Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia

Phase II Study of Imatinib Mesylate (Gleevec, STI-571) (NSC#716051) and Decitabine (5-AZA-2'-Deoxycitidine) (NSC#127716), in Chronic Myelogenous Leukemia in Accelerated and Blastic Phases

This phase II trial is studying how well giving imatinib mesylate together with decitabine works in treating patients with accelerated or blast phase chronic myelogenous leukemia. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving imatinib mesylate together with decitabine may kill more cancer cells

Study Overview

• Status: Completed
• Conditions: Accelerated Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Phase Chronic Myelogenous Leukemia
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: decitabine; Drug: imatinib mesylate

Detailed Description

OBJECTIVES:

I. Determine the duration of response and response rate in patients with accelerated or blastic phase chronic myelogenous leukemia treated with imatinib mesylate and decitabine.

II. Determine the survival rate of patients treated with this regimen. III. Determine the toxicity of this regimen in these patients. IV. Determine the effects of this regimen on gene methylation in the leukemic cells of these patients.

OUTLINE: Patients are stratified according to prior exposure to imatinib mesylate (yes vs no).

Patients receive oral imatinib mesylate daily and decitabine IV over 1 hour daily, 5 days per week, for 2 consecutive weeks. Courses repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 20-80 patients (10-40 per stratum) will be accrued for this study within 20 months.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed chronic myelogenous leukemia

  • Philadelphia chromosome positive by cytogenetics OR fluorescent in situ hybridization
  • Accelerated or non-lymphoid blastic phase
• Performance status - ECOG 0-2
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 2 times ULN
• Creatinine less than 2.0 mg/dL
• Normal cardiac function
• No New York Heart Association class III or IV heart disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior decitabine
• At least 2 weeks since other prior chemotherapy (unless there is evidence of rapidly progressive disease) and recovered
• Concurrent hydroxyurea allowed during the first 2 courses of study therapy in patients with rapidly progressing disease

• Prior imatinib mesylate allowed

  • Patients who received at least 4 weeks of prior imatinib mesylate must have failed therapy, as evidenced by resistance after 8 weeks or disease progression
• No concurrent grapefruit or grapefruit juice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (imatinib mesylate, decitabine); Patients receive oral imatinib mesylate daily and decitabine IV over 1 hour daily, 5 days per week, for 2 consecutive weeks. Courses repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: decitabine; Given IV; Other Names: DAC; 5-aza-dCyd; 5AZA; Drug: imatinib mesylate; Given orally; Other Names: Gleevec; CGP 57148; Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete and partial response	6 months
Hematologic improvement	Up to 1 year
Duration of response	Date of documented response until relapse, assessed up to 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0	Up to 4 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jean-Pierre Issa, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: February 5, 2003
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Cell Transformation, Neoplastic; Carcinogenesis; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Decitabine; Azacitidine; Imatinib Mesylate
• Other Study ID Numbers: NCI-2012-02516; N01CM62202 (U.S. NIH Grant/Contract); MDA-ID-02205; CDR0000270678 (Registry Identifier: PDQ (Physician Data Query))