A Phase I/II Dose-Finding Study to Determine the Safety, Tolerability, and Anti-Leukemic Effects of STI571 (NSC 716051) in Combination With Interferon-alpha in Patients With Chronic Myelogenous Leukemia in Chronic Phase
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- OHSU Knight Cancer Institute
- Enrollment
- 25
- Locations
- 4
- Primary Endpoint
- Complete Cytogenetic Response at 6 and 12 Months (Phase II)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 120 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Complete Cytogenetic Response at 6 and 12 Months (Phase II)
Time Frame: 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)
Time Frame: At 6 and 12 months during phase II
Complete Hematologic Response at 6 and 12 Months (Phase II)
Time Frame: At 6 and 12 months during phase II
Molecular Response in Patients With Complete Cytogenetic Response at 6 and 12 Months (Phase II)
Time Frame: 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)
Time Frame: 12 Months
1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death
Major Cytogenetic Response After 6 and 12 Months of Treatment.
Time Frame: 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 Outcomes
No secondary outcomes reported