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

The Washington University

Status and phase: Completed; Phase 1

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: Bexarotene; Drug: Decitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT01001143

09-1661 / 201012801

Details and patient eligibility

About

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

Full description

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 3 patient groups

Dose Level 1

Experimental group

Description:

Decitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days. Bexarotene 100 mg/m2 PO daily for each 28 day cycle.

Treatment:

Drug: Decitabine

Drug: Bexarotene

Dose Level 2

Experimental group

Description:

Decitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days. Bexarotene 200 mg/m2 PO daily for each 28 day cycle.

Treatment:

Drug: Decitabine

Drug: Bexarotene

Dose Level 3

Experimental group

Description:

Decitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days. Bexarotene 300 mg/m2 PO daily for each 28 day cycle.

Treatment:

Drug: Decitabine

Drug: Bexarotene