Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00054431

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Accelerated Phase Chronic Myelogenous Leukemia Blastic Phase Chronic Myelogenous Leukemia Childhood Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Relapsing Chronic Myelogenous Leukemia	Drug: imatinib mesylate Drug: decitabine Other: laboratory biomarker analysis	Phase 2

Detailed Description

OBJECTIVES:

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

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2003

Actual Primary Completion Date :

May 1, 2007

Arms and Interventions

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.	Drug: imatinib mesylate Given orally Other Names: CGP 57148 Gleevec Glivec Drug: decitabine Given IV Other Names: 5-aza-dCyd 5AZA DAC Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (imatinib mesylate, decitabine)

Drug: imatinib mesylate

Given orally

Other Names:

CGP 57148

Gleevec

Glivec

Drug: decitabine

Given IV

Other Names:

5-aza-dCyd

5AZA

DAC

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

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

Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [Up to 4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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