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

Primary Purpose

Leukemia, Myeloid, Acute

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Decitabine
Bexarotene
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Level 1

Dose Level 2

Dose Level 3

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

Toxicity of combination decitabine and bexarotene during four cycles of therapy

Secondary Outcome Measures

To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.
To determine the rates of hematological improvement, transfusion independence, time to progression, cytogenetic response, and survival.
To perform correlative studies defining transcriptional response to bexarotene in primary AML bone marrow cells.
To perform correlative studies examining the clonality of morphologically differentiated neutrophils by fluorescence in situ hybridization (FISH) in patients with improved neutrophil counts.
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.
To perform correlative studies of platelet function by PFA100 in patients with platelet counts improved to >100,000/microliter

Full Information

First Posted
October 19, 2009
Last Updated
July 28, 2014
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01001143
Brief Title
Intravenous (IV) Decitabine and Oral Bexarotene for Acute Myelogenous Leukemia (AML)
Acronym
AML
Official Title
A Phase I Dose Escalation Study of Intravenous Decitabine in Combination With Oral Bexarotene in Patients With Acute Myeloid Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1
Arm Type
Experimental
Arm 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.
Arm Title
Dose Level 2
Arm Type
Experimental
Arm 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.
Arm Title
Dose Level 3
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
Dacogen®
Intervention Type
Drug
Intervention Name(s)
Bexarotene
Other Intervention Name(s)
Targretin®
Primary Outcome Measure Information:
Title
Toxicity of combination decitabine and bexarotene during four cycles of therapy
Time Frame
After 4 cycles of therapy
Secondary Outcome Measure Information:
Title
To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.
Time Frame
After 4 cycles of therapy
Title
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
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Cashen, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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