Clinical trial NCT00015847
Conditions: Leukemia
Keywords: relapsing chronic myelogenous leukemia chronic phase chronic myelogenous leukemia Philadelphia chromosome positive chronic myelogenous leukemia
Sponsor: OHSU Knight Cancer Institute
Start date: 2001-04-01; Completion date: 2011-05-01
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Interventions: intervention 1: recombinant interferon alfa intervention 2: imatinib mesylate
Intervention descriptions: intervention 1: IFN-α will be given at a dose ranging up to 5 MIU daily via subcutaneous injection. intervention 2: Once daily oral administration of STI571 (imatinib mesylate) at a dose of 400 mg or 600mg for 12 months.

Protocol documents: