imatinib mesylate and 17-n-allylamino-17-demethoxygeldanamycin in treating patients with chronic myelogenous leukemia

Conditions: Leukemia

Summary: rationale: imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. drugs used in chemotherapy such as 17-n-allylamino-17-demethoxygeldanamycin use different ways to stop cancer cells from dividing so they stop growing or die. combining imatinib mesylate with chemotherapy may kill more cancer cells. purpose: this phase i trial is studying the side effects and best dose of 17-n-allylamino-17-demethoxygeldanamycin when given together with imatinib mesylate in treating patients with chronic myelogenous leukemia.

objectives: * determine the maximum tolerated dose and dose-limiting toxicity of 17-n-allylamino-17-demethoxygeldanamycin (17-aag) when administered with imatinib mesylate in patients with chronic myelogenous leukemia. * determine the pharmacokinetics of this regimen in these patients. outline: this is an open-label, nonrandomized, multicenter, dose-escalation study of 17-n-allylamino-17-demethoxygeldanamycin (17-aag). patients receive oral imatinib mesylate on days 1-21 and 17-aag iv over 1 hour on days 1, 4, 8, and 12. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of 17-aag until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, an additional cohort of 6-10 patients receives treatment at the recommended phase ii dose. projected accrual: approximately 21-42 patients will be accrued for this study within 1.5 years.

Eligibility criteria:
disease characteristics: * diagnosis of chronic myelogenous leukemia, including any of the following phases: * blastic phase * greater than 30% blasts in the peripheral blood or bone marrow * previously untreated disease or refractory to or relapsed after most recent therapy * accelerated phase, defined by 1 of the following: * at least 15, but less than 30%, blasts in the peripheral blood or bone marrow * at least 30% blasts and promyelocytes in the peripheral blood or bone marrow * greater than 20% peripheral blood basophilia * chronic phase * no major cytogenetic response (less than 65% philadelphia chromosome negative) after 12 months of prior imatinib mesylate therapy * philadelphia chromosome positive by routine cytogenetics patient characteristics: age * 18 and over performance status * ecog 0-2 life expectancy * at least 3 months hematopoietic * not specified hepatic * bilirubin no greater than 1.5 mg/dl * alt and ast no greater than 2.5 times upper limit of normal renal * creatinine less than 1.5 mg/dl cardiovascular * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no known allergy to eggs * able to swallow pills * no ongoing or active infection * no psychiatric illness or social situation that would preclude study compliance * no other concurrent uncontrolled medical illness prior concurrent therapy: biologic therapy * no prior stem cell transplantation chemotherapy * more than 4 weeks since prior chemotherapy (except hydroxyurea or anagrelide) (at least 6 weeks for nitrosoureas or mitomycin) endocrine therapy * not specified radiotherapy * more than 4 weeks since prior radiotherapy surgery * no prior liver, kidney, or lung transplantation * more than 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery) other * prior imatinib mesylate administered within the past 4 weeks is allowed * no concurrent tacrolimus or cyclosporine as immunosuppressive agents * no other concurrent investigational agents * no concurrent combination antiretroviral therapy for hiv-positive patients * no concurrent agents that alter cyp3a4 activity, including any of the following: * grapefruit juice * ketoconazole * fluconazole * itraconazole * erythromycin * clarithromycin * cimetidine * terfenadine * astemizole * hiv protease inhibitors (e.g., indinavir and nelfinavir)

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