A Phase 2 interventional study of Azacitidine and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes, sponsored by St. Jude Children's Research Hospital. Active, not recruiting at 10 sites in United States. Open to participants aged 29 Days to 21 Years. Per ClinicalTrials.gov, last updated 2026-04-23.
Sponsored by St. Jude Children's Research Hospital · Phase 2, Interventional, and Treatment
The overall aim of this study is to determine if epigenetic priming with a DNA methyltransferase inhibitor (DMTi) prior to chemotherapy blocks is tolerable and carries evidence of a clinical efficacy signal as determined by minimal residual disease (MRD), event-free survival (EFS), and overall survival (OS). Tolerability for each of the agents, as well as total reduction in DNA methylation and outcome assessments will be done to simultaneously obtain preliminary biological and clinical data for each DMTi in parallel.
PRIMARY OBJECTIVES:
SECONDARY OBJECTIVES
To determine tolerability, priming with DMTi (azacitidine or decitabine) will be limited to Induction I and II during Part 1 of the study. If DMTi treatment is tolerated during Part 1, the investigators will go on to an Expansion Phase (Part 2) that includes DMTi priming prior to all chemotherapy blocks.
Treatment will consist of 5 blocks of conventional chemotherapy: Induction I, Induction II, Intensification I, Intensification II, and Intensification III over approximately 5 months.
RANDOMIZATION: Patients will be randomized to receive one of two DMTi (azacitidine or decitabine) for 5 days prior to Induction I. Intrathecal (ITHMA) treatments will be given right before treatment on this study or on Day 1 of Induction I treatment. Leucovorin will be given 24-30 hours following ITHMA.
INDUCTION I CHEMOTHERAPY: Patients receive cytarabine, daunorubicin, and etoposide.
INDUCTION II CHEMOTHERAPY; Patients receive their assigned DMTi for 5 days followed by fludarabine, cytarabine, G-CSF, and idarubicin.
Patients are then evaluated and assigned to either the low-risk arm, intermediate-risk arm, or the high-risk arm for Intensification therapy.
Patients with ≥ 5% blasts following Induction II will be considered refractory and will go off therapy. The rare high risk patient with an MRD \< 0.1% following Induction I may proceed directly to stem cell transplant (SCT) after Induction II - if a suitable donor is available and the transplant can be performed without delay. MDS patients may proceed to SCT once they have achieved MRD \<0.1% irrespective of the number of chemotherapy courses received.
INTENSIFICATION I CHEMOTHERAPY - LOW-RISK AML, INTERMEDIATE-RISK AML, and HIGH-RISK AML with no donor: Patients receive cytarabine and etoposide. After administration of 5 days of a DMTi prior to Inductions I and II satisfies a tolerability determination criterion, patients will also receive their randomly assigned DMTi for five days prior to cytarabine and etoposide.
INTENSIFICATION II CHEMOTHERAPY - LOW RISK AML, INTERMEDIATE-RISK AML, and HIGH-RISK AML with no donor: Patients receive mitoxantrone and cytarabine. After administration of 5 days of a DMTi prior to Inductions I and II satisfies a tolerability determination criterion, patients will also receive their randomly assigned DMTi for five days prior to mitoxantrone and cytarabine.
INTENSIFICATION I CHEMOTHERAPY - HIGH-RISK AML with a donor: Patients receive mitoxantrone and cytarabine followed by stem cell transplant (SCT). Treatment related AML patients and patients with treatment related MDS who have a donor but are not able to receive a SCT without delay will proceed to HR Intensification III and receive erwinia asparaginase and cytarabine. After administration of 5 days of a DMTi prior to earlier courses satisfies a tolerability criterion, patients will also receive their randomly assigned DMTi for five days prior to mitoxantrone and cytarabine or erwinia asparaginase and cytarabine.
Treatment related AML patients and treatment related MDS patients that are not able to receive a SCT should go off treatment following Intensification II.
INTENSIFICATION III CHEMOTHERAPY - INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor: Patients receive erwinia asparaginase and cytarabine. After administration of 5 days of a DMTi prior to earlier courses satisfies a tolerability criterion, patients will also receive their randomly assigned DMTi for five days prior to erwinia asparaginase and cytarabine.
2,970 studies on the registry are indexed under Leukemia, Myeloid, Acute; 744 are open to participants now.
