Clinical Trial: Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of Azacitidine in Combination With MEC (Mitoxantrone, Etoposide, Cytarabine) in Relapsed and Refractory Acute Myeloid Leukemia.

Brief Summary: This phase I clinical trial is studying the side effects and best dose of azacitidine when given together with mitoxantrone, etoposide phosphate, and cytarabine in treating patients with relapsed or refractory acute myeloid leukemia. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide phosphate, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may help mitoxantrone, etoposide phosphate, and cytarabine work better by making cancer cells more sensitive to the drugs.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose of azacitidine when combined with salvage chemotherapy comprising mitoxantrone hydrochloride, etoposide phosphate, and cytarabine (MEC) in patients with relapsed or refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To define the qualitative and quantitative toxicities of azacitidine in combination with MEC 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) in patients treated with this combination of agents.

III. To determine the overall survival, relapse-free survival, and event-free survival of patients treated with this combination of agents.

IV. To evaluate the pharmacokinetics of azacitidine when given in combination with MEC in patients enrolled on this study. (Exploratory) V. To measure R2 down regulation, including changes in R2 target, AraCTP, and dNTP/NTP pools, of azacitidine when given in combination with MEC and to correlate these pharmacodynamic endpoints with clinical response. (Exploratory) VI. To evaluate hypomethylation, including DMNT1 expression, Sp1 expression, global DNA methylation, gene expression profiling, and microRNA expression profiling, of azacitidine when given in combination with MEC and to correlate these pharmacodynamic changes with clinical response. (Exploratory)

OUTLINE: This is a dose-escalation study of azacitidine.

Patients receive azacitidine IV over 30 minutes on days 1-8 and mit
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Maximum-tolerated dose of azacitidine when combined with salvage chemotherapy (mitoxantrone hydrochloride, etoposide, and cytarabine [MEC]) via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: By day 42 ]

Frequency distributions and other descriptive measures will form the basis of the analysis of these variables


Original Primary Outcome:

  • Maximum-tolerated dose of azacitidine when combined with salvage chemotherapy comprising mitoxantrone hydrochloride, etoposide phosphate, and cytarabine (MEC)
  • Tolerability of azacitidine in combination with MEC


Current Secondary Outcome:

  • Clinical response according to the International Working Group criteria [ Time Frame: 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 MEC graded via NCI CTCAE v4.0 [ Time Frame: Up to 30 days post-therapy ]


Original Secondary Outcome: Clinical response to azacitidine in combination with MEC

Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 25, 2010
Date Started: January 2011
Date Completion:
Last Updated: May 23, 2017
Last Verified: December 2016