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)\r\n** Intermediate-2 or high risk score by Dynamic International Prognostic Scoring System (DIPSS) plus is required for a diagnosis of myelofibrosis\r\n* Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen, based on the International Myeloma Working Group (IMWG) criteria\r\n* Hematologic malignancy in complete remission with minimal residual disease (MRD) non detectable OR detectable by conventional cytogenetics, fluorescence in situ hybridization (FISH), flow cytometry, or molecular testing or hematologic malignancies in partial remission
Refractory or relapsed chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) or non-Hodgkin lymphoma (NHL) (including those of T cell origin)
Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning:\r\n* Refractory acute myelogenous or lymphoid leukemia\r\n* Relapsed acute myelogenous or lymphoid leukemia\r\n* Myelodysplastic syndromes with 5% or more blasts\r\n* Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase\r\n* Recurrent or refractory malignant lymphoma or Hodgkin’s disease with less than a partial response at transplant\r\n* High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen\r\n* Diseases in response or remission at high risk of relapse at the discretion of the attending physician: some examples include but are not limited to:\r\n** Acute myeloid leukemia (AML) in remission with monosomy 5 or 7, deletion of 5q or 7q, 11q23 mixed-lineage leukemia (MLL) rearrangement or complex karyotype (>= 3 chromosome abnormalities)\r\n** Non-Hodgkin's lymphoma (NHL) in response that is double hit or triple hit (which are characterized by a recurrent chromosome translocation in combination with a v-myc avian myelocytomatosis viral oncogene homolog [MYC]/8q24 breakpoint; these include but not limited to B-cell chronic lymphocytic leukemia [CLL]/lymphoma [BCL]2+/MYC+; BCL6+/MYC+; cyclin D1 (CCND1)+/MYC+; and BCL2+/BCL6+/MYC+)\r\n** Bi-phenotypic lineage leukemia\r\n** CLL with 17p deletion\r\n** Acute lymphoblastic leukemia (ALL) with t(4,11) et al.
Diagnosis of high risk hematological malignancy:\r\n* Any acute leukemia in first complete remission (CR) considered at high risk for relapse, or second or third CR, or relapse/refractory less than 10% blasts in bone marrow, or aplasia post-therapy; this includes de novo acute leukemia or acute leukemia that is therapy related or arising from an antecedent hematologic disorder including myelodysplasia (MDS), chronic myeloid leukemia (CML) or other myeloproliferative disorder\r\n* Juvenile myelomonocytic leukemia (JMML) in CR, or relapse with less than 10% bone marrow blasts \r\n* CML with tyrosine kinase inhibitor failure in chronic or accelerated phase or evolved to acute leukemia (blast crisis, see above)\r\n* MDS or other myeloproliferative disorder with life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence, or patients with aplasia, or patients with excess blasts less than 10% blasts in the bone marrow at work-up\r\n* Aggressive lymphoma: patients in first complete remission (CR1) with disease at high risk of relapse or CR2-3 \r\n* Indolent lymphoma or chronic lymphocytic leukemia (CLL): any disease status provided any transformed component is in CR\r\n* Hodgkin lymphoma that is primary refractory or relapsed not suitable for other therapy and in partial remission (PR) or CR or small volume stable disease
Recipients of first ASCT from related or unrelated donor for the treatment of hematologic malignancies (acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome, Hodgkin and non-Hodgkin lymphoma) who are 1-antigen or 1-allele mismatched or fully matched at human leukocyte antigen (HLA)-A, -B, -C and –DR as defined by high resolution typing
Patients who are considered candidates for an allogeneic stem cell transplantation as treatment for any of the following hematologic disorders:\r\n* Acute leukemia\r\n* Myelodysplastic syndrome\r\n* Other myeloproliferative disorder (i.e. myelofibrosis, chronic myelomonocytic leukemia, or chronic myelogenous leukemia)\r\n* Non Hodgkin's lymphoma\r\n* Hodgkin's disease\r\n* Multiple myeloma
Patients with high-risk hematologic malignancies with anticipated poor prognosis with non-transplant therapy, including those in remission or with induction failure and after treated or untreated relapse; diagnoses to be included are:\r\n* Acute myeloid leukemia\r\n* Acute lymphocytic leukemia\r\n* Chronic myeloid leukemia\r\n* Chronic lymphocytic leukemia\r\n* Myelodysplastic syndrome \r\n* Myeloproliferative syndromes\r\n* Non-Hodgkin lymphoma\r\n* Hodgkin lymphoma\r\n* Multiple myeloma
The following diseases will be permitted although other diagnoses can be considered if approved by Patient Care Conference (PCC) or the participating institutions’ patient review committees and the principal investigators\r\n* Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B cell NHL: not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT\r\n* Mantle cell NHL: may be treated in first complete remission (CR); (diagnostic lumbar puncture [LP] required pre-transplant)\r\n* Low grade NHL: with < 6 month duration of CR between courses of conventional therapy\r\n* CLL: must have either: \r\n** Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing FLU (or another nucleoside analog, e.g. 2-Chlorodeoxyadenosine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); \r\n** Failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or \r\n** Have “17p deletion” cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; or\r\n** Patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL\r\n* Hodgkin lymphoma: must have received and failed frontline therapy\r\n* Multiple myeloma: must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted\r\n* Acute myeloid leukemia (AML): must have < 5% marrow blasts at the time of transplant\r\n* Acute lymphocytic leukemia (ALL): must have < 5% marrow blasts at the time of transplant\r\n* Chronic myeloid leukemia (CML): patients in 1st chronic phase (CP1) must have failed or be intolerant of tyrosine-kinase inhibitors (TKI); patients beyond CP1 will be accepted if they have < 5% marrow blasts at time of transplant  \r\n* Myelodysplasia (MDS)/myeloproliferative syndrome (MPS): patients must have < 5% marrow blasts at time of transplant \r\n* Waldenstrom’s macroglobulinemia: must have failed 2 courses of therapy
