Intravenous (IV) Decitabine and Oral Bexarotene for Acute Myelogenous Leukemia (AML)

Washington University School of Medicine19 enrolled

Overview

The main objective is to determine the safety and tolerability of combination decitabine and bexarotene during four cycles of therapy.

The investigators are seeking to study the combination of decitabine and bexarotene. These two agents have each shown efficacy in decreasing leukemic blast counts and restoring normal hematopoiesis via different mechanisms of action and with non-overlapping side-effect profiles. By combining these agents, the investigators hope to improve overall response rates. The investigators further hope to improve platelet and neutrophil counts in an even greater number of patients, thus treating two of the most important sources of morbidity and mortality in this patient population.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Myeloid, Acute

Interventions

DecitabineDRUG

BexaroteneDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * AML with bone marrow blasts ≥ 20%. * Relapsed disease after 1 or more lines of prior salvage chemotherapy and any FAB-AML, or * Diagnosis of AML and age ≥ 60 and not a candidate for cytotoxic chemotherapy and any FAB-AML except FAB-M3. * Performance status ≤ 2. * Age ≥ 18 years. Exclusion Criteria: * Peripheral white blood cell count (WBC) \> 10,000/microliter. * Total bilirubin \> 1.5 x normal. * AST/ALT \> 2.5 x normal. * Serum creatinine \> 2 x normal. * Fasting serum triglyceride \> 1,000 mg/dL. * Active or poorly controlled graft vs host disease (GVHD). * Pregnant or nursing. * Known CNS leukemia. * History of positive HIV serology. * History of positive Hepatitis C serology. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements. * Chemotherapy within 21 days of enrollment. * Radiation therapy within 14 days of enrollment.

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Toxicity of combination decitabine and bexarotene during four cycles of therapy

Time frame: After 4 cycles of therapy

Secondary Outcomes

To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.

Time frame: After 4 cycles of therapy

To determine the rates of hematological improvement, transfusion independence, time to progression, cytogenetic response, and survival.

Time frame: Every 2 months for 2 years after first dose of study drug

To perform correlative studies defining transcriptional response to bexarotene in primary AML bone marrow cells.

Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment

To perform correlative studies examining the clonality of morphologically differentiated neutrophils by fluorescence in situ hybridization (FISH) in patients with improved neutrophil counts.

Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment

To perform correlative studies comparing the self-renewal of morphologically differentiated neutrophils and leukemic blasts by colony forming assays in patients with improved neutrophil counts.

Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment

To perform correlative studies of platelet function by PFA100 in patients with platelet counts improved to >100,000/microliter

Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment

Data from ClinicalTrials.gov

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