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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: February 25, 2013
Last verified: February 2013
History of Changes
  Purpose

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


Condition Intervention Phase
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
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
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Decitabine in Acute Myeloid Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 40
Study Start Date: May 2007
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00492401

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: William Blum Ohio State University
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00492401     History of Changes
Other Study ID Numbers: NCI-2009-00246, OSU 07017, N01CM62207
Study First Received: June 25, 2007
Last Updated: February 25, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Decitabine
 Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013