Clinical trial NCT00492401: Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia
Official title: Phase II Study of Decitabine in Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-06-27
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of Complete Remission
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Measurement of DNA Methylation in Peripheral Blood or Bone Marrow Cells
timeFrame: From baseline to up to day 28 of course 1
measure: Measurement of DNMT Protein in Peripheral Blood or Bone Marrow Cells
timeFrame: Pre treatment
measure: Measurement of HbF in Peripheral Blood or Marrow Cells
timeFrame: From baseline to up to days 28 of course 2
measure: Measurement of Gene Expression in Peripheral Blood or Bone Marrow
timeFrame: From baseline to up to day 28 of course 1
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: William Blum
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1073/pnas.1002650107. Epub 2010 Apr 5.