Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or as the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
STEP II: Patients must have complete induction without experiencing progression or patients must have received at least 6 cycles on Arm A and 4 cycles on Arm B but stopped induction therapy due to adverse events
REGISTRATION STEP 2-RANDOMIZATION: Patients must be deemed, in the judgment of the treating physician, to be ineligible for intensive induction therapy, or must have refused intensive induction therapy; rationale for clinical determination or notation of patient decision must be made
Patients must have resolved any serious infectious complications related to induction
DS HR B-ALL patients with Induction failure or BCR-ABL1
DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
Patient may be receiving or have completed induction therapy within 60 days prior to preregistration to step 0; no more than 300 days may have passed between the first day of induction therapy and preregistration to step 0\r\n* For patients who have completed induction therapy, restaging evaluation must show status of partial (PR) or complete response (CR); post-induction patients with evidence of clinical disease progression are not eligible for preregistration\r\n* Up to two regimens of chemotherapy are allowed as long as a continuous response was ongoing throughout therapy; overall, a partial response needs to have been achieved (using studies at the time of diagnosis as the baseline)\r\n**NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to rituximab(R)-cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens; however, R-CHOP alternating with R-dexamethasone, high-dose cytarabine, and cisplatin (DHAP) as a planned induction regimen would count as one regimen
Patients must have completed induction therapy within 120 days prior to registration to step 1, AND no more than 300 days may have elapsed from the first dose of induction chemotherapy (cycle 1 [C1] day 1 [D1]) given, until the last day of induction chemotherapy administered; for those assigned to Arms A, C, or D, the date of transplant (“day 0”) must not be greater than 365 days after the first dose of induction chemotherapy (C1D1) given\r\n* Patient must have received at least four (4) cycles of induction therapy \r\n* Up to two regimens of chemotherapy are allowed as long as a continuous response was ongoing throughout therapy\r\n** NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to R-CHOP (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens; however, R-CHOP alternating with R-DHAP as a planned induction regimen would count as one regimen
Patients must be registered within 35 days of administration of the last dose of first-line/induction systemic therapy.
Patient must have previously started induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
Patient has not received more than 14 days of multiagent induction therapy beginning with the first dose of vinCRIStine
Completion of remission induction therapy
Registration Step 1 – Induction/Re-Induction:
For patients 65-69 years of age, patient must be deemed not suitable for standard intensive induction chemotherapy at the discretion of the local investigator, or must have refused standard intensive chemotherapy
COHORT 1 PH-NEGATIVE PATIENTS ONLY: Patients must have achieved CR or CRi within 2 cycles of induction/re-induction with blinatumomab\r\n* NOTE: day 1 of post-remission = day 43 of the preceding cycle (+/- 3 days)
COHORT 2 PH-POSITIVE AND PH-LIKE DSMKF PATIENTS ONLY: Newly diagnosed Ph+, newly-diagnosed Ph-like DSMKF, and relapsed/refractory Ph+ patients without prior dasatinib or other 2nd or 3rd generation TKI therapy, must have achieved CR or CRi within 1 cycle of induction with dasatinib/prednisone, or within 2 cycles of re-induction with blinatumomab; relapsed/refractory Ph+ or Ph-like DSMKF patients with prior dasatinib or other 2nd or 3rd generation TKI therapy must have achieved CR or CRi within 2 cycles of re-induction therapy with blinatumomab\r\n* NOTE: day 1 of post-remission = day 85 of the preceding induction cycle (+/- 3 days), or day 43 of the preceding re-induction cycle (+/- 3 days) as applicable
Eligible for standard induction chemotherapy according to their treating physician
Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
leukemia refractory to ? 2 induction attempts,
Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine
Treatment-naive participants unfit for induction chemotherapy for AML due to comorbidities who are >/=65 years old
1. Written informed consent must be obtained prior to any screening procedures\n\n          2. Male or female patients ? 18 years of age who present with one of the following:\n\n             Arms 1-3:\n\n               -  Refractory/relapsed AML following ?1 prior therapies and are deemed by the\n                  investigator not to be candidates for standard therapy, including re-induction\n                  with cytarabine or other established chemotherapy regimens for patients with AML\n                  (patients who are suitable for standard re-induction chemotherapy or\n                  hematopoietic stem cell transplantation and willing to receive it are excluded)\n\n               -  De novo AML patients who are suitable for treatment with decitabine (patients who\n                  are suitable for standard induction chemotherapy or hematopoietic stem cell\n                  transplantation and willing to receive it are excluded)\n\n               -  High risk MDS (patients who are suitable for standard re-induction chemotherapy\n                  or hematopoietic stem cell transplantation and willing to receive it are\n                  excluded)\n\n             Arms 4-5:\n\n               -  Refractory / relapsed AML following ?1 prior therapies (Arms 4a & 5a)\n\n               -  High risk MDS who have failed hypomethylating agent therapy (Arms 4b & 5b) (Note:\n                  hypomethylating agent failure is defined as progressive disease on\n                  hypomethylating agent therapy or lack of clinically meaningful response as deemed\n                  by investigator after at least 4 cycles of hypomethylating agent therapy.)\n\n          3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ? 2\n\n          4. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to\n             the institutions guidelines and be willing to undergo a bone marrow aspirate\n             and/biopsy at screening, during and at the end of therapy on this study. Exceptions\n             may be considered after documented discussion with Novartis.\n\n          5. Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by\n             the investigator and as per local decitabine package insert.
