Imatinib Mesylate in Treating Patients With Myelofibrosis

Chronic Myeloproliferative Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00245128
• Other study ID #: CDR0000445435
• Secondary ID: OHSU-541OHSU-HEM
• Status: Terminated
• Phase: Phase 2
• First received: October 25, 2005
• Last updated: December 1, 2011
• Start date: August 2005
• Est. completion date: October 2011

Study information

• Verified date: December 2011
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: October 2011
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Myeloproliferative Disorders
• Primary Myelofibrosis

Intervention

Drug:
• imatinib mesylate
Once daily oral administration of Imatinib Mesylate at a dose of 600mg for 12 months.

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Reduction in Marrow Fibrosis and Decrease in Spleen Size		After 6 and 12 months of therapy	No