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A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
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.
A Phase II Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
- 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.
combination product: ITMHA
drug: Erwinia asparaginase
biological: Stem Cell Transplant
drug: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn
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