COHORT 2: Is eligible for treatment with a standard cytarabine and anthracycline or similar intensive induction chemotherapy, or is willing to receive intensive induction therapy; if subject is not considered eligible for treatment with standard or similar intensive induction chemotherapy due to comorbidities or other factors, or is unwilling to receive intensive induction therapy will be allowed to participate in this study
Patients must be within 12 months of initiation of induction therapy and must have had not more than 2 prior induction regimens
Patients with AML refractory to primary induction chemotherapy, relapsed disease, or age >= 60 and not appropriate for standard cytotoxic therapy due to age, performance status, and/or adverse risk factors according to the treating physician
Previous treatment for MDS or AML with intensive chemotherapy regimen (induction chemotherapy) or hypomethylating agent
Acute myeloid leukemia\r\n* MRD > 5% at day 22 induction 1\r\n* MRD > 0.1% after induction 2\r\n* FMS-like tyrosine kinase (FLT)/internal tandem duplication (ITD) with allelic ratio > 0.4 and MRD > 0.1% at day 29 induction 1\r\n* Translocation (6:9), (8:6), (16:21), monosomy7, monosomy 5, 5q.\r\n* M7 without translocation (1;22)\r\n* M7 with KMT2A rearrangements, inv(16)(p13.3q24.3) [CBFA2T3-GLIS2] or t(11;12)(p15;p13) [NUP98-KDM5A]\r\n* AML in 2nd or subsequent CR\r\n* Therapy related or secondary AML\r\n* Refractory anemia with excess blasts (RAEB) 2
Participants must have pathologically confirmed relapsed or refractory acute myeloid leukemia following International Working Group (IWG) criteria\r\n* For subjects with relapsed AML: evidence of >= 5% blasts in the bone marrow or >= 5% blasts in peripheral blood or the development of extramedullary disease who relapse after:\r\n** Allogeneic hematopoietic stem cell transplant, or\r\n** A minimum of one cycle of standard cytotoxic chemotherapy or two cycles of any hypomethylating agent-based therapy\r\n* For subjects with refractory AML: a minimum of 2 prior induction regimens (example: patients who receive 7+3 followed by 5+2 would count as one induction regimen) or a minimum of two cycles of any hypomethylating agent-based therapy
Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside plus 2-3 days of an anthracycline, or high-dose cytarabine
Participant has not received more than 2 cycles of induction chemotherapy to achieve CR1. The induction cycles can be the same regimen or different regimens. The regimen(s) may contain conventional agents, investigational agents, or a combination of both.
Induction chemotherapy was administered with any combination of the following agents:
Patients may receive hydroxyurea or leukopheresis as necessary; hydroxyurea can be continued through induction, as determined by the treating investigator; patients who require hydroxyurea after the 2 induction cycles will be off study
Participants with leukemia must meet one of the following:\r\n* In first hematologic relapse, OR\r\n* Refractory to one or two courses of frontline induction therapy (>= 5% blasts in the bone marrow or peripheral blood confirmed by flow cytometric analysis)\r\n* Note: participants aged 1 to 5 years with induction failure and favorable cytogenetics (i.e., hyperdiploid or human ets variant 6 [ETV6]-runt-related transcription factor 1 [RUNX1]) will not be eligible for this protocol; other patients younger than 6 years will be eligible
AUTOLOGOUS APHERESIS: CD19+ ALL with any of the following:\r\n* Minimal residual disease (MRD) >= 1% at end of up-front induction therapy\r\n* Hypodiploid (< 44 chromosomes or < 0.95 deoxyribonucleic acid [DNA] index) CD19+ ALL with detectable disease at the end of up-front induction therapy \r\n* Increase in disease burden any time after the completion of up-front induction therapy\r\n* Primary refractory disease despite 2 cycles of an intensive chemotherapy regimen designed to induce remission\r\n* Refractory disease despite salvage therapy\r\n* 1st or greater relapse\r\n* Note: if patient meets CD19+ ALL disease criteria, subsequent receipt of cancer directed therapy that eradicates disease does not preclude them from proceeding with this study
ALL patient refractory to their first induction only or their first relapse, will be excluded; they must be refractory to at least one salvage therapy, or relapse after first salvage, to be eligible
Failure to one induction course of chemotherapy (these patients will be analyzed separately)
The time from the end of last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days
Patients who have been treated with chemotherapy or radiation for the purpose of induction, re-induction or consolidation, within two weeks of planned study enrollment
Any subject who is a candidate for intensive induction therapy and agrees to receive this therapy
Meet any criteria necessary for the safe and proper use of the induction and consolidation agents involved in this trial
Subjects unable or unwilling to have their first randomized treatment within three weeks of the post induction imaging and within five weeks of their last induction treatment
Patients must have a history of tumor progression or relapse or failure to achieve complete response following standard high-dose induction chemotherapy
Not considered eligible for any of the chemotherapy agents included in the induction regimen
Patients who have received induction chemotherapy for their cancer diagnosis.
Patients eligible for intensive induction chemotherapy and “medically unfit” based on a treatment related mortality (TRM) score >= 13.1\r\n* TRM score= a scoring model which predicts early death following intensive induction chemotherapy in newly diagnosed AML; \r\n** Model looks at ECOG performance status (PS), age, platelet count, albumin, second (2nd) AML, white blood cells (WBC), percentage (%) peripheral blasts, creatinine\r\n** Score above 13.1 associated with 31%+ chance of death after induction
Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:\r\n* Primary induction failure:\r\n** De Novo AML: No CR after 2, 3 or 4 induction attempts with high dose chemotherapy\r\n** Secondary AML (from myelodysplastic syndrome [MDS] or treatment related): No CR after 1, 2 or 3 cycles of high dose chemotherapy\r\n* Relapsed:\r\n** Not in CR after 1 or 2 cycles of standard re-induction therapy\r\n*** For patients > 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required
Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:\r\n* Primary induction failure:\r\n** De novo - no CR after 2 or more induction attempts with high dose chemotherapy\r\n** Secondary AML (from myelodysplastic syndrome [MDS] or treatment related): no CR after 1 or more cycles of high dose chemotherapy\r\n** Note: hypomethylating agents such as azacitidine will count as induction failure\r\n* Relapsed: not in CR after 1 or more cycles of standard re-induction therapy - patients > 60 years of age, the 1 cycle of standard chemotherapy is not required\r\n* Relapsed > 18 months after transplant: no re-induction required and no more than 1 re-induction cycle is allowed
Patients must be either refractory to or relapsed after only induction therapy; patients who do not achieve CR after induction therapy are considered primary refractory and are allowed to enter study
Patients will have received at least 2 cycles of induction chemotherapy with pemetrexed/cisplatin or pemetrexed/carboplatin
Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one cycle of re-induction therapy; standard dose 10-day decitabine (20 mg/m^2 daily IV x 10 days) or 7-day azacitidine (75-100 mg/m^2 daily SC/IV x 7 days) will be considered as one cycle of induction therapy
Has undergone cytotoxic induction therapy
Relapsed or refractory high-grade myeloid neoplasms, defined as having a blast count of >= 10% blasts at initial diagnosis; examples include excess blasts (EB)-2, with >= 10% blasts at initial diagnosis, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML-2); standard definitions of relapse will apply (i.e., characterized by >= 5% abnormal blasts as assessed by multiparameter flow cytometry or morphologic examination; peripheral blood blasts; or extramedullary granulocytic sarcoma, per European LeukemiaNet [ELN] 2017 guidelines); bone marrow aspirate/biopsy will be accepted if performed outside University of Washington/Fred Hutchinson Cancer Research Center (UW/FHCRC); determination of disease status should occur within 30 days of signing informed consent\r\n* R/R high-grade myeloid neoplasm following intensive induction chemotherapy; relapsed high-grade myeloid neoplasm: patients will be classified as relapsed if they have >= 5% blasts after being in a complete remission (CR) following treatment for high-grade myeloid neoplasm; refractory high-grade myeloid neoplasm: patients may be classified as refractory if they have received at least one prior cycle of induction chemotherapy, whether with cladribine cytarabine mitoxantrone (GCLAM) or another regimen\r\n** Patients may have received up to two courses of intensive induction chemotherapy during initial treatment prior to enrollment on this protocol; for example, patients who have received two courses of granulocyte colony stimulating factor (G-CSF) GCLAM (or similar) chemotherapy, with most recent high-dose cytarabine-containing chemotherapy > 6 months ago and CR lasting > 6 months, will be eligible for this protocol; regimens “similar to GCLAM” would include cytarabine at doses of 1g/m^2 for at least 5 doses; examples of regimens “similar to GCLAM” would be GCLA, fludarabine cytarabine granulocyte (FLAG), and FLAG-idarubicin (ida); however, patients who received more than two courses of GCLAM (or similar) chemotherapy, or patients who received two courses of GCLAM and had CR lasting < 6 months, would not be eligible\r\n* R/R high-grade myeloid neoplasm following less intensive induction chemotherapy. Patients who have received at least three cycles of treatment with a hypomethylating agent (HMA; such as azacitidine or decitabine) and still have >= 10% blasts will be eligible for the study (they will be considered refractory); similarly, patients who have received three or more cycles of HMA therapy who have had a response (e.g., achieving CR with < 5% blasts), but who then progress using standard definitions of relapse, will also be eligible (they will be considered relapsed)
More than two prior courses of induction chemotherapy
Have received the last dose of induction or consolidation chemotherapy within 3 months of enrollment
Patient must have completed a frontline induction therapy (minimum of 2 treatment cycles); NOTE: Standard therapies/therapeutic agents are defined as those listed in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of CLL; also, patients who received induction regimen as part of a clinical trial and is not necessarily mentioned in the NCCN guidelines, will also be eligible as long as the patient has completed at least 2 treatment cycles of induction regimen, achieved a clinical response (PR or CR) and is able to meet all other criteria for the study; however, patients who have previously received ibrutinib or have been randomized to ibrutinib containing arms in a clinical trial will not be eligible for this study
Have received induction chemotherapy and at least one cycle of consolidation chemotherapy; patients should have achieved a CR within 12 months of enrollment onto protocol
Patients with diagnosis of AML, judged primary refractory after up to 2 courses of AML induction with therapy (> 5% blasts on day 21 [+/-7 days] bone marrow aspirate and/or biopsy from the beginning of induction chemotherapy, up to 42 days)
Prior induction therapy with decitabine, clofarabine, idarubicin (DAC) + cytarabine (CIA)
Patients must meet one of the following criteria:\r\n* The presence of refractory or progressive disease (PD) prior to or following completion of standard therapy for MIBG avid tumors\r\n* For patients with neuroblastoma, the presence of mixed response (MR), or no response (NR) following the completion of A3973 or equivalent induction therapy, or the presence of a partial response (PR) with high Curie score (> 2) following induction therapy \r\n* Patients with de novo high risk neuroblastoma who have completed standard induction therapy and do not achieve a complete response (CR), very good partial response (VGPR), or PR with low Curie score post induction are eligible; for patients with neuroblastoma the revised International Neuroblastoma Response Criteria (INRC) shall be used to assess pre-treatment disease status
