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

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

Detailed Description
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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.

Official Title
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A Phase I Dose Escalation Study of Intravenous Decitabine in Combination With Oral Bexarotene in Patients With Acute Myeloid Leukemia (AML)

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Decitabine
* Drug: Bexarotene


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>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. | Drug: Decitabine<br> <br> * Other names: Dacogen®;Drug: Bexarotene<br> <br> * Other names: Targretin®;|
| Experimental: Dose Level 2<br>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. | Drug: Decitabine<br> <br> * Other names: Dacogen®;Drug: Bexarotene<br> <br> * Other names: Targretin®;|
| Experimental: Dose Level 3<br>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. | Drug: Decitabine<br> <br> * Other names: Dacogen®;Drug: Bexarotene<br> <br> * Other names: Targretin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of combination decitabine and bexarotene during four cycles of therapy |  | After 4 cycles of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy. |  | After 4 cycles of therapy | 
| To determine the rates of hematological improvement, transfusion independence, time to progression, cytogenetic response, and survival. |  | 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. |  | 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. |  | 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. |  | 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 |  | Baseline, C1D3, Day 25 of even cycles, and End of Study treatment |