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Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia

Phase 2
Terminated
Conditions
Leukemia
Registration Number
NCT00015847
Lead Sponsor
OHSU Knight Cancer Institute
Brief Summary

RATIONALE: Imatinib mesylate and interferon alfa may interfere with the growth of the cancer cells. Combining imatinib mesylate with interferon alfa may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining imatinib mesylate with interferon alfa in treating patients who have chronic myelogenous leukemia.

Detailed Description

OBJECTIVES:

* Determine the maximum tolerated dose of interferon alfa administered with imatinib mesylate in patients with chronic phase chronic myelogenous leukemia. (Phase I closed to accrual as of 7/9/03.)

* Determine the safety and tolerability of this regimen in this patient population.

* Determine the complete, major, and minor cytogenetic response rates and complete hematologic response rate in patients after 6 and 12 months of treatment with this regimen.

* Determine the molecular response (reverse transcriptase-polymerase chain reaction for bcr-abl) rate in patients who have a complete cytogenetic response after 6 and 12 months of treatment with this regimen.

* Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

* Phase I (closed to accrual as of 7/9/03): Patients receive oral imatinib mesylate once daily beginning on day 1 and interferon alfa (IFN-A) subcutaneously once daily or 3 times weekly beginning on day 14. Courses repeat every 35 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of 1 year of therapy, patients may receive additional therapy, provided that the patient is benefiting from imatinib mesylate. IFN-A is discontinued in patients who achieve a molecular remission that is confirmed on 2 successive bone marrow samples. Imatinib mesylate is discontinued in patients who achieve and maintain a molecular remission for 2 years.

Sequential dose escalation of IFN-A is followed by sequential dose escalation of imatinib mesylate. Cohorts of 3-6 patients receive escalating doses of IFN-A and then imatinib mesylate until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

* Phase II: Patients receive imatinib mesylate and IFN-A as in phase I at the established MTD.

Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for the phase I portion of this study. (Phase I closed to accrual as of 7/9/03.) A total of 40 patients will be accrued for the phase II portion of the study within 3-4 months.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
25
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Complete Cytogenetic Response at 6 and 12 Months (Phase II)At 6 and 12 months during phase II

Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows:

Complete\* (0% Ph-positive cells) Partial\* (1-34%) Minor (35-95%) None (96-100%).

Minor Cytogenetic Response at 6 and 12 Months (Phase II)At 6 and 12 months during phase II
Complete Hematologic Response at 6 and 12 Months (Phase II)At 6 and 12 months during phase II
Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II)At 6 and 12 months during phase II
Treatment-related Toxicity (i.e., Grade 3 or 4 Nonhematologic Toxicity) as Measured by NCI CTCAE v3.0 (Phase I)12 Months

1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death

Major Cytogenetic Response After 6 and 12 Months of Treatment.6 and 12 months after treatment

Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows:

Complete\* (0% Ph-positive cells) Partial\* (1-34%) Minor (35-95%) None (96-100%).

\*Major cytogenetic response includes complete and partial cytogenetic response.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (2)

OHSU Knight Cancer Institute

🇺🇸

Portland, Oregon, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

🇺🇸

Chicago, Illinois, United States

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