Patients who are to receive an allogeneic hematopoietic cell transplant as treatment for a leukemia or myelodysplastic syndrome that has an expected risk of relapse exceeding 30% will be eligible to have donor-derived WT1 peptide sensitized T cells generated prior to or at the time of transplant for immediate use post transplant at such time that the patient is found to have minimal residual disease or relapse; this includes patients with:\r\n* Acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or MDS refractory to primary induction therapy\r\n* ALL or AML at any stage later than first (1 degree) relapse\r\n* Chronic myelogenous leukemia (CML) secondary (2 degree) or greater chronic phase after chemotherapy\r\n* CML in persistent accelerated phase or blast crisis\r\n* High risk MDS (refractory anemia with excess blasts [RAEB] and RAEB in transformation [T]) which has failed to respond or has recurred following induction chemotherapy
Patients with a diagnosis of leukemia, lymphoma, or myeloma
One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myeloid sarcoma, chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)
One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT: \r\n* Acute lymphoblastic leukemia (ALL)\r\n* Acute myeloid leukemia (AML) (including myeloid sarcoma)\r\n* Chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), Hodgkin or non-Hodgkin lymphoma (NHL)
Allogeneic hematopoietic cell transplant for hematologic malignancy (i.e. leukemia, lymphoma including acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], chronic myelogenous leukemia [CML], non-Hodgkin lymphoma [NHL], Hodgkin lymphoma [HL]) in complete remission; myelodysplastic syndrome (active dysplasia and/or blasts are permitted, but must not have active leukemia) or idiopathic severe aplastic anemia (SAA)
Patients must have one of the following documented diseases:\r\n* Chronic myelogenous leukemia\r\n* Chronic lymphocytic leukemia\r\n* Multiple myeloma\r\n* Myelodysplasia\r\n* Myeloproliferative disorder\r\n* Non-Hodgkin's lymphoma\r\n* Hodgkin's disease\r\n* Acute myelogenous leukemia\r\n* Acute lymphoblastic leukemia\r\n* Acute biphenotypic leukemia
Patients must meet diagnostic criteria of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), myelodysplastic syndrome (MDS), myelofibrosis, or severe aplastic anemia; patients will be allowed on study if they are deemed eligible for allogeneic (allo) HCT regardless of remission status
Planned peripheral blood stem cell (PBSC) or bone marrow (BM) HCT for the treatment of the following hematologic malignancies:\r\n* Lymphoma (Hodgkin and non-Hodgkin)\r\n* Myelodysplastic syndrome\r\n* Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in hematologic remission by bone marrow and peripheral blood; persistent lymphadenopathy on computed tomography [CT] or CT/positron emission tomography [PET] scan without progression is allowed)\r\n* Acute myeloid leukemia in first or second remission\r\n* Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase\r\n* Other hematologic malignancies judged appropriate by the clinical principal investigators (PIs), including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded\r\n** Adult cases of multiple myeloma (MM) are excluded; adults with aplastic anemia are excluded; patients undergoing a second haploHCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
Planned HCT for the treatment of the following hematologic malignancies:\r\n* Lymphoma (Hodgkin and non-Hodgkin)\r\n* Myelodysplastic syndrome\r\n* Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status needs to be in hematologic remission by bone marrow and peripheral blood; persistent lymphadenopathy on computed tomography [CT] or CT/positron emission tomography [PET] scan without progression is allowed)\r\n* Acute myeloid leukemia in first or second remission\r\n* Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase\r\n* Other hematologic malignancies including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
Planned HCT for the treatment of the following hematologic malignancies:\r\n* Lymphoma (Hodgkin and non-Hodgkin)\r\n* Myelodysplastic syndrome\r\n* Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in hematologic remission by bone marrow and peripheral blood; persistent lymphadenopathy on computed tomography [CT] or CT/positron emission tomography [PET] scan without progression is allowed)\r\n* Acute myeloid leukemia in first or second remission\r\n* Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase\r\n* Other hematologic malignancies including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded\r\n* Patients undergoing a second allogeneic (allo) HCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
Patients with history of hematologic malignancies, including leukemia, myeloma, myeloproliferative disease, lymphoma, or myelodysplastic diseases
Diagnosis of lymphoma or leukemia as documented in medical record
Leukemia, lymphoma, and myeloma
Patients that are high risk for TLS or potential/intermediate risk for TLS as described below:\r\n* High risk: Hyperuricemia of malignancy (uric acid levels > 7.5); or diagnosis of very aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia, chronic myelogenous leukemia (CML) in blast crisis; high grade myelodysplastic syndrome only if they have > 10% bone marrow blast involvement and given aggressive treatment similar to acute myeloid leukemia (AML)\r\n* Potential risk: Diagnosis of aggressive lymphoma/leukemia based on (REAL) classification; plus one or more of the following criteria: lactate dehydrogenase (LDH) >= 2 x upper limit of normal (UNL); stage III-IV disease; stage I-II disease with at least 1 lymph node/tumor > 5 cm in diameter; for patients with potential/intermediate risk for TLS-only those planned to receive alternating regimens (or non-standard regimens) in 2 cycles (example; rituximab-hyperfractionated cyclophosphamide-vincristine [vincristine sulfate]-Adriamycin [doxorubicin hydrochloride]-dexamethasone [R-Hyper-CVAD] alternating with methotrexate/arabinofuranosyl cytidine [cytarabine] [MTX/ARA-C]) will be eligible
