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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01001143
First received: October 19, 2009
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Leukemia, Myeloid, Acute
Drug: Decitabine
Drug: Bexarotene
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of Intravenous Decitabine in Combination With Oral Bexarotene in Patients With Acute Myeloid Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Toxicity of combination decitabine and bexarotene during four cycles of therapy [ Time Frame: After 4 cycles of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy. [ Time Frame: After 4 cycles of therapy ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: May 2010
Study Completion Date: May 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Decitabine
Other Name: Dacogen®
Drug: Bexarotene
Other Name: Targretin®
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.

Drug: Decitabine
Other Name: Dacogen®
Drug: Bexarotene
Other Name: Targretin®
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.

Drug: Decitabine
Other Name: Dacogen®
Drug: Bexarotene
Other Name: Targretin®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01001143

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Amanda Cashen, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01001143     History of Changes
Other Study ID Numbers: 09-1661 / 201012801
Study First Received: October 19, 2009
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Bexarotene
Decitabine
Anticarcinogenic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014