Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

Treatments: Genetic: microarray analysis; Drug: decitabine; Other: pharmacological study; Genetic: DNA methylation analysis; Genetic: RNA analysis; Other: high performance liquid chromatography; Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry; Other: mass spectrometry; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: NIH

Identifiers

NCT00492401

N01CM62207 (U.S. NIH Grant/Contract)

OSU 07017

NCI-2009-00246

Details and patient eligibility

About

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

Full 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.

Enrollment: 55 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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55 participants in 1 patient group

Treatment (chemotherapy)

Experimental group

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.

Treatment:

Genetic: DNA methylation analysis

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

Other: high performance liquid chromatography

Other: laboratory biomarker analysis

Other: pharmacological study

Drug: decitabine

Genetic: RNA analysis

Other: mass spectrometry

Genetic: microarray analysis