Overview

This trial is active, not recruiting.

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
Treatments decitabine, laboratory biomarker analysis, pharmacological study, high performance liquid chromatography, microarray analysis, rna analysis, mass spectrometry, dna methylation analysis, matrix-assisted laser desorption/ionization time of flight mass spectrometry
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date May 2007
End date December 2010
Trial size 40 participants
Trial identifier NCT00492401, N01CM62207, NCI-2009-00246, OSU 07017

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
decitabine 5-aza-dCyd
Given IV
laboratory biomarker analysis
Correlative studies
pharmacological study pharmacological studies
Correlative studies
high performance liquid chromatography HPLC
Correlative studies
microarray analysis gene expression profiling
Correlative studies
rna analysis
Correlative studies
mass spectrometry
Correlative studies
dna methylation analysis
Correlative studies
matrix-assisted laser desorption/ionization time of flight mass spectrometry MALDI-TOF Mass Spectrometry
Correlative studies

Primary Outcomes

Measure
Rate of complete remission
time frame: Every 4 weeks, assessed up to 30 days after completion of treatment

Secondary Outcomes

Measure
Measurement of gene expression in peripheral blood or bone marrow
time frame: From baseline to up to day 28 of course 1
Measurement of DNA methylation in peripheral blood or bone marrow cells
time frame: From baseline to up to day 28 of course 1
Measurement of DNMT protein in peripheral blood or bone marrow cells
time frame: From baseline to up to day 28 of course 1
Measurement of HbF in peripheral blood or marrow cells
time frame: From baseline to up to days 28 of course 2

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase II Study of Decitabine in Acute Myeloid Leukemia
Principal investigator William Blum
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).