Active — Not RecruitingPhase 2

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

United States206 participantsStarted 2017-06-15

Plain-language 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.

Who can participate

Age range29 Days – 21 Years

SexALL

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INCLUSION CRITERIA: * 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. * 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 minimu…

What they're measuring

Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination

Timeframe: 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

Timeframe: 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

Timeframe: 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)

Trial details

NCT IDNCT03164057

SponsorSt. Jude Children's Research Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-09-20

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