RECIPIENT: Planned HCT for the treatment of the following hematologic malignancies: lymphoma (Hodgkin and non?Hodgkin), myelodysplastic syndrome, acute lymphoblastic leukemia in first or second remission, acute myeloid leukemia in first or second remission, chronic myelogenous leukemia (in first chronic or accelerated phase, or in second chronic phase), chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis (City of Hope [COH] only). Patients with multiple myeloma are excluded
The patient must have a diagnosis of one of the following (one must be yes):\r\n* Acute myeloid leukemia (AML)\r\n* Acute lymphoblastic leukemia (ALL)\r\n* Chronic myelogenous leukemia (CML) (chronic phase intolerant or unresponsive to tyrosine kinase inhibitors, accelerated phase, history of blast crisis)\r\n* Myelodysplastic syndrome (MDS)\r\n* Myeloproliferative neoplasm (MPN)\r\n* Chronic myelomonocytic leukemia (CMML)\r\n* Non-Hodgkin lymphoma (NHL)\r\n* Hodgkin lymphoma (HL) (received and failed frontline therapy or failed autologous transplantation or inability to collect enough peripheral blood stem cells [PBSC] for autologous hematopoietic cell transplant [auto-HCT])\r\n* Multiple myeloma (MM)\r\n* Waldenstrom’s macroglobulinemia\r\n* Severe aplastic anemia
Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, myeloproliferative neoplasms, Hodgkin lymphoma, or non-Hodgkin lymphoma requiring a matched allogeneic HSCT
Subjects must have one of the following disease categories:\r\n* Acute myeloid leukemia (AML) beyond 2nd remission or relapsed/refractory disease\r\n* Acute lymphoblastic leukemia (ALL) beyond 2nd remission or relapsed/refractory disease\r\n* Chronic myeloid leukemia (CML) beyond 2nd chronic phase or in blast crises\r\n* Myelodysplastic syndrome (MDS)\r\n* Myeloproliferative disorders including myeloid metaplasia and myelofibrosis\r\n* High risk non-Hodgkin’s lymphoma (NHL) in first remission\r\n* Relapsed or refractory NHL\r\n* Hodgkin’s lymphoma (HL) beyond first remission
Malignant disorders:\r\n* Chronic myeloid leukemia (CML) (chronic phase, accelerated phase or blast crisis)\r\n* Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML)\r\n* Acute lymphoblastic leukemia (ALL)\r\n* Lymphoma (Hodgkin’s and non-Hodgkin’s)
Hematologic malignancies - Acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM) - in complete remission (CR)\r\n* Complete remission is defined per morphologic, cytogenetic, fluorescence in situ hybridization (FISH), molecular, and radiographic imaging studies appropriate for each condition listed
Have lymphoma or leukemia
Patients with Burkitt's leukemia/lymphoma.
Participants must have pathologically confirmed, newly diagnosed high-risk acute myeloid leukemia, as defined by at least one of the following criteria:\r\n* Age >= 65 years\r\n* Age >= 18 years with adverse risk karyotype, as per European Leukemia Net Guidelines\r\n* Age >= 18 years with antecedent or underlying myelodysplastic syndrome, chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm\r\n* Age >=18 years with acute myeloid leukemia (AML) with myelodysplastic syndrome (MDS)-related changes\r\n** Note: For patients in category A, a sample to evaluate patient cytogenetics will be sent at the time of diagnosis per standard clinical care and the absence of favorable risk cytogenetics must be confirmed by day 8; if the cytogenetic analysis reveals that the patient harbors favorable risk cytogenetics, or if the cytogenetic results are not received prior to day 8, the participant will be removed from the study; patients removed due to presence of favorable cytogenetics would be considered to be inevaluable and will be replaced; in addition, patients who receive less than half of their total alisertib dose during induction would be considered to be inevaluable and will be replaced
Acute myeloid leukemia (AML): must have < 5% marrow blasts at the time of transplant
Relapsed or refractory acute myeloid leukemia
Diagnosis of acute myeloid leukemia (i.e. >= 20% peripheral or marrow blasts)
Relapsed or refractory acute myelocytic leukemia (AML) with nucleophosmin-1 (NPM1) mutations and no available therapies.
Relapsed and refractory acute myeloid leukemia (Cohort 1)
Newly diagnosed acute myeloid leukemia in older patients (>= 65 years) not candidates for intensive induction chemotherapy (Cohort 2)
Known prior progression to acute myeloid leukemia (AML), defined by at least 20% blasts in the blood or bone marrow.
Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or second remission. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, < 5% blasts in the bone marrow and absence of extramedullary disease including CNS involvement.
Known prior progression to acute myeloid leukemia (AML) defined by at least 20% blasts in the blood or bone marrow.
Very high risk pediatric/young adult patients with acute myeloid leukemia (AML): Patients =< 25 years, however, are eligible with (M2 marrow) with =< 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately
Confirmed diagnosis of relapsed or refractory acute leukemia (acute myeloid leukemia, acute lymphoblastic leukemia, blast crisis of chronic myeloid leukemia [CML], secondary AML from prior myelodysplastic syndrome [MDS] / myeloproliferative neoplasm [MPN]); minimum of 5% blasts in the bone marrow or 10% blasts in circulation
This study is open to patients with acute myeloid leukemia (AML) evaluated within 30 days of the start of conditioning regimen and in first or second complete remission (CR)
Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML)
Patients can be in chronic phase (CP) with bone marrow (BM) blast count =< 10% or after progression to acute myeloid leukemia (AML) and achieved =< 5% BM blasts (morphologic complete remission [CR] prior to transplant);
Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.
