A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia

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). 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.

Conditions

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes

Interventions

DRUG

Azacitidine

Azacitidine solution is administered intravenously (IV) over a period of 10-40 minutes.

DRUG

Decitabine

Administered intravenously (IV) over approximately one hour.

DRUG

Cytarabine

Given IV or intrathecally (IT).

DRUG

Daunorubicin

Given IV.

DRUG

Etoposide

Given IV.

COMBINATION_PRODUCT

ITMHA

Given IT.

DRUG

Idarubicin

Given IV.

DRUG

Fludarabine

Given IV over approximately 30 minutes.

DRUG

Mitoxantrone

Given IV.

DRUG

Erwinia asparaginase

Given IV or intramuscularly (IM).

DRUG

Sorafenib

Given PO.

DRUG

G-CSF

Given IV.

DRUG

Dexrazoxane

Given IV immediately before idarubicin administration.

BIOLOGICAL

Stem Cell Transplant

The transplant protocol will depend on the patient's donor and transplant physician's preference.

DRUG

Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn

May be used in the event of an Erwinia asparaginase shortage. Given intramuscularly (IM).

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Raul C. Ribiero, MD · St. Jude Children's Research Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

29 Days

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-06-15

Primary Completion

2025-09-20

Completion

2027-06-30

FDA Drug

Yes

Countries

• United States

Study Locations