Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
|Recurrent Adult Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Azacitidine Drug: Cytarabine Drug: Etoposide Phosphate Other: Laboratory Biomarker Analysis Drug: Mitoxantrone Hydrochloride Other: Pharmacological Study||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of Azacitidine in Combination With MEC (Mitoxantrone, Etoposide, Cytarabine) in Relapsed and Refractory Acute Myeloid Leukemia|
- Maximum-tolerated dose of azacitidine when combined with salvage chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to day 42 ]Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
- Clinical response according to the International Working Group criteria [ Time Frame: Up to day 42 ]Responses will be summarized by simple descriptive summary statistics delineating complete and lesser responses as well as stable and progressive disease.
- Qualitative and quantitative toxicities of azacitidine in combination with (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) [ Time Frame: Up to 30 days post-therapy ]Graded according to NCI CTCAE version 4.0.
|Actual Study Start Date:||January 20, 2011|
|Primary Completion Date:||May 24, 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (azacitidine, mitoxantrone, etoposide, cytarabine)
Patients receive azacitidine IV over 30 minutes on days 1-8 and mitoxantrone hydrochloride IV over 10 minutes, etoposide phosphate IV over 30-60 minutes, and cytarabine IV over 6 hours on days 3-8. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
Given IVDrug: Cytarabine
Given IVDrug: Etoposide Phosphate
Given IVOther: Laboratory Biomarker Analysis
Correlative studiesDrug: Mitoxantrone Hydrochloride
Given IVOther: Pharmacological Study
I. To determine the maximum-tolerated dose of azacitidine (5-azaC) when combined with mitoxantrone hydrochloride (mitoxantrone), etoposide phosphate (etoposide), and cytarabine (MEC) as salvage chemotherapy in patients with relapsed or refractory acute myeloid leukemia (AML).
I. To define the qualitative and quantitative toxicities of 5-azaC with MEC in combination with regard to organ specificity, time course, predictability, and reversibility.
II. To document the rate of complete remission (CR) and CR with incomplete blood count recovery (CRi) for this combination of agents as well as overall survival, relapse-free survival, and event-free survival.
III. To evaluate the pharmacokinetics of 5-azaC when given in combination with MEC in patients enrolled on this study.
IV. To measure R2 downregulation, including changes in R2 target, AraCTP, and dNTP/NTP pools, of 5-azaC in combination with MEC and correlate these pharmacodynamic endpoints with clinical response.
VI. To evaluate hypomethylation, including DMNT1 expression, Sp1 expression, global deoxyribonucleic acid (DNA) methylation, gene expression profiling, and micro ribonucleic acid (RNA) expression profiling, of 5-azaC when given in combination with MEC and correlate these pharmacodynamic changes with clinical response.
OUTLINE: This is a dose-escalation study of azacitidine.
Patients receive azacitidine intravenously (IV) over 30 minutes on days 1-8 and mitoxantrone hydrochloride IV over 10 minutes, etoposide phosphate IV over 30-60 minutes, and cytarabine IV over 6 hours on days 3-8. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01249430
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Alison Walker||Ohio State University Comprehensive Cancer Center|