Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

NCT ID: NCT00492401

Last Updated: 2016-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2014-10-31

Brief Summary

This phase II trial is studying how well decitabine works in treating patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the rate of complete remission (CR) in patients with previously untreated acute myeloid leukemia treated with decitabine.

SECONDARY OBJECTIVES:

I. Determine the rate of overall survival at 1 year in patients treated with this drug.

II. Determine the overall response rate (CR, incomplete CR, and partial remission) in patients treated with this drug.

III. Correlate the biological activity of decitabine with clinical endpoints and maximum concentration of plasma decitabine.

IV. Correlate intracellular concentration of decitabine with global DNA methylation, other biological endpoints, and clinical response.

OUTLINE:

Patients receive decitabine IV over 1 hour on days 1-10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow aspiration and blood sample collection periodically for pharmacological and correlative studies. Samples are analyzed for gene expression, methylation of gene promoters, fetal hemoglobin (HgF), DNMT1 protein expression, maximum concentration of plasma decitabine, and global DNA methylation. Samples are analyzed by RT-PCR, Bio-COBRA, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, SDS-PAGE (polyacrylamide gel electrophoresis), immunoblotting, and LC-MS/MS.

After completion of study treatment, patients are followed for at least 30 days.

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (chemotherapy)

Patients receive decitabine IV over 1 hour on days 1-10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

decitabine

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

high performance liquid chromatography

Intervention Type: OTHER

Correlative studies

microarray analysis

Intervention Type: GENETIC

Correlative studies

RNA analysis

Intervention Type: GENETIC

Correlative studies

mass spectrometry

Intervention Type: OTHER

Correlative studies

DNA methylation analysis

Intervention Type: GENETIC

Correlative studies

matrix-assisted laser desorption/ionization time of flight mass spectrometry

Intervention Type: OTHER

Correlative studies

Interventions

decitabine

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

high performance liquid chromatography

Correlative studies

Intervention Type: OTHER

microarray analysis

Correlative studies

Intervention Type: GENETIC

RNA analysis

Correlative studies

Intervention Type: GENETIC

mass spectrometry

Correlative studies

Intervention Type: OTHER

DNA methylation analysis

Correlative studies

Intervention Type: GENETIC

matrix-assisted laser desorption/ionization time of flight mass spectrometry

Correlative studies

Intervention Type: OTHER

Other Intervention Names

5-aza-dCyd; 5AZA; DAC; pharmacological studies; HPLC; gene expression profiling; MALDI-TOF Mass Spectrometry

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed acute myeloid leukemia (AML) meeting 1 of the following criteria:

• At least 60 years of age and not a candidate for or refused standard induction treatment
• Poor risk cytogenetics
• AML following antecedent hematologic disorder
• Therapy-related AML
• Secondary AML
• No granulocytic sarcoma as sole site of disease
• No active CNS disease or CNS relapse
• ECOG performance status 0-2
• Life expectancy > 6 months
• Total bilirubin < 2.0 mg/dL
• Creatinine < 2.0 mg/dL
• AST and ALT < 2.5 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No NYHA class III or IV congestive heart failure
• No uncontrolled infection
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine that are not easily managed
• No other uncontrolled illness including, but not limited to, any of the following:

• Symptomatic congestive heart failure
• Unstable angina pectoris
• Serious cardiac arrhythmia
• Psychiatric illness or social situations that would preclude compliance with study requirements
• No active second malignancy involving the blood or marrow or likely to progress and require therapy in the next 6 months
• No prior therapy for AML except emergency leukapheresis or hydroxyurea for leukocytosis
• No prior azacitidine or decitabine
• No prior cytarabine or other conventional chemotherapy agents for antecedent hematologic disorders

• Prior myeloid growth factors, recombinant erythropoietin, thalidomide, or lenalidomide allowed
• No concurrent palliative radiotherapy
• No other concurrent investigational agents
• No other concurrent direct anti-leukemia therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Blum

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

References

Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, Liu S, Havelange V, Becker H, Schaaf L, Mickle J, Devine H, Kefauver C, Devine SM, Chan KK, Heerema NA, Bloomfield CD, Grever MR, Byrd JC, Villalona-Calero M, Croce CM, Marcucci G. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7473-8. doi: 10.1073/pnas.1002650107. Epub 2010 Apr 5.

Reference Type: DERIVED

PMID: 20368434 (View on PubMed)

Other Identifiers

OSU 07017

Identifier Type: -

Identifier Source: secondary_id

N01CM62207

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00246

Identifier Type: -

Identifier Source: org_study_id