Recipients with acute lymphoblastic leukemia (ALL) in CR1 must have one of the following:\r\n* Adverse cytogenetics defined as translocations involving t(4;11), t(1;19), t(8;14), 11q23, t(9;22) or bcr-abl rearrangement or complex cytogenetic abnormalities\r\n* Presence of minimal residual disease using multicolor flow cytometry or other analytic technique after primary induction chemotherapy\r\n* Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy
Patients in their FIRST CR or CRi may be eligible for enrollment only if they have a high risk feature, including, but not limited to: adverse karyotype, fms-related tyrosine kinase 3 (FLT3) mutation, history of antecedent hematologic disorder (AHD), presence of dysplasia in the bone marrow, therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, or presence of persistent minimal residual disease (detected by cytogenetics, molecular markers, or flow cytometry) at any point after initial induction cycle; patients aged >= 18 years with AML who have achieved a SECOND CR or CRi within 12 months of enrollment and are not immediately candidates for allogeneic stem cell transplant are also eligible
Patients should have received induction chemotherapy for AML and at least 1 consolidation
Prior induction therapy had to include no more than two cycles of cytotoxic chemotherapy and at least one induction cycle must have consisted of an anthracycline or anthracenedione and cytarabine combination with a reasonable schedule/dose according to the discretion of the investigator
More than 2 cycles of prior induction therapy for AML
The time from the end last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days from planned start of study treatment; Note: Chemotherapy given within 14 days of planned study enrollment for the purpose of controlling counts is permitted
DIAGNOSIS REQUIREMENT FOR PHASE I PATIENTS: Refractory AML without complete remission (CR) after induction therapy (primary induction failure) or relapsed AML after obtaining a CR OR
Measurable disease prior to induction chemotherapy
Cohort B: patients who have received prior fludarabine , clofarabine or drugs known to target T cells not permitted; but prior standard induction with anthracyclines and cytarabine ALLOWED including after demethylating agents
Prior receipt of induction chemotherapy followed by referral for concurrent chemoradiation is allowed
Patients must have either (1) refractory or relapsed high-risk NB (including v-myc myelocytomatosis viral related oncogene [MYCN]-amplified stage 3/4/4S and MYCN-nonamplified stage 4 in patients greater than 18 months of age) resistant to standard therapy, or (2) refractory or relapsed GD2-positive tumor after receiving available life-prolonging therapies\r\n* For NB, standard therapy generally includes 5-8 cycles of high dose induction chemotherapy followed by resection of gross residual tumor, then usually myeloablative chemotherapy with peripheral blood stem cell rescue and radiation therapy to the primary site; there are also salvage chemotherapy regimens for residual disease after standard induction therapy or for relapsed NB; some examples of these chemotherapy combinations are: high-dose cyclophosphamide, topotecan and vincristine; high-dose cyclophosphamide, irinotecan and vincristine; irinotecan and temozolomide; or ifosfamide, carboplatin and etoposide
Subjects with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT.
Be in first relapse (within 24 months of CR) or have primary refractory AML (refractory to initial induction therapy using 1 or 2 cycles of intensive anthracycline/cytarabine ± etoposide or cladribine induction) or have newly diagnosed high-risk AML as defined in this protocol.
Group A : Individuals > 18 years of age with previously untreated AML who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician
CR or PR required; remission status will be assessed at the completion of induction chemotherapy and prior to enrollment on protocol
Up to one cycle of prior induction therapy will be permitted to include patients in whom presence of \good-risk\ cytogenetics was initially missed; if the patient is in remission from induction therapy, he/she will receive post-remission therapy; if the patient is not in remission then he/she will receive induction therapy
At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy or azacitidine or decitabine or tyrosine kinase inhibitor
Refractory leukemia or MDS; these patients may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody; these high risk patients will be analyzed separately (Arm 3)
B-cell cohort: Stage 1; ALL in second or greater relapse or refractory to 2 prior induction regimens with greater than or equal to (>=) 5 percent (%) blasts in the bone marrow and aged 1 to less than (<) 18 years. Stage 2; ALL in second or greater relapse or refractory to 2 prior induction regimens with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in second or greater relapse or refractory to 2 prior induction regimens and biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years.
T-cell cohort: Stage 1; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to <18 years. Stage 2; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in first relapse or refractory to 1 prior induction/consolidation regimen biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years
Inclusion Criteria:\n\n        2.3.1 Inclusion Criteria for the Biology (KIR2DL1 Polymorphisms/ALL MRD), Comparative\n        Outcomes, and Cost Effectiveness Trial\n\n          1. Any patient with ALL, AML, or MDS who is deemed eligible for and undergoes HCT at\n             participating centers who provides consent for the KIR2DL1 polymorphisms, comparative\n             outcomes and cost-effectiveness portion of the trial.\n\n          2. Any ALL patient undergoing allogeneic HCT at participating centers is eligible for the\n             ALL deep sequence MRD portion of the trial.\n\n          3. Patients ineligible for the KIR-favorable haploidentical phase II trial who require\n             T-cell depletion may be treated using TCR ??+CD3+/CD19+ cell depletion. These patients\n             will be followed descriptively on this portion of the trial. Preparative regimen will\n             be at the discretion of the transplant center, but the options associated with this\n             protocol are recommended.\n\n        2.3.2 Inclusion Criteria for the KIR-favorable Haploidentical Phase II trial:\n\n          1. Age < 22 years\n\n          2. Disease and disease status:\n\n               -  ALL high-risk in first remission (<5% blasts by morphology pre-transplant)\n                  meeting criteria for transplant. Example CR1 indications: induction failure (>5%\n                  blasts by morphology on post-induction BM), minimal residual disease greater than\n                  or equal to 1% marrow blasts by morphology after induction, minimal residual\n                  disease by flow cytometry >0.01% after consolidation, hypodiploidy (<44\n                  chromosomes), persistent or recurrent cytogenetic or molecular evidence of\n                  disease during therapy requiring additional therapy after induction to achieve\n                  remission (e.g. persistent molecular BCR-ABL positivity).