The goals of this study are to learn about the effectiveness, the side-effects, if waiting to give the idarubicin and cytarabine may change the side effects or effectiveness, and to identify factors to predict for responses to this therapy. The trial will examine combination of three chemotherapy drugs. These drugs are decitabine, idarubicin, and cytarabine.
PRIMARY OBJECTIVES: I. To determine the morphologic complete remission (CR) rates using a decitabine (DAC)-priming followed by idarubicin (IDA) and cytarabine (ARAC) in patients with relapsed or refractory acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To determine CR without minimal residual disease (CRMRD-), CR with incomplete blood count recovery (CRi), CR with minimal residual disease (CRMRD+), and CR with incomplete blood count recovery and with minimal residual disease (CRiMRD+) rates. II. To estimate the frequency and severity of regimen-related toxicities. III. To identify biomarkers (e.g., deoxyribonucleic acid \[DNA\] methylation and expression changes including interferon regulatory factor \[IRF\]8) associated with clinical responses. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive decitabine intravenously (IV) over 1 hour on days -4 to 0, cytarabine IV continuously over 24 hours on days 1-7, and idarubicin IV over 10-15 minutes on days 1-3. ARM II: Patients receive decitabine IV over 1 hour on days -9 to -5 and cytarabine and idarubicin as in Arm I. In both arms, treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Number of Participants Who Achieved Morphologic CR
Morphologic complete remission (CR): Absolute Neutrophil Count (ANC)≥1,000/uL, platelet count ≥100,000/uL, \<5% Bone Marrow (BM) blasts, no Auer rods (cytoplasmic inclusions which result from an abnormal fusion of the primary (azurophilic) granules), no morphologic dysplasia, and no evidence of extramedullary disease
Time frame: Participants were monitored up until the point when they went off study following completion of the treatment (3 months)
Resistant Disease Defined as Patient Survives at Least 14 Days After Completion of the Last Dose of Induction or Re-induction But Has Persistent Leukemia in Peripheral Blood (PB) or BM
Time frame: Assessed for up to 90 days
Cytogenetic Response Defined as no Detectable Cytogenetic Abnormality in a Subsequent BM Specimen After Induction or Re-induction
Time frame: Assessed for up to 5 years
CRMRD- Defined as Morphologic CR Without Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers
Time frame: Assessed for up to 5 years
CRi Defined as Meeting All Criteria for a Morphologic CR But ANC Remains Less Than 1,000/μL and/or Platelet Count Less Than 100,000/μL
Time frame: Assessed for up to 5 years
CRMRD+ Defined as a Morphologic CR But With Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers
Time frame: Assessed for up to 5 years
CRiMRD+ Defined as Meeting All Criteria for a CRi But With Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers
Time frame: Assessed for up to 5 years
TRM With Each Course of Decitabine-priming, Idarubicin, and Cytarabine
Time frame: Assessed for up to Day 30
Frequency and Severity of Grade 3, 4, and 5 Toxicities With Each Course of Decitabine-priming, Idarubicin, and Cytarabine According to NCI Common Terminology Criteria for Adverse Events Version (CTCAE) 4.0
Time frame: Assessed for up to 3 months after completion study treatment
Severe Prolonged Aplasia
Time frame: Assessed for up to 45 days
Duration of Severe Neutropenia Defined as an ANC Less Than 500
Time frame: Assessed for up to 5 years
Duration of Moderate Neutropenia Defined as an ANC Less Than 1000
Time frame: Assessed for up to 5 years
Duration of Thrombocytopenia Defined as Platelet Count Less Than 100,000
Time frame: Assessed for up to 5 years
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