A Phase II Study Of Gleevec (Imatinib Mesylate Formerly Known as STI-571) In Patients With Myelofibrosis
Overview
- Phase
- Phase 2
- Intervention
- imatinib mesylate
- Conditions
- Chronic Myelomonocytic Leukemia
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Clinical responses in terms of improvement in anemia and splenomegaly as previously published for myelofibrosis
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have myelofibrosis. Imatinib mesylate may stop the growth of myelofibrosis by blocking certain enzymes necessary for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the response rate (complete and partial) to STI-571 in patients with myelofibrosis. II. To determine the safety of STI-571 in patients with myelofibrosis. SECONDARY OBJECTIVES: I. To determine the effects of STI-571 on bone marrow morphology (including effects on marrow fibrosis, osteosclerosis and cellularity) in patients with myelofibrosis. II. To assess the effects of STI-571 on surrogate biologic endpoints including PDGFR expression (by immunohistochemistry), PDGFR signaling, and circulating progenitor (CD34 positive) cells. III. To determine the effects of STI-571 on bone marrow cytogenetics in patients with an abnormal karyotype. OUTLINE: This is a multicenter study. Patients are stratified according to Dupriez risk score (low vs intermediate vs high). Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologic confirmation of one of the following diseases-
- •Myeloid metaplasia with myelofibrosis (this includes all subtypes- chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia, post thrombocythemic and post polycythemic myelofibrosis) or
- •Chronic myelomonocytic leukemia (CMMOL) with t(5;12)(q31-33;p12) or TEL-PDGFRβ rearrangement; patients with CMMOL and the t(5;7)(q31-33;q11.2) or other chromosomal translocations resulting in activation of PDGFR will also be eligible
- •Patients must have anemia (hemoglobin \< 11 g/dL) or palpable splenomegaly (measured in cm from costal margin- to eligible); patients with palpable splenomegaly must have spleen size documented ultrasonographically as well; they must also meet standard diagnostic criteria for MMM\* or CMMOL; patients with MMM must have thrombocytopenia (platelet count \< 100 x 10\^9/L) to be eligible; they must be Philadelphia chromosome or (BCR/ABL) rearrangement negative
- •Patients with CMMOL must also have the t(5;12)(q31-33;p12) or TEL-PDGFRβ rearrangement to be eligible
- •The Italian diagnostic criteria for MMM
- •Necessary criteria
- •Diffuse bone marrow fibrosis
- •Absence of the Philadelphia chromosome or BCR-ABL rearrangement in peripheral blood cells
- •Optional criteria
Exclusion Criteria
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to STI-571
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because STI-571 is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with STI-571, STI-571 should not be administered patients who are breastfeeding
- •HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with STI-571; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- •Because warfarin is metabolized through the CYP450 system, and since gastrointestinal bleeding may occur with STI-571, no therapeutic anticoagulation with warfarin will be permitted in patients participating in this study; as an alternative, therapeutic anticoagulation may be accomplished using low-molecular weight heparin (e.g. Lovenox) or heparin
Arms & Interventions
Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.
Intervention: imatinib mesylate
Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Clinical responses in terms of improvement in anemia and splenomegaly as previously published for myelofibrosis
Time Frame: Up to 12 months
Frequency of adverse events graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time Frame: Up to 12 months
Exact 95% confidence intervals generated using the binomial distribution.
Secondary Outcomes
- Progression-free survival(Up to 12 months)
- Bone marrow response(Up to 12 months)