Intravenous (IV) Decitabine and Oral Bexarotene for Acute Myelogenous Leukemia (AML) (AML)
July 28, 2014 updated by: Washington University School of Medicine
A Phase I Dose Escalation Study of Intravenous Decitabine in Combination With Oral Bexarotene in Patients With Acute Myeloid Leukemia (AML)
The main objective is to determine the safety and tolerability of combination decitabine and bexarotene during four cycles of therapy.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Missouri
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St. Louis, Missouri, United States, 63110
- Washington University School of Medicine
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Dose Level 1
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. |
Other Names:
Other Names:
|
|
Experimental: Dose Level 2
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. |
Other Names:
Other Names:
|
|
Experimental: Dose Level 3
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. |
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Toxicity of combination decitabine and bexarotene during four cycles of therapy
Time Frame: After 4 cycles of therapy
|
After 4 cycles of therapy
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.
Time Frame: After 4 cycles of therapy
|
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
|
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
|
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
|
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
|
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
|
Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2010
Primary Completion (Actual)
May 1, 2013
Study Completion (Actual)
May 1, 2014
Study Registration Dates
First Submitted
October 19, 2009
First Submitted That Met QC Criteria
October 22, 2009
First Posted (Estimate)
October 23, 2009
Study Record Updates
Last Update Posted (Estimate)
July 29, 2014
Last Update Submitted That Met QC Criteria
July 28, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 09-1661 / 201012801
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.