\n\n               -  ALL in second remission: B-cell; early (less than or equal to 36 months from\n                  initiation of therapy) BM relapse, late BM relapse with MRD >0.1% by flow\n                  cytometry after first induction therapy; T-cell or Ph+ with BM relapse at any\n                  time; very early (less than 18 months from initiation of therapy) isolated\n                  extramedullary relapse (T or B-cell)\n\n               -  Myelodysplastic syndrome (MDS): Any 2001 WHO classification subtype (Appendix I).\n                  RAEB-2 patients may proceed directly to transplant, but may also receive\n                  induction chemotherapy before transplant. Patients with ?20% morphologic marrow\n                  blasts will require induction therapy to reduce morphologic marrow blasts below\n                  5% before transplant.\n\n               -  High-risk AML defined as monosomy 5, del 5q, monosomy 7, M6, M7, t(6;9),\n                  FLT3-ITD, or patients who have greater than or equal to 25% blasts by morphology\n                  after induction, or who do not achieve CR after 2 courses of therapy. Also,\n                  patients with ? 0.1% MRD or evidence of progressive extramedullary disease after\n                  induction chemotherapy.\n\n               -  AML in second or subsequent morphologic remission.\n\n          3. Has not received a prior allogeneic hematopoietic stem cell transplant.\n\n          4. Does not have a suitable HLA-matched sibling donor available for stem cell donation.\n\n          5. Does not have a suitable matched or single antigen mismatched related or unrelated\n             donor available at any time (noted by search), or it is in the patient's best interest\n             as judged by the attending to move forward with stem cell transplantation rather than\n             wait for an unrelated donor to become available (refer to subsection 2.5.1 for further\n             details).\n\n          6. Has a suitable HLA KIR favorable haploidentical matched family member available for\n             stem cell donation.\n\n          7. Karnofsky Index or Lansky Play-Performance Scale ? 60 % on pre-transplant evaluation.\n             Karnofsky scores must be used for patients > 16 years of age and Lansky scores for\n             patients < 16 years of age.\n\n          8. Able to give informed consent if > 18 years, or with a legal guardian capable of\n             giving informed consent if < 18 years.\n\n          9. Adequate organ function (within 4 weeks of initiation of preparative regimen), defined\n             as:\n\n               -  Pulmonary: FEV1, FVC, and corrected DLCO must all be ? 50% of predicted by\n                  pulmonary function tests (PFTs). For children who are unable to perform for PFTs\n                  due to age, the criteria are: no evidence of dyspnea at rest and no need for\n                  supplemental oxygen.\n\n               -  Renal: Creatinine clearance or radioisotope GFR ³ 70 mL/min/1.73 m2 or a serum\n                  creatinine based on age/gender as follows:\n\n        Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8\n        0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4\n\n        ? 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the\n        Schwartz formula for estimating GFR utilizing child length and stature data published by\n        the CDC.45\n\n          -  Cardiac: Shortening fraction of ? 27% by echocardiogram or radionuclide scan (MUGA) or\n             ejection fraction of ? 50% by echocardiogram or radionuclide scan (MUGA), choice of\n             test according to local standard of care.\n\n          -  Hepatic: \\SGOT (AST) or SGPT (ALT) < 5 x upper limit of normal (ULN) for age.\n             Conjugated bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome.\n\n        Exclusion Criteria:\n\n          1. Pregnant or lactating females are ineligible as many of the medications used in this\n             protocol could be harmful to unborn children and infants.\n\n          2. Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded.\n             Patients with history of fungal disease during induction therapy may proceed if they\n             have a significant response to antifungal therapy with no or minimal evidence of\n             disease remaining by CT evaluation.\n\n          3. Patients with active CNS leukemia or any other active site of extramedullary disease\n             at the time of enrollment are not permitted. Note: Those with prior history of CNS or\n             extramedullary disease, but with no active disease at the time of pre-transplant\n             workup, are eligible.\n\n          4. Patients with genetic disorders (generally marrow failure syndromes) prone to\n             secondary AML/ALL with known poor outcome are not eligible (Fanconi Anemia, Kostmann\n             Syndrome, Dyskeratosis Congenita, etc).
ECOG performance status within 48 hours prior to induction chemotherapy ? 3
Must be within 3 months from the last induction regimen at the time of starting cytarabine chemotherapy in this protocol
In Cohorts A3 and A4 only, participants with AML eligible for standard intensive induction therapy with an anthracycline and cytarabine
Patients must be > 28 days from the start of induction or re-induction chemotherapy, or from the start of consolidation cycle 1 (if received) and < 90 days following recovery from most recent treatment; and they must have achieved and maintained a response to induction therapy (CR, CRi, or “morphologic disease-free state”)
Patients must have recovered from the effects of induction, re-induction, or consolidation chemotherapy (all toxicities =< grade I with the exception of reversible electrolyte abnormalities), and have no ongoing active infection requiring treatment
Patient with and without Down syndrome are eligible and must have one of the following:\r\n* Second or greater relapse;\r\n* Primary refractory disease with at least 2 prior induction attempts;\r\n* First relapse refractory to at least one prior re-induction attempt\r\n* Any relapse after HSCT\r\n* First relapse with no prior re-induction attempt in setting of Down syndrome\r\n* Note: Patients with Down syndrome are eligible with any disease status including first relapse with no prior re-induction attempt; patients without Down syndrome are NOT eligible if in first relapse with no prior re-induction attempt
Refractory to at least 1 cycle of induction chemotherapy
Patients with untreated AML who are either unwilling or unable to undergo high-dose induction/consolidation intensive chemotherapy
Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:\r\n* Non-M3 AML refractory to standard primary induction therapy \r\n* Non-M3 AML relapsed after (i) any standard induction therapy (ii) any number of standard or experimental salvage therapies\r\n* Newly diagnosed non-M3 AML not eligible for intensive induction chemotherapy
Subjects who are suitable for and willing to receive standard intensive induction therapy
