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Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00492401
First received: June 25, 2007
Last updated: September 12, 2012
Last verified: August 2012
History of Changes

June 25, 2007
September 12, 2012
May 2007
January 2100   (final data collection date for primary outcome measure)
Rate of complete remission [ Time Frame: Every 4 weeks, assessed up to 30 days after completion of treatment ] [ Designated as safety issue: No ]
Assessment of clinical response will be made according to International Working Group criteria. The major criteria for judging response will include physical examination and examination of blood and bone marrow. For the primary endpoint, all enrolled patients will be analyzed together (regardless of age).
Rate of complete remission
Complete list of historical versions of study NCT00492401 on ClinicalTrials.gov Archive Site
  • Measurement of gene expression in peripheral blood or bone marrow [ Time Frame: From baseline to up to day 28 of course 1 ] [ Designated as safety issue: No ]
    Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.
  • Measurement of DNA methylation in peripheral blood or bone marrow cells [ Time Frame: From baseline to up to day 28 of course 1 ] [ Designated as safety issue: No ]
    Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.
  • Measurement of DNMT protein in peripheral blood or bone marrow cells [ Time Frame: From baseline to up to day 28 of course 1 ] [ Designated as safety issue: No ]
    Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.
  • Measurement of HbF in peripheral blood or marrow cells [ Time Frame: From baseline to up to days 28 of course 2 ] [ Designated as safety issue: No ]
    Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.
Measurement of gene expression and methylation, DNMT protein, and fetal hemoglobin (HbF) in peripheral blood or bone marrow
 
 
 
Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia
Phase II Study of Decitabine in Acute Myeloid Leukemia

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

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.
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Drug: decitabine
    Given IV
    Other Names:
    • 5-aza-dCyd
    • 5AZA
    • DAC
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Other: high performance liquid chromatography
    Correlative studies
    Other Name: HPLC
  • Genetic: microarray analysis
    Correlative studies
    Other Name: gene expression profiling
  • Genetic: RNA analysis
    Correlative studies
  • Other: mass spectrometry
    Correlative studies
  • Genetic: DNA methylation analysis
    Correlative studies
  • Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry
    Correlative studies
    Other Name: MALDI-TOF Mass Spectrometry
Experimental: 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.
Interventions:
  • Drug: decitabine
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
  • Other: high performance liquid chromatography
  • Genetic: microarray analysis
  • Genetic: RNA analysis
  • Other: mass spectrometry
  • Genetic: DNA methylation analysis
  • Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry
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. Epub 2010 Apr 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
 
January 2100   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00492401
NCI-2009-00246, OSU-07017, CDR0000552701, N01CM62207
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
 
Principal Investigator: William Blum Ohio State University
National Cancer Institute (NCI)
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP