Clinical Trial: Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

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

Official Title: Phase I Investigation of the Feasibility of Combining 5-azacytidine With Highdose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy in a Sequential Manner for Remission Induction in High-risk Acute Mye

Brief Summary: This phase I trial studies the side effects and best dose of azacitidine when given together with cytarabine and mitoxantrone hydrochloride in treating patients with high-risk acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, cytarabine, and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also help cytarabine and mitoxantrone hydrochloride work better by making the cancer cells more sensitive to the drugs

Detailed Summary:

PRIMARY OBJECTIVES:

I. To establish the recommended phase II dose of 5-azacytidine (azacitidine) when combined with high-dose cytarabine (HiDAC) and mitoxantrone (mitoxantrone hydrochloride) chemotherapy in high-risk acute myeloid leukemia (AML) patients.

SECONDARY OBJECTIVES:

I. To determine the complete remission (CR) rate following the use of induction chemotherapy regimen of 5-azacytidine followed by high-dose cytarabine (HiDAC) and mitoxantrone chemotherapy in high-risk AML patients.

II. To determine the toxicity of the combination regimen. III. To determine the disease-free survival (DFS) and overall survival (OS) of the patient population.

IV. To determine the gene expression levels of topoisomerase II and deoxycytidine kinase in leukemia blasts pre-treatment and following therapy with 5-azacytidine.

V. To collect specimens for banking for use in future research studies with a view to elucidating the predictors of response to epigenetic therapies.

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

INDUCTION: Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) once daily (QD) on days 1-5, cytarabine IV over 4 hours on days 6 and 10, and mitoxantrone hydrochloride IV over 60 minutes on days 6 and 10.

CONSOLIDATION: Patients receive azacitidine IV over 10-40 minutes or SC QD on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients ineligible for allogen
Sponsor: University of Chicago

Current Primary Outcome: Recommended phase II dose of azacitidine when combined with high-dose cytarabine and mitoxantrone hydrochloride, based on incidence of dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Toxicity Criteria, version 4 [ Time Frame: 56 days ]

DLT defined as any grade 4 or greater non-hematologic toxicity (except transient [less than 48 hours] nausea/vomiting, transient [less than 48 hours] liver function test derangements) or a grade 3 non-hematological toxicity lasting more than 7 days. Persistent bone marrow aplasia (in the absence of bone marrow involvement with disease) lasting more than 56 days would also be regarded as a DLT.


Original Primary Outcome: Same as current

Current Secondary Outcome: Change in gene expression levels of topoisomerase II and deoxycytidine kinase in leukemic blasts pre-treatment and following therapy with azacitidine will be measured by real-time polymerase chain reaction (RT-PCR) [ Time Frame: From baseline to day 56 ]

Will be compared using a two-sample t test. If the data do not appear to be normally distributed, a Wilcoxon rank sum test will be used in place of the t-test. Normality will be assessed using graphical techniques, such as normality probability plots.


Original Secondary Outcome: Same as current

Information By: University of Chicago

Dates:
Date Received: April 19, 2013
Date Started: June 2012
Date Completion: December 2017
Last Updated: October 24, 2016
Last Verified: October 2016