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

Not Recruiting

Trial ID: NCT03164057


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.

Official Title

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

Stanford Investigator(s)



   - 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

   - 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


   - 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

   - 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.


drug: Azacitidine

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

drug: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Zeel Patel

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