imatinib mesylate and interferon alfa in treating patients with chronic myelogenous leukemia

Conditions: Leukemia

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.

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.

Eligibility criteria:
disease characteristics: * cytogenetically confirmed chronic myelogenous leukemia (cml) * less than 15% blasts in peripheral blood or bone marrow * less than 30% blasts and promyelocytes in peripheral blood or bone marrow * less than 20% basophils in blood or bone marrow * platelet count at least 100,000/mm\^3 * no leukemia beyond bone marrow, blood, liver, or spleen * no chloroma * phase i (closed to accrual as of 7/9/03): * philadelphia (ph) chromosome-positive cml in chronic phase * phase ii: * newly diagnosed ph chromosome-positive cml in chronic phase * initial diagnosis within 6 months of study * no prior therapy for cml except hydroxyurea and/or anagrelide hydrochloride * phase i (closed to accrual as of 7/9/03) and ii: * no identified sibling donors where allogeneic stem cell transplantation is elected as first-line therapy patient characteristics: age: * 18 and over performance status: * ecog 0-2 life expectancy: * not specified hematopoietic: * see disease characteristics hepatic: * bilirubin no greater than 1.5 times upper limit of normal (uln) * ast or alt no greater than 2 times uln renal: * creatinine no greater than 1.5 times uln cardiovascular: * no new york heart association class iii or iv heart disease other: * not pregnant or nursing * negative pregnancy test * fertile patients must use 2 methods of effective barrier contraception during and for at least 3 months after study participation * no other serious uncontrolled medical condition * no autoimmune disease * no prior noncompliance to medical regimens or potential unreliability * no prior grade 3 or greater non-hematologic toxicity due to prior interferon (phase i \[closed to accrual as of 7/9/03\]) prior concurrent therapy: biologic therapy: * see disease characteristics * no prior bone marrow or peripheral blood stem cell transplantation * at least 2 weeks since prior interferon alfa (phase i \[closed to accrual as of 7/9/03\]) chemotherapy: * see disease characteristics * at least 6 weeks since prior busulfan (phase i \[closed to accrual as of 7/9/03\] ) * at least 2 weeks since prior cytarabine (phase i \[closed to accrual as of 7/9/03\]) * no concurrent chemotherapy * concurrent hydroxyurea allowed during the first 3 months of study endocrine therapy: * not specified radiotherapy: * not specified surgery: * not specified other: * at least 4 weeks since prior investigational agents other than imatinib mesylate (phase i \[closed to accrual as of 7/9/03\]) * no concurrent grapefruit juice * concurrent anagrelide hydrochloride allowed during the first 3 months of study

Keywords: relapsing chronic myelogenous leukemia chronic phase chronic myelogenous leukemia philadelphia chromosome positive chronic myelogenous leukemia