To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016) \r\n* Relapsed patients\r\n** Patients must be in first relapse, and\r\n** Patients must not have received prior re-induction therapy\r\n* Refractory patients\r\n** Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example\r\n* Treatment-related AML (t-AML)\r\n** Patients must be previously untreated for secondary AML
To be eligible for the phase 2 efficacy phase:\r\n* Relapse patients:\r\n** Patients must be in first marrow relapse, and \r\n** Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody
Meets ONE of the following disease criteria:\r\n* Primary (de novo) AML induction failure: no CR after 2 or more induction attempts with high dose chemotherapy (note: hypomethylating agents such as azacitidine will count as induction failure)\r\n* Relapsed AML or secondary AML (from myelodysplastic syndrome [MDS] or treatment related): not in CR after 1 or more cycles of standard re-induction therapy\r\n** For patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:\r\n*** Relapse within 6 months of last chemotherapy\r\n*** Bone marrow (BM) blast count < 30% within 10 days of starting protocol therapy\r\n* AML relapsed > 4 months after transplant: no re-induction required, and no more than 1 re-induction cycle is allowed\r\n* Use of hydroxyurea is permitted to control blasts counts\r\n* Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to enrollment; CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment
ALL or AML patients who received chemotherapy (induction or consolidation) can proceed to transplant once bone marrow cellularity is > 10 % with no evidence of leukemia
Please note: prior intensive induction therapy for acute leukemia is allowed only in the phase I portion of this study\r\n* PHASE I PORTION ONLY: Patients of any age who have received no more than one prior attempt at induction chemotherapy (and may have received treatment consolidation), must have recovered from acute toxicities of therapy and be >= 4 weeks from last dose of cytotoxic treatment; patients who have received prior autologous or allogeneic stem cell transplantation are not eligible; patients may have received 1 or 2 cycles of cytarabine-based therapy as attempted induction
Phase II portion: Patients must have not received any prior intensive induction therapy for AML\r\n* Intensive induction includes standard induction chemotherapy such as 7 & 3, high dose cytarabine, mitoxantrone-etoposide, low-dose subcutaneous cytarabine\r\n* Allowed \non-intensive\ prior treatments for pre-existing hematologic conditions (i.e., MDS, chronic myelomonocytic leukemia [CMML]) will include: hydroxyurea, thalidomide, hematopoietic growth factors, Zarnestra, Lenalidomide, arsenic, Imatinib, and corticosteroids, suberoylanilide hydroxamic acid [SAHA] inhibitors; hydroxyurea is allowed up to 24 hours before initiating treatment and to control blood counts during the first cycle of chemotherapy after azacitidine has completed; a minimum of 4 weeks must have elapsed since the administration of thalidomide, Zarnestra, Revlimid, arsenic, SAHA inhibitors, or any investigational medication; a minimum of five days must have elapsed since the administration of growth factors
Subject has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation, and/or maintenance).
In first relapse (with duration of remission of 6 months or less) or refractory after prior therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone-containing induction block at a standard dose.
The previous induction regimen may have been a SCT with intent to induce a CR.
The previous induction regimen may have been a SCT with intent to induce a CR.
INDUCTION ELIGIBILITY:
Patients must be registered to Consolidation therapy within 60 days of beginning Induction therapy (with day 1 being the start of Induction)
Patients must be in morphologic complete response (CR), complete response with incomplete hematologic recovery (CRi), partial response (PR) by international working group criteria post induction therapy, or patients refractory to induction therapy provided they have < 1000 peripheral blasts/mm^3 and white blood cells (WBC) =< 10 x 10^9/L; patients in PR and/or those who are refractory and who have undergone only one course of induction therapy will be eligible only if one or more of the following criteria are met:\r\n* Patient preference to forgo further induction therapy in favor of low or intermediate-intensity therapy\r\n* Patients are deemed unlikely to benefit from anthracycline cytarabine induction therapies for any of the following reasons:\r\n** Therapy-related AML\r\n** Prior myelodysplastic syndrome or myeloproliferative neoplasm\r\n** The presence of cytogenetic or molecular genetic features place patient in the Intermediate-I, Intermediate-II or adverse genetic group as defined by the European LeukemiaNet\r\n* Patients who have experienced one or more Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 grade 3-4 treatment related non-hematologic toxicity within 30 days of beginning the first course of induction therapy
Previous administration of > 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
Tumor progression during or immediately after completion of =< 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease
Patients must have primary refractory ALL based on failure to achieve a hematologic or molecular remission after induction therapy with dasatinib and steroids or dasatinib and chemotherapy, or have relapsed after treatment with a tyrosine kinase inhibitor with or without chemotherapy\r\n* Note: Prior course of dasatinib and steroid induction therapy should have included dasatinib 140mg PO daily on days 1-84 and prednisone 60mg/m^2 (capped at 120mg, or equivalent steroid dose) on days 1-28; if patients were unable to tolerate full steroid dose during induction therapy they will still be eligible\r\n* Note: Patients with refractory or relapsed disease in the central nervous system will be eligible
Unfit for chemotherapy based on investigator assessment or patient not willing to receive intensive induction as advised by investigator
Any cancer directed therapies between completion of induction chemotherapy and treatment on protocol
Patients who have received induction chemotherapy for their cancer diagnosis
No induction chemotherapy
Subject must have histological confirmation of AML and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
Underwent standard of care induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial.
Cytoreduction allowed: \r\n* Hydroxyurea, corticosteroids, leukapheresis can be used prior to start of induction chemotherapy\r\n* Cyclophosphamide up to dose 50-60 mg/kg is allowed for cytoreduction, but must be given at least 7+/- 2 days before start of induction chemotherapy
Patients who have had conventional intensive cytotoxic induction chemotherapy for treatment of specifically MDS or AML are excluded
Failing to achieve a CR from original diagnosis after at least 1 induction attempt
Completion of induction chemotherapy with a minimum of 4 and no more than 6 cycles of a platinum agent and etoposide within 8 weeks of trial initiation.
