Imatinib Mesylate in Treating Patients With Myelofibrosis

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Myeloproliferative Disorders
• Intervention / Treatment: Drug: imatinib mesylate

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

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	Time Frame
Reduction in Marrow Fibrosis and Decrease in Spleen Size	After 6 and 12 months of therapy

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimate): October 27, 2005

Study Record Updates

• Last Update Posted (Estimate): January 13, 2012
• Last Update Submitted That Met QC Criteria: December 1, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: polycythemia vera; essential thrombocythemia; chronic idiopathic myelofibrosis
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Primary Myelofibrosis; Myeloproliferative Disorders; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CDR0000445435; OHSU-541 (Other Identifier: OHSU IRB); OHSU-HEM-01071-L (Other Identifier: OHSU Knight Cancer Institute)