Imatinib Mesylate in Treating Patients With Myelofibrosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Pilot Study to Determine the Safety and Preliminary Efficacy of Imatinib Mesylate (Gleevec) in Patients With Myelofibrosis With Myeloid Metaplasia

Conditions
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Chronic Myeloproliferative Disorders

Intervention / Treatment
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* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: imatinib mesylate|Once daily oral administration of Imatinib Mesylate at a dose of 600mg for 12 months.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Major and/or Minor Erythroid Responses at 3, 6, and 12 Months of Therapy | A major response = transfusion independent or a>2.0g/dl rise in hemoglobin without transfusion maintained for at least 8 weeks. Minor response= > 1 to 2.0g/dl incremental rise in hemoglobin maintained for at lease 8 weeks with a decrease in transfusion requirements of at least 50% compared to the mean transfusion requirement during the 8 week pre-study period. | At 3,6, and 12 months of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Marrow Fibrosis and Decrease in Spleen Size |  | After 6 and 12 months of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic idiopathic myelofibrosis, polycythemia vera, essential thrombocythemia