Phase 2: i. Participants with AML who are refractory to, or have relapsed after, initial treatment for their disease, with no more than one prior line of therapy, and are judged not to be candidates for re-induction therapy that includes hematopoietic cell transplantation. Participants who have received prior cytarabine or decitabine are not excluded. OR ii. Participants with newly diagnosed, untreated AML ineligible for, or who have refused, standard intensive induction therapy
Subjects who are refractory to initial induction or re-induction treatment
Subjects must have exhibited lack of CR or PR or progression within 6 months after the last dose of a chemotherapy induction regimen or RIT.
Re-Induction Criteria (if applicable):
Patients who have progressed on initial therapy will not be considered for re-induction treatment
Patients must demonstrate one of the following:\r\n* Relapse after first complete remission\r\n* Refractory to induction chemotherapy (for example, failure to respond to 1 or more cycles of daunorubicin and cytarabine) or to reinduction\r\n* Refractory to hypomethylating agents
Not considered eligible for one or more of the chemotherapy agents included in the induction regimen
Primary AML induction failure: no complete remission (CR) after 2 or more induction attempts
Acute myeloid leukemia (AML) fitting within one of the following disease groups:\r\n* Primary induction failure (PIF): patients who have not achieved a complete remission (CR) after two induction cycles of cytotoxic therapy (i.e. 7+3, mitoxantrone, etoposide, and cytarabine [MEC], fludarabine, cytarabine, and granulocyte-colony stimulating factor [FLAG], etc.) and having =< 10,000 absolute circulating blasts measured at least 21 days from prior therapy; hydroxyurea may be used to control blasts count; demethylating agents do not count as induction therapy; however early re-induction therapy based on residual disease on a day 14 bone marrow (BM) will count as a 2nd cycle\r\n* Relapsed disease with low disease burden: AML with =< 10,000 absolute circulating blasts; hydroxyurea may be used to control blasts count: no re-induction attempts are required, but a maximum of 2 re-induction attempts is allowed to be eligible\r\n* CR3 or greater: this will include CRp defined as CR without platelet recovery to 100,000/mcL\r\n* CR1 or CR2 with high risk features: includes therapy induced, prior myelodysplastic syndromes (MDS) or myeloproliferative disease (MPD), high risk cytogenetic or molecular phenotype with no available donor (sibling or unrelated adult)
Failure to one induction course of chemotherapy (these patients will be analyzed separately)
Patients must be within 30 days of completing induction therapy.
Able to receive intensive induction chemotherapy
Patients who have received induction chemotherapy before radiation treatment
Induction chemotherapy is allowed
Recipients with ALL in CR1 must have one of the following:\r\n* Adverse cytogenetics or residual disease detectable by flow cytometry, cytogenetic analysis, FISH, or PCR; adverse cytogenetics in ALL are defined as translocations involving t(4;11), t(1;19), t(8;14), 11q23, t(9;22) or bcr-abl rearrangement or complex cytogenetic abnormalities\r\n* Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy
Refractory disease after first or greater relapse and a re-induction attempt, OR
Failing to go into remission from original diagnosis after 2 previous induction attempts.
Patients with will be eligible if they are either in partial response, or have stable disease after no more than two attempts of induction therapy
Patients must have stable disease (or better) during the initial induction chemotherapy with first-line chemotherapy
Patient must start maintenance therapy at least 14 days after the last administered induction chemotherapy but no later than 30 days
Two or more relapses after initial response to induction chemotherapy
Patients should have received at least 2 cycles of induction therapy or 1 induction and 1 consolidation cycle, OR patient should be considered to have completed all planned chemotherapy, OR patient is considered to be unable, unfit or unwilling to receive additional chemotherapy
Previous treatment with hypomethylating agent or induction chemotherapy for MDS
Ability to undergo standard induction chemotherapy
Anti-neoplastic treatment less than 14 days prior to enrollment, with the exceptions of hydroxyurea or, in the case of a patient with primary refractory AML, prior induction chemotherapy
Patients who are not eligible for standard induction chemotherapy (or any standard therapy known to be life prolonging) because of poor performance status, significant tissue comorbidities, or unfavorable risk of disease
Patients eligible include those with diagnosis of AML other than acute promyelocytic leukemia by World Health Organization (WHO) criteria with relapsed disease after induction therapy or refractory to induction chemotherapy, as determined by morphology on bone marrow biopsy; also eligible are patients unwilling to receive standard induction chemotherapy
AML patients must either:\r\n* Be ineligible to receive standard intensive induction chemotherapy (based upon judgement of the treating physician, based on parameters such as comorbidities, cytogenetic studies as well as), or\r\n* Have relapsed or refractory disease to previous chemotherapy (induction and/or consolidation) for acute myeloid leukemia; patients must have recovered from acute toxicities of AML chemotherapy
INDUCTION CHEMOTHERAPY:
Patient must be sufficiently recovered from any adverse effect of induction chemotherapy as determined by treating investigator; the duration of this recovery period is anticipated to be 1-3 weeks
Patients with plasma cell myeloma treated with induction therapy or re-induction therapy, who at the time of study enrollment have documented evidence of stable disease response or better according to International Myeloma Workshop Consensus Panel
Chemotherapy refractory acute leukemia (AL) will be defined by not in achieving a hematological remission after two consecutive standard courses of induction therapy
AML relapsed or refractory to at least one attempt at induction or subjects not candidates for aggressive induction regimens
Patients younger than 50 years old, after first induction of chemotherapy, who are able to safely tolerate re-induction therapy with high dose chemotherapy are not eligible for this study (patients who are 50 years old or older or patients younger than 50 who are not able to tolerate an aggressive reinduction chemotherapy, based on the physician assessment, are still be eligible for this study if they fail their first induction)
Patients with AML must have had at least 2 prior therapeutic attempts including frontline induction.
