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

NCT01001143 | Completed Phase 1

• 1 other identifier: 09-1661 / 201012801
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Toxicity of combination decitabine and bexarotene during four cycles of therapy

  After 4 cycles of therapy

Secondary Outcomes (6)

• 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

Study Arms (3)

Dose Level 1

EXPERIMENTAL

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; Drug: Bexarotene

Dose Level 2

EXPERIMENTAL

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; Drug: Bexarotene

Dose Level 3

EXPERIMENTAL

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; Drug: Bexarotene

Interventions

Decitabine DRUG

Also known as: Dacogen®

Dose Level 1; Dose Level 2; Dose Level 3

Bexarotene DRUG

Also known as: Targretin®

Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; Bexarotene

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Amanda Cashen, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2009
• First Posted: October 23, 2009
• Study Start: May 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: July 29, 2014

Record last verified: 2014-07

Locations

US (1)