Experimental therapies for MDS or Acute Myeloid Leukemia (AML).
Participant has the following: a. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 for Acute Myeloid Leukemia.
Relapsed acute myeloid leukemia
Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) in confirmed relapse based on bone marrow examination after allogeneic HCT; biopsy confirmed myeloid sarcoma or extramedullary AML may also be considered
Acute myeloid leukemia (AML) – must have < 5% marrow blasts at the time of transplant
Patients ?18 and ?75 years old with relapsed or primary refractory acute myeloid leukemia.
Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia or R/R acute lymphoblastic leukemia for which no available standard therapies are indicated or anticipated to result in a durable response
Patients can be in chronic phase (CP) with bone marrow (BM) blast count =< 10% or after progression to acute myeloid leukemia (AML) and achieved =< 5% BM blasts (morphologic complete remission [CR] prior to transplant)
Diagnosis of acute myeloid leukemia (AML) (other than acute promyelocytic leukemia [APL]) with refractory/relapsed disease; patients with relapsed/refractory high-risk ([intermediate-2 or higher by International Prognostic Scoring System [IPSS] and/or >= 10% blasts]). Myelodysplastic syndrome (MDS) will also be eligible. (Treatment approach for relapsed/refractory AML is very similar to that of high risk MDS)
Diagnosis of untreated “high-grade” myeloid neoplasm (>= 10% myeloid blasts by morphology in bone marrow and/or peripheral blood) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; patients with acute leukemias of ambiguous lineage are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available
Prior therapy with hydroxyurea, interferon, anagrelide, ruxolitinib, hypomethylating agents, revlimid, thalidomide, steroids, other JAK inhibitors is allowed; for acute myeloid leukemia (AML) patients who are back in chronic phase myeloproliferative neoplasm (MPN), prior induction therapy is allowed
Pathological confirmation by bone marrow documenting the following:\r\n* Acute myeloid leukemia (AML) which has relapsed after complete remission\r\n* AML which has been refractory to two prior induction attempts\r\n* Acute lymphoblastic leukemia (ALL) which has relapsed after complete remission\r\n* ALL which has been refractory to two prior induction attempts
Relapsed ALL, biphenotypic/bilineal leukemia, or acute myeloid leukemia (AML) with =< 10% blasts in the bone marrow prior to transplantation
All patients with histologically or cytologically confirmed relapsed or refractory acute myeloid leukemia (AML) (except acute promyelocytic leukemia) or relapsed or refractory high-risk myelodysplastic syndrome (HRMDS) (intermediate 2 [Int-2] or higher risk by International Prognostic Scoring System [IPSS]); patients with chronic myelomonocytic leukemia (CMML) can be enrolled if they can be classified as HRMDS using MDS criteria; patients should not have received more than one salvage therapy; second induction regimen or stem cell transplant in remission will be considered salvage therapy; refractory subjects, up to second consecutive salvage
Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia or granulocytic sarcoma
Acute myelogenous leukemia\r\n* In first complete remission (CR1) in addition to one of the criteria outlined\r\n* Second or greater complete remission\r\n* Secondary acute myeloid leukemia (AML) from antecedent myeloid neoplasm, myelodysplasia, or previous chemotherapy (chemo) or radiotherapy
Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia
Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second or above allogeneic (allo)-stem cell transplant (SCT) using the same donor or different donor for disease relapse; patients with other hematologic malignancies, including acute lymphoblastic leukemia (ALL), will be at the discretion of the investigators with discussion with the principal investigator (PI)
For salvage cohort: patients with previously treated, relapsed or refractory AML, acute biphenotypic leukemia, or CML in myeloid blast phase are eligible
Patients with acute myeloid leukemia (AML) in first remission after one course of induction and with favorable cytogenetics (t[8;21], inv 16, or t[15;17]) and/or molecular profile (nucleophosmin [NPM]1)
Acute myeloid leukemia in first remission with any of the following high risk features defined as:\r\n* Adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (> 3 abnormalities)\r\n* Preceding myelodysplastic or myeloproliferative syndrome\r\n* Presence of high risk molecular abnormalities including FLT3 mutations, DNMT3A, TET2; ras; kit\r\n* French–American–British (FAB) monosomy (M)6 or M7 classification\r\n* Treatment related acute myeloid leukemia (AML)\r\n* Residual cytogenetic or molecular abnormalities
Patients with >= 18 years of age with relapsed/refractory leukemia with a confirmed diagnosis of acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) who meet the following criteria: \r\n* Age 18-64: Salvage treatment failures only - defined as relapsed or refractory to after least 1 cycle of salvage therapy\r\n* Age >= 65: Refractory to or have relapsed after induction chemotherapy defined as no response to initial therapy\r\n** Given the clinical activity and use of hypomethylating agents in AML patients, for all AML populations, initial therapy and salvage therapy may include hypomethylating agents; furthermore, patients >= 65 with hematologic malignancies including chronic myelomonocytic leukemia (CMML) or myelodysplasia (MDS) that transform to acute leukemia while actively receiving hypomethylating agents (i.e. decitabine or azacytidine) will be considered induction failures and thus are eligible; for Philadelphia positive (Ph+) ALL, initial therapy and salvage therapy may include steroids and imatinib or dasatinib or nilotinib
Acute myeloid leukemia (AML) in 1st remission – for patients whose AML does not have ‘good risk’ cytogenetic features (i.e. t8;21, t15;17, inv 16)
High risk acute myelogenous leukemia or high risk myelodysplastic syndrome (Revised International Prognosis Scoring System [r-IPSS] score 3 or above) status post allogeneic bone marrow transplant from matched related or unrelated donors; high risk acute myeloid leukemia (AML) patients in this study are defined as AML patients with residual leukemia at the time of transplant, very poor cytogenetics (i.e. deletion 3 or monosomy 3, deletion 7 or monosomy 7 and complex cytogenetics) or secondary AML; patients with acute promyelocytic leukemia are not eligible for this study
Acute myeloid leukemia as defined by WHO criteria
Poor-risk acute leukemia in first remission, with remission defined as < 5% bone marrow blasts morphologically:\r\n* Acute myeloid leukemia (AML) with at least one of the following: AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative disorder, or secondary AML; presence of fms-related tyrosine kinase 3 (Flt3) internal tandem duplications; poor-risk cytogenetics: complex karyotype [>= 3 abnormalities], inv(3), t(3;3), t(6;9), myeloid/lymphoid or mixed-lineage leukemia (MLL) rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7; primary refractory disease\r\n* Acute lymphoblastic leukemia (ALL) (leukemia and/or lymphoma) with at least one of the following: adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL rearrangement; clear evidence of hypodiploidy; primary refractory disease\r\n* Biphenotypic leukemia
Acute myeloid leukemia (AML) after first relapse or with primary refractory disease
Diagnosis of untreated “high-grade” myeloid neoplasm (? 10% blasts in blood or bone marrow) or acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for  flow cytometry performed at the study institution should be considered; diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate
Patients must have one of the following diagnoses:\r\n* Acute myeloid leukemia fulfilling the criteria of the World Health Organization (WHO) classification, or\r\n* > 5% but < 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality [e.g., t(8;21), inv(16), t(9;11)], or\r\n* Myeloid sarcoma (also referred to as extramedullary myeloid tumor, granulocytic sarcoma, or chloroma), with or without evidence of a leukemia process in the bone marrow or peripheral blood, with confirmation of myeloid differentiation, or\r\n* High grade myelodysplastic syndrome (MDS) with greater than 5% blasts, or\r\n* Patients with treatment related myeloid neoplasms including AML and MDS, provided their cumulative anthracycline dose has not exceeded 230 mg/m^2 doxorubicin equivalents
Bone marrow blasts ?20%, indicating a diagnosis of acute myeloid leukemia (AML).
A diagnosis of acute myeloid leukemia (AML) according to the World Health Organization 2008 criteria with relapsed or refractory disease and ineligible for or have exhausted standard therapeutic options
Patients must have newly diagnosed, previously untreated acute myeloid leukemia (AML) (excluding M3)
Myeloid malignancies requiring allogeneic hematopoietic cell transplantation\r\n* Acute myeloid leukemia (AML) and acute leukemia of mixed or undetermined or ambiguous lineage\r\n* Myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD) (chronic myeloid leukemia [CML], primary myelofibrosis, post-polycythemic/post-thrombocythemic myelofibrosis), chronic myelomonocytic leukemia (CMMoL) and acute blastic transformation of these conditions
Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), who are eligible for stem cell transplant; remission defined as no circulating blasts, < 5% blasts in the bone marrow, normalization of previously detected cytogenetic abnormalities, no extramedullary disease
Patients must have histologically or cytologically documented relapsed and/or refractory acute myeloid leukemia
Subject has Relapsed or Refractory Acute Myeloid Leukemia (rrAML) after at least 2 prior induction attempts:
Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
Central confirmation of intermediate or poor risk status, based on Cytogenetics for Acute Myeloid Leukemia.
Acute myeloid leukemia associated with inv(16), t(8;21), t(16;16), t(15;17) karyotypes or molecular evidence of such translocations if not associated with a c-Kit mutation.
Acute myeloid leukemia (AML)
CD30 expressing acute myeloid leukemia (AML), as identified by flow cytometric analysis, or by immunohistochemistry when 2+ or 3+ staining is present in greater than or equal to 20% of the myeloblasts in the bone marrow specimen
Patients presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs (e.g. acute myeloid leukemia [AML])
Relapsed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) >= 60 days after allogeneic stem cell transplant (SCT)
Adults with acute myeloid leukemia (AML), excluding the M3 subtype (acute promyelocytic leukemia), that are not likely to respond to conventional therapy, including:\r\n* Relapsed or refractory AML after one to four prior induction regimens (not counting consolidation therapies while in complete response [CR], and not counting autologous transplant while in CR),\r\n* Newly diagnosed AML patient’s age not fit for standard therapy
Patients with < 20% bone marrow blasts are eligible if they have: \r\n* A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities\r\n* The unequivocal presence of megakaryoblasts, or\r\n* Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to WHO classification (2008) documented within 28 days prior to enrollment.
Acute myeloid leukemia (AML) diagnosed by morphologic, histochemical or cell surface marker criteria.
Patients must have histologic evidence of newly diagnosed acute myeloid leukemia (non-M3 AML) as documented by the presence of > 20% myeloid blasts in the bone marrow or a pathological diagnosis of granulocytic sarcoma, leukemia cutis or other pathologically confirmed extramedullary involvement of AML
Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including acute myeloid leukemia [AML] in complete remission [CR] and myelodysplastic syndrome with < 10% blasts in the bone marrow) unlikely to be cured by alternative therapies
Patients must have a diagnosis of AML or acute leukemia of ambiguous lineage according to World Health Organization (WHO) classification with >= 5% of disease in bone marrow (BM); patients with blast count < 5% are eligible if immunophenotype, molecular or cytogenetic signature are consistent with AML as determined by primary treating oncologist; patients with extramedullary disease, or biopsy-proven isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) are eligible regardless of marrow involvement
Untreated histologically confirmed acute myeloid leukemia OR advanced myelodysplastic syndrome (intermediate [INT]-2 or High risk) not previously treated with anthracycline-based chemotherapy OR a therapy-related myeloid neoplasm
Patients with the diagnosis of Acute Myeloid or Lymphocytic Leukemia (AML or ALL) in first or second complete remission.
