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DNA Methyltransferase Inhibitor

Epigenetic Priming for Acute Myeloid Leukemia

Phase 2
Waitlist Available
Led By Raul C. Ribiero, MD
Research Sponsored by St. Jude Children's Research Hospital
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Age > 28 days and < 22 years at time of study entry inclusive
Patients must have one of the following diagnoses: Acute myeloid leukemia fulfilling the criteria of the WHO Classification, 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 with confirmation of myeloid differentiation, or High grade myelodysplastic syndrome with greater than 5% blasts, or Patients with treatment related myeloid neoplasms with cumulative anthracycline dose not exceeding 230 mg/m2 doxorubicin equivalents
Must not have
Patients with treatment related myeloid neoplasms with cumulative anthracyclines greater than 230 mg/m2 doxorubicin equivalents
Acute promyelocytic leukemia (APL)
Timeline
Screening 3 weeks
Treatment Varies
Follow Up from diagnosis to completion of five days of single agent dmti (up to 2 weeks after start of therapy)
Awards & highlights
All Individual Drugs Already Approved
No Placebo-Only Group

Summary

This trial is studying how well giving azacitidine or decitabine before standard chemotherapy works in treating patients with acute myeloid leukemia.

Who is the study for?
This trial is for patients under 22 years old with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome, without prior treatment except possibly one dose of intrathecal therapy and certain emergency treatments. They must not have Down syndrome, certain other leukemias or bone marrow syndromes, uncontrolled infections, or be pregnant.
What is being tested?
The study tests if using drugs called azacitidine and decitabine (DMTis) before standard chemotherapy can help treat acute myeloid leukemia in young patients. It checks the safety of this approach and whether it affects disease markers and survival rates.
What are the potential side effects?
Possible side effects include reactions to the drugs such as nausea, fatigue, blood count changes leading to increased infection risk, liver issues, and potential allergic reactions. The exact side effects will vary depending on individual patient responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am between 1 month and 22 years old.
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I have a specific type of blood cancer or condition as per WHO guidelines.
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I am a woman who can have children and I have a negative pregnancy test from the last 2 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I have a blood disorder from treatment and received high doses of a specific chemotherapy.
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I have been diagnosed with acute promyelocytic leukemia.
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I have an ongoing infection that is not under control.
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I have been diagnosed with juvenile myelomonocytic leukemia.
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I have Fanconi anemia.
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I have been diagnosed with Kostmann syndrome.
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I have a bone marrow failure syndrome or mild MDS.
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I am not using any cancer treatments not allowed by the study.
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My condition is chronic myeloid leukemia in blast crisis.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~from diagnosis to completion of five days of single agent dmti (up to 2 weeks after start of therapy)
This trial's timeline: 3 weeks for screening, Varies for treatment, and from diagnosis to completion of five days of single agent dmti (up to 2 weeks after start of therapy) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Change in genome-wide methylation burden of leukemia cells from diagnosis to after five days of single agent DMTi
Cox model hazard ratio for association of event-free survival with genome-wide methylation burden
Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination
Secondary study objectives
Kaplan-Meier estimate of event-free survival
Kaplan-Meier estimate of overall survival
Proportion of MRD-evaluable subjects with detectable minimal residual disease after receiving five days of a single agent DMTi followed by araC+daunorubicin+etoposide.

Side effects data

From 2010 Phase 2 & 3 trial • 135 Patients • NCT00176904
40%
Death
7%
Auto recovery
1%
Primary graft failure
100%
80%
60%
40%
20%
0%
Study treatment Arm
Patients Treated With Stem Cell Transplant

Awards & Highlights

All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

16Treatment groups
Experimental Treatment
Group I: DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+SorExperimental Treatment13 Interventions
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.
Group II: DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+SorExperimental Treatment13 Interventions
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
Group III: DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+SorExperimental Treatment11 Interventions
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.
Group IV: DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+SorExperimental Treatment12 Interventions
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.
Group V: DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraCExperimental Treatment11 Interventions
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.
Group VI: DAC+ADE | DAC+FLAG+Ida | AE | MAExperimental Treatment10 Interventions
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.
Group VII: DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+SorExperimental Treatment13 Interventions
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
Group VIII: DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+SorExperimental Treatment13 Interventions
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.
Group IX: AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+SorExperimental Treatment13 Interventions
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.
Group X: AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+SorExperimental Treatment12 Interventions
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.
Group XI: AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+SorExperimental Treatment13 Interventions
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.
Group XII: AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+SorExperimental Treatment11 Interventions
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.
Group XIII: AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraCExperimental Treatment11 Interventions
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,
Group XIV: AZA+ADE | AZA+FLAG+Ida | AE | MAExperimental Treatment10 Interventions
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.
Group XV: AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+SorExperimental Treatment13 Interventions
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.
Group XVI: AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+SorExperimental Treatment13 Interventions
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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Decitabine
2004
Completed Phase 3
~1720
G-CSF
2014
Completed Phase 4
~1610
Cytarabine
2016
Completed Phase 3
~3330
Daunorubicin
2013
Completed Phase 4
~5040
Sorafenib
2014
Completed Phase 3
~2320
Etoposide
2010
Completed Phase 3
~2960
Erwinia asparaginase
2012
Completed Phase 2
~30
Idarubicin
2014
Completed Phase 4
~4380
Fludarabine
2012
Completed Phase 4
~1860
Mitoxantrone
2008
Completed Phase 3
~1550
Dexrazoxane
2016
Completed Phase 2
~80
Stem Cell Transplant
2007
Completed Phase 3
~1350
Azacitidine
2012
Completed Phase 3
~1440

Find a Location

Who is running the clinical trial?

St. Jude Children's Research HospitalLead Sponsor
443 Previous Clinical Trials
5,305,275 Total Patients Enrolled
Raul C. Ribiero, MDPrincipal InvestigatorSt. Jude Children's Research Hospital
Jeffrey E. Rubnitz, MD, PhDPrincipal InvestigatorSt. Jude Children's Research Hospital
5 Previous Clinical Trials
202 Total Patients Enrolled

Media Library

Azacitidine (DNA Methyltransferase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03164057 — Phase 2
Acute Myeloid Leukemia Research Study Groups: DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA, DAC+ADE | DAC+FLAG+Ida | AE | MA, AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor, DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor, AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC, DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC, AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor, AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor, DAC+ADE | DAC+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 | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor, DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor, AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Acute Myeloid Leukemia Clinical Trial 2023: Azacitidine Highlights & Side Effects. Trial Name: NCT03164057 — Phase 2
Azacitidine (DNA Methyltransferase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03164057 — Phase 2
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