Acute Myeloid LeukemiaPhase 2NCT03164057
A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase 2 study testing Azacitidine, Decitabine and Cytarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by St. Jude Children's Research Hospital at 10 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 29 days to 21 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Azacitidine, Decitabine and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 206 participants
- Where
- 10 sitesUnited States
- Study dates
- 15 Jun 2017to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 29 days to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnostic criteria: Patients must have one of the following diagnoses:
- Acute myeloid leukemia fulfilling the criteria of the WHO Classification (see Appendix I), or
- >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
- 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
- High grade myelodysplastic syndrome (MDS) with greater than 5% blasts, or
- Patients with treatment related myeloid neoplasms including AML and MDS, provided their cumulative anthracycline dose has not exceeded 230 mg/m2 doxorubicin equivalents.
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- Other criteria - Patients must meet all the following criteria:
- Age > 28 days and < 22 years at time of study entry inclusive, and
- No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m2 per day for one week or less for hyperleukocytosis), and
- Written informed consent according to institutional guidelines, and
- Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment, and
- Male and female participants of reproductive potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
Who cannot join
- Down syndrome
- Acute promyelocytic leukemia (APL)
- BCR-ABL1 chronic myeloid leukemia in blast crisis (CML-BC)
- Juvenile myelomonocytic leukemia (JMML)
- Fanconi anemia (FA)
- Kostmann syndrome
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- Shwachman syndrome
- Other bone marrow failure syndromes or low grade (<5% bone marrow blasts) MDS.
- Use of concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy for this malignancy within 2 weeks before study entry with the exception of IT therapy, hydroxyurea, or low-dose cytarabine as specified in the protocol document. The patient must have recovered from all acute toxicities from any previous therapy.
- Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- Pregnant or lactating.
- Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
- Prior chemotherapy, with the exception of hydroxyurea or low-dose cytarabine as specified in the protocol document. The patient must have recovered from all acute toxicities from any previous therapy.
- Patients with treatment related myeloid neoplasms with cumulative anthracyclines greater than 230 mg/m2 doxorubicin equivalents.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago Children's Hospital (Comer)
Chicago, Illinois, 60637
Children's Hospital of Michigan
Detroit, Michigan, 48201
Cook Children's Medical Center
Fort Worth, Texas, 76104
Children's Hospital of Central California
Madera, California, 93636
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Children's Hospital of Orange County
Orange, California, 92968
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304
Rady Children's Hospital and Health Center
San Diego, California, 92123
Sanford Children's Specialty Clinic
Sioux Falls, South Dakota, 57117
About this study
Official title: A Phase II Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
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:
Read more
- Evaluate the tolerability of five days of epigenetic priming with azacitidine and decitabine as a single agent DMTi prior to standard AML chemotherapy blocks.
- Evaluate the change in genome-wide methylation burden induced by five days of epigenetic priming and the association of post-priming genome-wide methylation burden with event-free survival among pediatric AML patients.
SECONDARY OBJECTIVES
- Describe minimal residual disease levels following Induction I chemotherapy in patients that receive DMTi.
- Estimate the event-free survival and overall survival of patients receiving a DMTi prior to chemotherapy courses.
Read the detailed description
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.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- Azacitidine, Decitabine, Cytarabine, Daunorubicin, Etoposide
- Keywords
- DNA methyltransferase inhibitors, Acute myeloid leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza®
Azacitidine solution is administered intravenously (IV) over a period of 10-40 minutes.
DecitabineDrug
Also called Dacogen®
Administered intravenously (IV) over approximately one hour.
CytarabineDrug
Also called Ara-C, Cytosar®
Given IV or intrathecally (IT).
DaunorubicinDrug
Also called Daunomycin, Cerubidine®
Given IV.
EtoposideDrug
Also called Vepesid®, VP-16, Etoposide Phosphate, Etopophos®
Given IV.
ITMHACombination product
Also called Intrathecal Triples, Methotrexate/Hydrocortisone/Cytarabine
Given IT.
IdarubicinDrug
Also called Idamycin PFS®
Given IV.
FludarabineDrug
Also called Fludara®
Given IV over approximately 30 minutes.
MitoxantroneDrug
Also called Novantrone®
Given IV.
Erwinia asparaginaseDrug
Also called Asparaginase Erwinia chrysanthemi, Erwinaze®, Crisantaspase®
Given IV or intramuscularly (IM).
SorafenibDrug
Also called Nexavar®
Given PO.
G-CSFDrug
Also called Neupogen, Filgrastim
Given IV.
DexrazoxaneDrug
Also called Zinecard®
Given IV immediately before idarubicin administration.
