Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia; Accelerated Phase Chronic Myelogenous Leukemia

Treatments: Other: laboratory biomarker analysis; Drug: decitabine; Drug: imatinib mesylate

Study type: Interventional

Funder types: NIH

Identifiers

NCT00054431

NCI-2012-02516

N01CM62202 (U.S. NIH Grant/Contract)

MDA-ID-02205

CDR0000270678 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 80 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

Treatment (imatinib mesylate, decitabine)

Experimental group

Description:

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.

Treatment:

Drug: imatinib mesylate

Other: laboratory biomarker analysis

Drug: decitabine