This study's enrollment of 206 is above the median of 41 across 2,508 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →St. Jude Children's Research Hospital is the lead sponsor of 434 studies on the registry; 99 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 35 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Diagnostic criteria: Patients must have one of the following diagnoses:
Other criteria - Patients must meet all the following criteria:
EXCLUSION CRITERIA:
Part 1 Tolerability with AZA - Low Risk Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I \& II and then receive low-risk intensifications I \& II without azacitidine. Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: G-CSF · Drug: Dexrazoxane
Part 1 Tolerability with DAC - Low Risk Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and then receive low-risk Intensifications I \& II without decitabine. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: G-CSF · Drug: Dexrazoxane
Part 2 Dose Expansion with AZA - Low Risk Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I \& II and low- risk Intensifications I \& II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy. Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane
Part 2 Dose Expansion with DAC - Low Risk Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and low-risk Intensifications I \& II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane
Part 1 Tolerability with AZA - Intermediate Risk Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I \& II and then receive intermediate risk Intensifications I, II \& III without azacitidine. Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: G-CSF · Drug: Dexrazoxane
Part 1 Tolerability with DAC - Intermediate Risk Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and then receive intermediate-risk Intensifications I, II \& III without decitabine. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: G-CSF · Drug: Dexrazoxane
Part 2 Dose Expansion with AZA - Intermediate-Risk Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I \& II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy. Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Drug: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn
Part 2 Dose Expansion with DAC - Intermediate-Risk Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Drug: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn
Part 1 Tolerability with AZA - High Risk (no donor) Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I \& II and high-risk intensifications I, II \& III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations. Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane
Part 1 Tolerability with DAC - High Risk (no donor) Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and then receive high-risk Intensifications I, II \& III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane
Part 2 Dose Expansion with AZA - High Risk (no donor) Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I \& II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy. Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Drug: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn
Part 2 Dose Expansion with DAC - High Risk (no donor) Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Drug: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn
Part 1 Tolerability with AZA- High Risk (with donor) Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations. Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Biological: Stem Cell Transplant
Part 1 Tolerability with DAC - High Risk (with donor) Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Biological: Stem Cell Transplant
Part 2 Dose Expansion with DAC - High Risk (with donor) Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I \& II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy. Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
Drug: Decitabine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Biological: Stem Cell Transplant
Part 2 Dose Expansion with AZA - High Risk (with donor) Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I \& II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy. Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
Drug: Azacitidine · Drug: Cytarabine · Drug: Daunorubicin · Drug: Etoposide · Combination Product: ITMHA · Drug: Idarubicin · Drug: Fludarabine · Drug: Mitoxantrone · Drug: Erwinia asparaginase · Drug: Sorafenib · Drug: G-CSF · Drug: Dexrazoxane · Biological: Stem Cell Transplant
Azacitidine solution is administered intravenously (IV) over a period of 10-40 minutes.
Also known as: Vidaza®
Administered intravenously (IV) over approximately one hour.
Also known as: Dacogen®
Given IV or intrathecally (IT).
Also known as: Ara-C, Cytosar®
Given IV.
Also known as: Daunomycin, Cerubidine®
Given IV.
Also known as: Vepesid®, VP-16, Etoposide Phosphate, Etopophos®
Given IT.
Also known as: Intrathecal Triples, Methotrexate/Hydrocortisone/Cytarabine
Given IV.
Also known as: Idamycin PFS®
Given IV over approximately 30 minutes.
Also known as: Fludara®
Given IV.
Also known as: Novantrone®
Given IV or intramuscularly (IM).
Also known as: Asparaginase Erwinia chrysanthemi, Erwinaze®, Crisantaspase®
Given PO.
Also known as: Nexavar®
Given IV.
Also known as: Neupogen, Filgrastim
Given IV immediately before idarubicin administration.
Also known as: Zinecard®
The transplant protocol will depend on the patient's donor and transplant physician's preference.
Also known as: SCT
May be used in the event of an Erwinia asparaginase shortage. Given intramuscularly (IM).
Also known as: Rylaze™, Recombinant Erwinia
Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination
Patients will be monitored for grade 4-5 non-hematologic toxic events during these two courses of chemotherapy. Tolerating a course is defined as completing the course without experiencing death or a grade 4 non-hematologic toxicity.
Time frame: From enrollment to completion of chemotherapy (up to 8 months after start of therapy)
Change in genome-wide methylation burden of leukemia cells from diagnosis to after five days of single agent DMTi
Leukemic cells will be collected from patients at diagnosis and after five days of single agent DMTi. Each sample of leukemic cells will be profiled with a methylation microarray. For each leukemic sample, genome-wide methylation burden (GWMB) will be computed as the sum of methylation values across all markers. For each patient, the change in GWMB will be computed as the day 5 GWMB minus the diagnostic GWMB.
Time frame: From diagnosis to completion of five days of single agent DMTi (up to 2 weeks after start of therapy)
Cox model hazard ratio for association of event-free survival with genome-wide methylation burden
Patients will be monitored for the events of interest from enrollment for at least three years. EFS will be defined as the time elapsed from enrollment to the first of the following events: death, relapse, resistant disease, or second malignancy. EFS times for subjects who have not experienced these events at the time of analysis will be censored at date of last follow-up. A Cox regression model will be used to evaluate the association of EFS with genome-wide methylation burden observed after completion of five days of single agent decitabine or azacitidine as randomly assigned.
Time frame: From diagnosis to the first of the following events: death, relapse, resistant disease, second malignancy, or last follow-up (up to 3 years after completion of therapy)
Proportion of MRD-evaluable subjects with detectable minimal residual disease after receiving five days of a single agent DMTi followed by araC+daunorubicin+etoposide.
Flow cytometry will be used to measure minimal residual disease at diagnosis and after completion of the first course of chemotherapy.
Time frame: MRD will be measured after completion of DMTi+araC+daunorubicin+etoposide (up to 6 weeks after the start of therapy)
Kaplan-Meier estimate of event-free survival
Patients will be monitored for the events of interest from enrollment for at least three years. EFS will be defined as the time elapsed from enrollment to the first of the following events: death, relapse, resistant disease, or second malignancy. EFS times for subjects who have not experienced these events at the time of analysis will be censored at date of last follow-up.
Time frame: From diagnosis to the first of the following events: death, relapse, resistant disease, second malignancy, or last follow-up (up to 3 years after completion of therapy)
Kaplan-Meier estimate of overall survival
Patients will be monitored for death from enrollment for at least three years. Overall survival will be defined as the time elapsed from enrollment to death. OS times for subjects who are living at the time of analysis will be censored at date of last follow-up.
Time frame: From diagnosis to the first of the following events: death or last follow-up (up to 3 years after completion of therapy)
This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
St. Jude Children's Research Hospital