Acute myeloid leukemia (AML) must have < 5% marrow blasts at the time of HCT
Patients must have one of the following three characteristics:\r\n* Acute myeloid leukemia fulfilling the criteria of the World Health Organization (WHO) classification\r\n* < 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality [e.g., t(8;21), inv(16), t(9;11)] \r\n* Myeloid sarcoma (also referred to as extramedullary myeloid tumor, granulocytic sarcoma, or chloroma), with or without evidence of a leukemic process in the bone marrow or peripheral blood, with confirmation of myeloid differentiation\r\n* Patients with secondary AML following treatment of primary malignancy are eligible
Relapsed/refractory acute myeloid leukemia following at least 2 but no more than 3 prior regimens
Relapsed/refractory acute myeloid leukemia (AML) except for acute promyelocytic leukemia
Patients with CD56 expressing hematological malignancy, as follows: cohort 1: CD56 expressing hematological malignancies including but not limited to acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS), natural-killer leukemia, acute lymphoblastic leukemia, accelerated and blast-phase chronic myeloid leukemia (CML) who have failed prior therapy or for which no standard therapy exists; cohort 2: patients with MF (either primary MF, post-polycythemia MF, or post-essential thrombocythemia MF) and CD56 expression who have been on ruxolitinib or JAK-inhibitor therapy for at least 12 weeks and deemed refractory or sub-optimal responders in the opinion of the treating physician; cohort 3: patients with pathological diagnosis of BPDCN with CD56 expression (frontline and relapsed/refractory)
Patients must have one of the following, histologically or cytologically confirmed:\r\n* Acute myeloid leukemia (AML) [non- acute promyelocytic leukemia (APL) AML]\r\n** If previously treated:\r\n*** AML that is relapsed or refractory to at least one prior line of therapy\r\n** If previously untreated, must meet all of the following:\r\n*** >= 60 years of age\r\n*** Secondary or therapy-related AML\r\n*** Does NOT bear favorable cytogenetic and/or molecular features, eg, core-binding factor abnormalities, FLT3 Internal Tandem Duplication (FLT3-ITD) negative/NPM1 mutated, biallelic CCAAT/enhancer binding protein alpha (CEBPA) mutation without FLT3-ITD\r\n* Chronic myeloid leukemia blast crisis (CML-BC)\r\n** Relapsed or refractory to at least one Bcr-Abl-TKI-containing regimen\r\n* Myelodysplastic syndrome (MDS), must meet all of the following:\r\n** Higher risk MDS [intermediate-2 or high risk by the original International Prognostic Scoring System (IPSS)]\r\n** Relapsed, refractory, or intolerant to at least one prior line of therapy containing hypomethylating agents (deoxyribonucleic acid [DNA] methyltransferase inhibitors)
Acute myeloid leukemia (AML), except those patients with RAEB-t who are not candidates for intensive AML therapy.
Have an unequivocal histologic diagnosis of acute myeloid leukemia (AML) (including secondary AML)
Not meeting WHO criteria for Polycythemia Vera (PV), Chronic Myeloid Leukemia (CML), Myledysplastic Syndrome (MDS), or other myeloid neoplasm
Diagnosis of relapsed or refractory AML with at least one prior treatment for acute myeloid leukemia and patients with diagnosis of acute myeloid leukemia in complete remission with high risk to relapse.
Expression of CD33 on more than 30% of bone marrow blasts at screening for patients with refractory or relapsed acute myeloid leukemia is required. CD33 positive expression of bone marrow blasts at the time of initial acute myeloid leukemia diagnosis is sufficient for those patients in complete remission with high risk to relapse.
Patients with refractory or relapsed acute myeloid leukemia > 5.000 blasts in the peripheral blood.
Anti-leukemia therapy within two weeks before first treatment with BI 836858, 4 weeks for biologics. Parallel treatment with Hydroxyurea ia allowed with refractory or relapsed acute myeloid leukemia patients.
Patients who are candidates for allogeneic stem cell transplantation (for patients with refractory or relapsed acute myeloid leukemia).
Morphologically confirmed acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL), including leukemia secondary to prior therapy or antecedent hematologic disorder (e.g., MDS or myeloproliferative disorders), who have failed to achieve CR or who have relapsed after prior therapy and are not candidates for potentially curative therapy
Participant has a relapsed or refractory hematologic malignancy (with any measurable disease) with FLT3-ITD or TKD mutations and one of the following diagnoses:\r\n* Acute myeloid leukemia (AML)\r\n* AML with prior myelodysplastic syndrome (MDS)\r\n* Myeloperoxidase (MPO)-positive mixed phenotype acute leukemia
Diagnosis: Patients must have documented relapsed/refractory ALL, AML, or acute leukemia of ambiguous lineage and meet the following criteria:
Acute myeloid leukemia, positive for CD33
Diagnosis of acute myeloid leukemia (AML) (other than acute promyelocytic leukemia) with refractory/relapsed disease; (patients must be primary refractory, in relapse 1, or in relapse 2); NOTE: patients with AML arising from prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) would be eligible even if they have not received treatment for the AML; NOTE: patients with relapsed/refractory acute lymphocytic leukemia (ALL) would also be eligible for the phase II part of the study; NOTE: use of hydroxyurea and/or up to 4 doses of cytarabine, for emergent cytoreduction is allowed
> 10% blasts or biopsy-documented leukemia cutis or myeloid sarcoma.
