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
- 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
- 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
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
- Phase II: Patients receive imatinib mesylate and IFN-A as in phase I at the established
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete Cytogenetic Response at 6 and 12 Months (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%).
At 6 and 12 months during phase II
Brian J. Druker, MD
OHSU Knight Cancer Institute
United States: Federal Government
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|OHSU Knight Cancer Institute||Portland, Oregon 97239|