Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

Phase II Study of Decitabine in Acute Myeloid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00492401
• Other study ID #: NCI-2009-00246
• Secondary ID: OSU 07017N01CM62
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 25, 2007
• Last updated: February 25, 2013
• Start date: May 2007

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Secondary Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Intervention

Drug:
• decitabine
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies
• high performance liquid chromatography
Correlative studies

Genetic:
• microarray analysis
Correlative studies
• 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

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete remission	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).	Every 4 weeks, assessed up to 30 days after completion of treatment	No
Secondary	Measurement of gene expression in peripheral blood or bone marrow	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.	From baseline to up to day 28 of course 1	No
Secondary	Measurement of DNA methylation in peripheral blood or bone marrow cells	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.	From baseline to up to day 28 of course 1	No
Secondary	Measurement of DNMT protein in peripheral blood or bone marrow cells	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.	From baseline to up to day 28 of course 1	No
Secondary	Measurement of HbF in peripheral blood or marrow cells	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.	From baseline to up to days 28 of course 2	No