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

Leukemia, Myeloid, Acute Clinical Trial

— AML  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01001143
• Other study ID #: 09-1661 / 201012801
• Status: Completed
• Phase: Phase 1
• First received: October 19, 2009
• Last updated: July 28, 2014
• Start date: May 2010
• Est. completion date: May 2014

Study information

• Verified date: July 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: May 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Decitabine

• Bexarotene

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity of combination decitabine and bexarotene during four cycles of therapy		After 4 cycles of therapy	Yes
Secondary	To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.		After 4 cycles of therapy	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine