Imatinib Mesylate in Treating Patients With Myelofibrosis

OHSU Knight Cancer Institute

Status and phase: Terminated; Phase 2

Conditions: Chronic Myeloproliferative Disorders

Treatments: Drug: imatinib mesylate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00245128

OHSU-541 (Other Identifier)

CDR0000445435

OHSU-HEM-01071-L (Other Identifier)

Details and patient eligibility

About

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects of imatinib mesylate and how well it works in treating patients with myelofibrosis.

Full description

OBJECTIVES:

Primary

• Determine the safety, efficacy, and tolerability of imatinib mesylate in patients with myelofibrosis with myeloid metaplasia.
• Determine the 3-, 6-, and 12-month major and minor erythroid response rates in patients treated with this drug.

Secondary

• Determine reduction in marrow fibrosis in patients treated with this drug.
• Determine decrease in spleen size in patients treated with this drug.

OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.

Patients receive oral imatinib mesylate once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients who do not experience a minor erythroid response or a 50% reduction in spleen size after 6 months of treatment are removed from the study. Patients experiencing clinical benefit (e.g., ongoing erythroid response) after 1 year of treatment may continue treatment with imatinib mesylate as above at the discretion of the principal investigator.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of myelofibrosis with myeloid metaplasia (MMM), defined by all of the following:

  • Leukoerythroblastic blood picture
  • Fibrosis involving > 1/3 sectional area of bone marrow biopsy
  • Splenomegaly (unless patient has undergone prior splenectomy)
  • Philadelphia chromosome negative
  • No myelodysplastic syndrome
  • No systemic disorders associated with marrow fibrosis

• Red blood cell transfusion dependent, defined by 1 of the following:

  • Patient has required ≥ 2 units of red blood cells every 4 weeks within the past 8 weeks
  • Hemoglobin ≤ 8 g/dL on ≥ 3 occasions (≥ 2 weeks apart ) over the past 8 weeks

• No evidence of disease transformation to acute myelogenous leukemia, defined as > 20% blasts in bone marrow and/or peripheral blood

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 50,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2 times ULN (unless due to extramedullary hematopoiesis in the liver)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No New York Heart Association grade III-IV heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment
• No serious, uncontrolled medical condition
• No patients who are considered potentially unreliable or with a history of noncompliance to medical regimens

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior interferon alfa

Chemotherapy

• No concurrent chemotherapy except hydroxyurea to control elevated blood counts

Endocrine therapy

• More than 4 weeks since prior corticosteroids, danazol, or other androgens for MMM

Other

• More than 4 weeks since other prior treatment for MMM
• No other concurrent experimental drug therapy for MMM

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)