Previous diagnosis of CD123+ acute myeloid leukemia (AML), de novo or secondary.
Poor-risk acute leukemia in first remission, with remission defined as < 5% bone marrow blasts morphologically:\r\n* Acute myeloid leukemia (AML) with at least one of the following:\r\n** AML arising from myelodysplastic syndromes (MDS) or a myeloproliferative disorder, or secondary AML\r\n** Presence of FMS-like tyrosine kinase-3 (Flt3) internal tandem duplications\r\n** Poor-risk cytogenetics\r\n** Primary refractory disease\r\n* Acute lymphoblastic leukemia (ALL) (leukemia and/or lymphoma) with at least one of the following:\r\n** Poor-risk cytogenetics\r\n** Clear evidence of hypodiploidy\r\n** Primary refractory disease\r\n* Biphenotypic leukemia
Patients must have a diagnosis of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), acute lymphoblastic leukemia (ALL), infantile leukemia (either AML or ALL), AML with prior myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms, or biphenotypic leukemia; patients with treatment-related AML (t-AML) will be eligible, provided they meet all other eligibility criteria; current disease status must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must meet one of the following criteria:\r\n* First or greater relapse\r\n* Refractory to 1 or more courses of induction or reinduction chemotherapy\r\n* First or greater relapse after allogeneic hematopoietic stem cell transplantation (HSCT)
Acute leukemia patients (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], acute promyelocytic leukemia [APL], therapy-related myeloid neoplasm [tMN], high grade myelodysplastic syndrome [MDS])
Poor risk disease/disease status including: chronic myeloid leukemia (CML) in blast crisis, acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) beyond 2nd remission, multiple myeloma, and aplastic anemia
Patient must fit 1 of the following 2 categories:                          \r\n* Chemotherapy patients                \r\n** Planned to receive at least 2 consecutive cycles (not required to be the first 2 cycles) of intensive chemotherapy for either:\r\n*** De novo, relapsed or secondary acute myeloid leukemia (AML), or acute leukemia of ambiguous lineage treated with standard AML therapy\r\n*** Relapsed acute lymphoblastic leukemia (ALL)\r\n*** For the purposes of this study, “intensive chemotherapy” is defined as regimens that are predicted by the local investigator to cause neutropenia for > 7 days; examples include, but are not limited to, treatment with “4-drug induction” (anthracycline, vincristine, asparaginase, and steroid), high dose cytarabine, anthracycline/cytarabine, ifosfamide/etoposide, and clofarabine-containing regimens\r\n* Stem cell transplantation patients                \r\n** Planned to receive at least 1 myeloablative autologous or allogeneic HSCT\r\n** For the purposes of this study, myeloablative autologous and allogeneic HSCT are those in which the conditioning regimen is predicted by the local Investigator to cause neutropenia for > 7 days
Newly Diagnosed Acute Myeloid Leukemia (AML)
Relapsed/refractory acute myeloid leukemia (AML) patients who received standard of care cytarabine and mitoxantrone as their chemotherapy regimen
Acute myeloid leukemia arising de novo (per European LeukemiaNet)
Transformed acute myeloid leukemia (AML) with marrow fibrosis is allowed, if AML is in complete remission after induction therapy
Acute myeloid leukemia
Acute myeloid leukemia (AML) – must have < 5% marrow blasts at the time of transplant
Acute myeloid leukemia (AML)
DONOR: Patient with acute myeloid leukemia (AML) undergoing screening for potential URD HCT
DONOR: Potential URD undergoing screening to provide a HCT graft to a patient with acute myeloid leukemia (AML) at a participating institution
Relapsed or refractory AML (Acute Myeloid Leukemia) (Parts A and B) or relapsed or refractory high-risk MDS (Myelodysplastic Syndrome) (Part B only) as defined by World Health Organization criteria who are not suitable for other established therapies.
Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible
Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia) or acute leukemia of ambiguous lineage (ALUL), which includes mixed phenotype acute leukemia (MPAL); for patients with ALUL, the morphology and immunophenotype must be at least 50% B lymphoblastic
Patients with secondary B acute lymphoblastic leukemia (B-ALL) that developed after treatment of a prior malignancy with cytotoxic chemotherapy
Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (World Health Organization [WHO] criteria) are eligible; patients with Burkitt type ALL are NOT eligible
Patients with previously untreated acute lymphoblastic leukemia (B-cell or T-cell)
Philadelphia (Ph)-positive ALL, Burkitt’s leukemia/lymphoma, or lymphoblastic lymphoma
Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma as defined by the World Health Organization
Total bilirubin < 2 mg/dL (unless due to acute lymphoblastic leukemia [ALL])
Acute lymphoblastic leukemia (ALL):
Lymphoblastic lymphoma
Diagnosis of T-acute lymphoblastic leukemia/ lymphoblastic lymphoma according to World Health Organization (WHO) criteria which has relapsed or is refractory to chemotherapy
High grade lymphomas (Burkitts or lymphoblastic), plasma cell leukemia.
Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8)
Patients with lymphoblastic lymphoma are also eligible
Group A: CD19+ B-acute lymphoblastic leukemia (ALL) undergoing allogeneic HSCT or
Must have relapsed or refractory precursor B-cell acute lymphoblastic leukemia or acute lymphoblastic lymphoma
Patients with first relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)
Relapsed or refractory CD19-positive B-lineage acute lymphoblastic leukemia having received at least 1 prior line of therapy
Relapsed and/or refractory Philadelphia negative acute lymphoblastic leukemia or lymphoblastic lymphoma (Lead-in and Phase 2)
Relapsed and/or refractory Philadelphia positive acute lymphoblastic leukemia, Burkitt leukemia/lymphoma or “double-hit” leukemia/lymphoma (2 separate cohorts, phase II only)
PHASE I: Diagnosis of CD22-positive acute lymphoblastic leukemia
PHASE II: Diagnosis of CD22-positive acute lymphoblastic leukemia
Patients must have a confirmed diagnosis of either:\r\n* Acute lymphoblastic leukemia\r\n* Lymphoblastic lymphoma with detectable abnormal blasts in the bone marrow
Diagnosis of T acute lymphoblastic leukemia (T-ALL) or Burkitt’s leukemia/lymphoma
Patient with relapsed or refractory CD19 positive B-acute lymphoblastic leukaemia (B-ALL)
Patients with CLL, Burkitt or lymphoblastic lymphoma are excluded
Burkitt’s leukemia or lymphoma, T-cell ALL or lymphoblastic lymphoma
WHO classification defined B-lymphoid malignancy, with the exception of Burkitt lymphoma/leukemia, plasma cell myeloma, acute lymphoblastic leukemia, lymphoblastic lymphoma, and plasmablastic lymphoma.
Newly diagnosed acute lymphoblastic leukemia/lymphoma
Research participants with precursor B-cell acute lymphoblastic leukemia/lymphoma or plasma cell dyscrasias
Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma
Patients will be excluded if they have isolated extra-medullary relapse of acute lymphoblastic leukemia (ALL)
Ph-positive ALL, Burkitt’s leukemia or lymphoma, T-cell ALL or lymphoblastic lymphoma
Patients with acute lymphoblastic leukemia (ALL) or high grade (stage III or IV) non-Hodgkin lymphoma (NHL) after first relapse or with primary refractory disease
Documented acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) as defined by the criteria below:
Patients must have a confirmed diagnosis of either B- or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma that is either:\r\n* Arm A: Initially diagnosed at age 40 or later, OR\r\n* Arm B: Relapsed after or failed to respond to >= 1 previous chemotherapy regimen
Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease\r\n* NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
Confirmed diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma
Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
STRATUM III: \r\n* Any patients with MDD >= 1% and MRD positive (>= 0.01%) on day 8 in T-lymphoblastic lymphoma
EXCLUDING: Burkitt's lymphoma and precursor B lymphoblastic leukemia/lymphoma
Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma; acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute undifferentiated leukemia (AUL)
Patients of all ages with newly diagnosed, previously untreated CD-20+ acute lymphoblastic leukemia (ALL), or lymphoblastic lymphoma, Burkitt leukemia/lymphoma or having achieved complete remission (CR) with one course of induction chemotherapy
Previously untreated Philadelphia chromosome negative acute lymphoblastic leukemia/lymphoma
Participants must have relapsed or refractory acute lymphoblastic leukemia or lymphoma:\r\n* Stratum I: T-cell lymphoblastic leukemia or lymphoma in first relapse or refractory to one or two courses of frontline induction therapy\r\n* Stratum II: B-cell or T-cell lymphoblastic leukemia or lymphoma in second or third relapse or refractory to 2 or 3 induction or re-induction attempts; patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) must be refractory or relapsed after treatment with a regimen that included a tyrosine kinase inhibitor (TKI)
Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with ? 25% blasts in the bone marrow (M3), with or without extramedullary disease.
Patients must have precursor-B lymphoblastic leukemia or lymphoma
Acute Lymphoblastic Leukemia (ALL) in CR
NK cell lymphoblastic leukemia in any CR
Pathologically confirmed diagnosis of B-lineage acute lymphoblastic leukemia, Burkitt leukemia or lymphoma, or B-lineage lymphoblastic lymphoma
Survivor of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkins's lymphoma (NHL) (treated for ALL or NHL before the age of 21 years old and ?5 years post-treatment)
Burkitt and/or precursor lymphoblastic leukemia/lymphoma
Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission
Subjects with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma refractory to or relapsed from standard therapies
ALL or lymphoblastic lymphoma patients in first or higher relapse
Patients with biopsy-proven acute lymphoblastic leukemia, acute lymphoblastic lymphoma, or acute biphenotypic leukemia in remission or relapse
PARENT/CAREGIVER: Adult primary caregiver of children treated for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) or lymphoblastic lymphoma (LL) and daily contact with the child
Currently being treated in the maintenance phase of therapy for pediatric ALL or lymphoblastic lymphoma
Active relapse of ALL or lymphoblastic lymphoma
Currently enrolled on any therapeutic research study for the treatment of ALL or lymphoblastic lymphoma
Currently enrolled and receiving treatment for acute lymphoblastic leukemia (ALL) on the TOTXVI therapy protocol at St. Jude Children’s Research Hospital
Patients with:\r\n* Acute lymphoblastic leukemia/lymphoma \r\n* Malignant brain tumor \r\n* Non-central nervous system (CNS) solid tumors \r\n* Acute myeloblastic leukemia\r\n* Non-Hodgkin’s lymphoma \r\n* Hodgkin’s disease\r\n* Head and neck tumors
Acute lymphoblastic leukemia, including T lymphoblastic lymphoma with a history of marrow involvement
Acute lymphoblastic leukemia (ALL) in first or higher remission (< 5% blasts in the bone marrow)
Clinical Diagnosis of one of the following: Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Lymphoma
Acute lymphoblastic leukemia (ALL)