sti571 in treating patients with recurrent leukemia

Conditions: Leukemia

Summary: rationale: imatinib mesylate may interfere with the growth of cancer cells and may be an effective treatment for leukemia. purpose: phase i trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent leukemia.

objectives: * determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with recurrent philadelphia chromosome-positive leukemia. * characterize the pharmacokinetic behavior of this drug in this patient population. * determine preliminarily the antileukemic activity of this drug in these patients. outline: this is a dose-escalation, multicenter study. patients receive oral imatinib mesylate (sti571) once daily for 28 days. treatment continues in the absence of unacceptable toxicity or disease progression. cohorts of 3-6 patients receive escalating doses of sti571 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed every 6 months for 4 years and then annually thereafter. projected accrual: a maximum of 32 patients will be accrued for this study within 3.5 years.

Eligibility criteria:
disease characteristics: * recurrent philadelphia (ph) chromosome-positive leukemia * recurrent or refractory acute lymphoblastic or myeloblastic leukemia or * chronic myelogenous leukemia with resistance to interferon alfa with any of the following: * wbc at least 20,000/mm\^3 after at least 3 months of interferon therapy * at least 100% increase in wbc to at least 20,000/mm\^3 confirmed over 2 weeks while receiving interferon alfa * at least 66% ph chromosome-positive cells after 1 year of interferon therapy * at least 30% increase in number of ph chromosome-positive cells after an interferon-induced response while continuing interferon therapy patient characteristics: age: * under 22 performance status: * karnofsky 50-100% if over 10 years of age or * lansky 50-100% if 10 years of age and under life expectancy: * at least 8 weeks hematopoietic: * see disease characteristics hepatic: * bilirubin no greater than 1.5 times normal * sgpt less than 3 times normal * albumin greater than 2 g/dl renal: * creatinine no greater than 1.5 times normal or * creatinine clearance or radioisotope glomerular filtration rate at least 70 ml/min other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * if prior allogeneic stem cell transplantation, no uncontrolled graft-versus -host disease * no seizure disorder if on anticonvulsants * no uncontrolled infection * no cns toxicity greater than grade 2 prior concurrent therapy: biologic therapy: * see disease characteristics * at least 1 week since prior biologic therapy and recovered * at least 3 months since prior stem cell transplantation (sct) * at least 1 week since prior growth factors * at least 1 week since prior interferon alfa chemotherapy: * recovered from prior chemotherapy * at least 6 weeks since prior busulfan and nitrosoureas * at least 2 weeks since prior homoharringtonine * at least 1 week since low-dose cytarabine * at least 2 weeks since prior moderate-dose cytarabine * at least 4 weeks since prior high-dose cytarabine * at least 3 weeks since all other prior cytotoxic chemotherapies * no prior hydroxyurea endocrine therapy: * must be on a stable dose of steroids if received prior allogeneic sct radiotherapy: * recovered from prior radiotherapy * at least 2 weeks since prior local palliative radiotherapy (small port) * at least 6 months since prior craniospinal radiotherapy * at least 6 months since prior radiotherapy to 50% or more of the pelvis * at least 6 weeks since other prior substantial bone marrow radiotherapy surgery: * not specified other: * no other concurrent investigational agents * no concurrent anticonvulsants

Keywords: recurrent childhood acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia relapsing chronic myelogenous leukemia chronic myelogenous leukemia, bcr-abl1 positive childhood chronic myelogenous leukemia