Patients with ALL must have had at least 3 prior therapeutic attempts including frontline induction.
Subjects who are refractory* or who have relapsed** following first line AML therapy with cytarabine/anthracycline based chemotherapy, with or without a tyrosine kinase inhibitor. *Refractory to induction therapy is defined as never achieving CR, CRi or CRp (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI. or **First relapse is defined as untreated hematologic relapse (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI that induced a CR/CRi/CRp. Subjects are allowed to receive induction, consolidation, transplant and/or maintenance prior to achieving their first CR/CRi/CRp.
Patients with relapsed or refractory AML; patients must have failed at least one prior induction regimen for AML; the maximum number of prior lines of induction is 3
Patients must have at least received an appropriate induction therapy regimen. Patients with persistent leukemia after induction therapy, or with recurrence of leukemia at any time during the course of treatment (including allogeneic HSCT) are eligible;
Refractory to at least 1 cycle of induction chemotherapy
Platelets >= 100,000/mm^3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
Either achieved complete remission (greater than 12 weeks in duration) with initial induction/consolidation and have experienced relapse of disease or declined treatment with high-dose induction/consolidation
Eligible for induction by daunorubicin + cytarabine.
Pre-operative treatment with induction chemotherapy for breast cancer
Patients with WHO-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:
STEP 1 - INDUCTION/RE-INDUCTION
The patient received any induction chemotherapy regimen and may have received post-remission consolidation therapy prior to screening.
The patient has adverse risk disease or AML for which there is otherwise a substantial risk of relapse, which includes but is not limited to: adverse karyotype, FLT3 internal tandem duplication (ITD) mutation, history of antecedent hematologic disorder (AHD), therapy-related AML, history of requiring more than 1 cycle of intensive induction chemotherapy to achieve first remission, and/or presence of persistent MRD (detected by cytogenetics, molecular markers, or flow cytometry) at any point after the initial induction cycle.
Patient must be either primary refractory to one frontline induction therapy or relapsed after one frontline induction therapy; patients who do not achieve complete remission after induction therapy are also eligible
Radiation use as part of induction regimen or consolidation (within 90 days after completion of induction chemotherapy) is allowed
Refractory disease is defined by the failure to obtain a complete remission (CR) with a HDAC-containing or a standard induction regimen. Patients who require two cycles of induction therapy to attain a first CR are not considered to have refractory disease.
It must be at least 6 months since the last treatment with a \VPLD\ induction/re-induction type regimen (i.e. anthracycline, steroid, asparaginase and vincristine)
Refractory patients:\r\n* Patients must have received at least two attempts at remission induction, which may consist of up to two different therapy courses; Children's Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is one remission attempt
Within three days of starting the induction phase of therapy for ALL (B-cell, T-cell, or mixed phenotype)
Patients who are not eligible for standard anesthetic induction, e.g., those needing rapid sequence induction or awake fiberoptic bronchial intubation
Acute or chronic thrombocytopenia in patients with acute leukemia (myeloblastic or lymphoblastic) receiving induction or re-induction chemotherapy that is expected to induce marrow aplasia for at least 2 weeks; or
Patients undergoing AML induction chemotherapy with an anthracycline + cytarabine-based chemotherapy regimen
Anesthetic plan must include arterial line (femoral, radial, brachial, dorsalis pedis) either prior to induction of anesthesia or immediately after induction of anesthesia
Patient cannot previously have been on the trial for another induction, salvage, or consolidation attempt
Patients must have achieved a complete response to induction chemotherapy (+/- thoracic radiation therapy) assessed according to local habits (at least on a chest x-ray) at the time of study entry
Prior induction chemotherapy
Considered inappropriate for intensive remission induction therapy by an investigator
Receipt of induction chemotherapy
Planned use of cisplatin as induction chemotherapy.
Myelodysplastic syndromes requiring induction (myelosuppressive) chemotherapy
Subjects who are undergoing re-induction chemotherapy and have participated in this study during their first induction chemotherapy
Prior therapy with hydroxyurea, interferon, anagrelide, ruxolitinib, hypomethylating agents, Revlimid, thalidomide, steroids, other JAK inhibitors is allowed for AML patients who are back in chronic phase MPN, prior induction chemotherapy is allowed
Planned 3-4 drug systemic induction chemotherapy with a corticosteroid, vincristine and a single dose or multiple doses of asparaginase, with or without daunorubicin
MDS – may have achieved CR through either hypomethylating agent therapy, induction chemotherapy, or other therapy
Stable or better disease on re-staging scans following induction mFOLFIRINOX
Induction chemotherapy regimen
Patients must have previously untreated AML and be candidates for intensive induction chemotherapy; patients are allowed to have had prior hydroxyurea
Has AML or ALL and failed any prior induction therapy regimen or have relapsed after prior therapy
Patients that receive chemotherapy (induction or sequential)
Receiving induction treatment while hospitalized
Patient is currently undergoing AML-like intensive induction, re-induction/salvage, or consolidation chemotherapy, or planned to start such therapy within 1 week
Has completed or scheduled to begin 4-6 cycles of platinum-based induction chemotherapy that does not include a taxane\r\n* Induction may contain, but is not required to contain bevacizumab or cetuximab; induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina (UNC) principal investigator (PI) that there is no additional risk to the subject\r\n* Day 1 (D1) of treatment on LCCC1516 must be 21-42 days from the last day of induction, consistent with timing of standard of care maintenance