Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Brief Title

Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Official Title

Phase II Study of Decitabine in Acute Myeloid Leukemia

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Rate of Complete Remission

Secondary Outcome

 Measurement of DNA Methylation in Peripheral Blood or Bone Marrow Cells

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

decitabine

Study Arms / Comparison Groups

 Treatment (chemotherapy)

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

55

Start Date

May 2007

Completion Date

October 2014

Primary Completion Date

December 2010

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

William Blum, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00492401

Organization ID

NCI-2009-00246

Secondary IDs

OSU 07017

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

William Blum, Principal Investigator, Ohio State University

Verification Date

May 2016