Stem Cell TransplantBiological
Also called SCT
The transplant protocol will depend on the patient's donor and transplant physician's preference.
Asparaginase Erwinia Chrysanthemi, Recombinant-RywnDrug
Also called Rylaze™, Recombinant Erwinia
May be used in the event of an Erwinia asparaginase shortage. Given intramuscularly (IM).
| Study group | Role | What they receive |
|---|---|---|
| AZA+ADE | AZA+FLAG+Ida | AE | MA | Experimental | 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. Receives: Drug: Azacitidine; Drug: Cytarabine; Drug: Daunorubicin; Drug: Etoposide; Combination Product: ITMHA; Drug: Idarubicin; Drug: Fludarabine; Drug: Mitoxantrone; Drug: G-CSF; Drug: Dexrazoxane |
| DAC+ADE | DAC+FLAG+Ida | AE | MA | Experimental | 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. Receives: Drug: Decitabine; Drug: Cytarabine; Drug: Daunorubicin; Drug: Etoposide; Combination Product: ITMHA; Drug: Idarubicin; Drug: Fludarabine; Drug: Mitoxantrone; Drug: G-CSF; Drug: Dexrazoxane |
| AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor | Experimental | 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. Receives: Drug: Azacitidine; Drug: Cytarabine; Drug: Daunorubicin; Drug: Etoposide; Combination Product: ITMHA; Drug: Idarubicin; Drug: Fludarabine; Drug: Mitoxantrone; Drug: Sorafenib; Drug: G-CSF; Drug: Dexrazoxane |
| DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor | Experimental | 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. Receives: Drug: Decitabine; Drug: Cytarabine; Drug: Daunorubicin; Drug: Etoposide; Combination Product: ITMHA; Drug: Idarubicin; Drug: Fludarabine; Drug: Mitoxantrone; Drug: Sorafenib; Drug: G-CSF; Drug: Dexrazoxane |
| AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC | Experimental | 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, Receives: 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 |
| DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC | Experimental | 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. Receives: 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 |
| AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor | Experimental | 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. Receives: 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 |
| DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor | Experimental | 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 Receives: 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 |
| DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor | Experimental | 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 Receives: 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 |
| AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor | Experimental | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: From diagnosis to the first of the following events: death or last follow-up (up to 3 years after completion of therapy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2017
- Study start15 Jun 2017
- Primary completion20 Sep 2025
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raul C. Ribiero, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03164057
- Sponsor's protocol ID
- AML16
- Other IDs
- NCI-2017-00928
- Status last verified
- Apr 2026
- First submitted
- 19 May 2017
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03164057
- Acronym / sponsor ID
- AML16
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Keywords
- DNA methyltransferase inhibitors, Acute myeloid leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 206 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 15 Jun 2017 (actual)
- Primary completion
- 20 Sep 2025 (actual)
- Study completion
- Jun 2027 (estimated)
- First posted
- 23 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Evaluate the tolerability of five days of epigenetic priming with azacitidine and decitabine as a single agent DMTi prior to standard AML chemotherapy blocks.
- Evaluate the change in genome-wide methylation burden induced by five days of epigenetic priming and the association of post-priming genome-wide methylation burden with event-free survival among pediatric AML patients.
SECONDARY OBJECTIVES
- Describe minimal residual disease levels following Induction I chemotherapy in patients that receive DMTi.
- Estimate the event-free survival and overall survival of patients receiving a DMTi prior to chemotherapy courses.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 16
| Arm | Type | Receives |
|---|---|---|
| AZA+ADE | AZA+FLAG+Ida | AE | MA | Experimental | Drug: Azacitidine, Drug: Cytarabine, Drug: Daunorubicin, Drug: Etoposide, Combination Product: ITMHA, Drug: Idarubicin, Drug: Fludarabine, Drug: Mitoxantrone, Drug: G-CSF, Drug: DexrazoxanePart 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. |
| DAC+ADE | DAC+FLAG+Ida | AE | MA | Experimental | Drug: Decitabine, Drug: Cytarabine, Drug: Daunorubicin, Drug: Etoposide, Combination Product: ITMHA, Drug: Idarubicin, Drug: Fludarabine, Drug: Mitoxantrone, Drug: G-CSF, Drug: DexrazoxanePart 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. |
| AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor | Experimental | Drug: Azacitidine, Drug: Cytarabine, Drug: Daunorubicin, Drug: Etoposide, Combination Product: ITMHA, Drug: Idarubicin, Drug: Fludarabine, Drug: Mitoxantrone, Drug: Sorafenib, Drug: G-CSF, Drug: DexrazoxanePart 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. |
| DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor | Experimental | Drug: Decitabine, Drug: Cytarabine, Drug: Daunorubicin, Drug: Etoposide, Combination Product: ITMHA, Drug: Idarubicin, Drug: Fludarabine, Drug: Mitoxantrone, Drug: Sorafenib, Drug: G-CSF, Drug: DexrazoxanePart 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. |
| AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC | Experimental | Drug: Azacitidine, Drug: Cytarabine, Drug: Daunorubicin, Drug: Etoposide, Combination Product: ITMHA, Drug: Idarubicin, Drug: Fludarabine, Drug: Mitoxantrone, Drug: Erwinia asparaginase, Drug: G-CSF, Drug: DexrazoxanePart 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, |
| DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC | Experimental | Drug: Decitabine, Drug: Cytarabine, Drug: Daunorubicin, Drug: Etoposide, Combination Product: ITMHA, Drug: Idarubicin, Drug: Fludarabine, Drug: Mitoxantrone, Drug: Erwinia asparaginase, Drug: G-CSF, Drug: DexrazoxanePart 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. |
| AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor | Experimental | 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-RywnPart 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. |
| DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor | Experimental | 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-RywnPart 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. |
| AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor | Experimental | 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: DexrazoxanePart 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. |
| DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor | Experimental | 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: DexrazoxanePart 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. |
| AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor | Experimental | 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-RywnPart 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. |
| DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor | Experimental | 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-RywnPart 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. |
| AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor | Experimental | 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 TransplantPart 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. |
| DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor | Experimental | 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 TransplantPart 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 |
| DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor | Experimental | 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 TransplantPart 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 |
| AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor | Experimental | 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 TransplantPart 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. |
Who may qualify
- Ages
- 29 days to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Diagnostic criteria: Patients must have one of the following diagnoses:
- Other criteria - Patients must meet all the following criteria:
Key exclusion criteria (15 listed)
- Down syndrome
- Acute promyelocytic leukemia (APL)
- BCR-ABL1 chronic myeloid leukemia in blast crisis (CML-BC)
- Juvenile myelomonocytic leukemia (JMML)
- Fanconi anemia (FA)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: Vidaza®Azacitidine solution is administered intravenously (IV) over a period of 10-40 minutes. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor |
| DecitabineAlso: Dacogen®Administered intravenously (IV) over approximately one hour. | Drug | DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| CytarabineAlso: Ara-C, Cytosar®Given IV or intrathecally (IT). | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| DaunorubicinAlso: Daunomycin, Cerubidine®Given IV. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| EtoposideAlso: Vepesid®, VP-16, Etoposide Phosphate, Etopophos®Given IV. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| ITMHAAlso: Intrathecal Triples, Methotrexate/Hydrocortisone/CytarabineGiven IT. | Combination product | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| IdarubicinAlso: Idamycin PFS®Given IV. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| FludarabineAlso: Fludara®Given IV over approximately 30 minutes. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| MitoxantroneAlso: Novantrone®Given IV. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| Erwinia asparaginaseAlso: Asparaginase Erwinia chrysanthemi, Erwinaze®, Crisantaspase®Given IV or intramuscularly (IM). | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| SorafenibAlso: Nexavar®Given PO. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| G-CSFAlso: Neupogen, FilgrastimGiven IV. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| DexrazoxaneAlso: Zinecard®Given IV immediately before idarubicin administration. | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
| Stem Cell TransplantAlso: SCTThe transplant protocol will depend on the patient's donor and transplant physician's preference. | Biological | AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor |
| Asparaginase Erwinia Chrysanthemi, Recombinant-RywnAlso: Rylaze™, Recombinant ErwiniaMay be used in the event of an Erwinia asparaginase shortage. Given intramuscularly (IM). | Drug | AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor, DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor |
Primary outcome
Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination
Time frame: From enrollment to completion of chemotherapy (up to 8 months after start of therapy)
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.
Change in genome-wide methylation burden of leukemia cells from diagnosis to after five days of single agent DMTi
Time frame: From diagnosis to completion of five days of single agent DMTi (up to 2 weeks after start of therapy)
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.
Cox model hazard ratio for association of event-free survival with genome-wide methylation burden
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)
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.
3 secondary outcomes
Proportion of MRD-evaluable subjects with detectable minimal residual disease after receiving five days of a single agent DMTi followed by araC+daunorubicin+etoposide.
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
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
Time frame: From diagnosis to the first of the following events: death or last follow-up (up to 3 years after completion of therapy)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raul C. Ribiero, MD principal investigator
St. Jude Children's Research Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine, Decitabine and Cytarabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by St. Jude Children's Research Hospital at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination (time frame: From enrollment to completion of chemotherapy (up to 8 months after start of therapy)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.