Temsirolimus and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

Inclusion Criteria:

• Histologically confirmed chronic myelogenous leukemia (CML)

  • Philadelphia chromosome-positive OR Bcr-Abl-positive disease, meeting 1 of the following criteria:

    • Accelerated phase, defined by at least 1 of the following:

      • 10-19% blasts in the peripheral blood or bone marrow
      • At least 20% basophils in peripheral blood or bone marrow
      • Platelet count < 100,000/mm^3 (unrelated to therapy)
      • Platelet count > 1,000,000/mm^3 (unresponsive to therapy)
      • Increasing splenomegaly AND increasing WBC count (unresponsive to therapy)
      • Clonal evolution

    • Blast phase, defined by 1 of the following:

      • At least 20% blasts in peripheral blood or bone marrow
      • Extramedullary disease

    • Chronic phase, defined by all of the following:

      • Less than 10% blasts in peripheral blood or bone marrow
      • Less than 20% basophils in peripheral blood or bone marrow
      • Platelet count > 100,000/mm^3
      • Absence of clonal evolution

• May have received and/or failed prior imatinib mesylate therapy

  • Patients not previously treated with imatinib mesylate receive oral imatinib mesylate once daily 14 days before beginning study drug

    • Must be able to tolerate 600 mg per day of imatinib mesylate before starting CCI-779

  • Patients with chronic phase disease must have failed prior imatinib mesylate at a dose ≥ 600 mg/day, as defined by 1 of the following:

    • Must not have achieved or must have lost hematologic response within 3 months after the start of imatinib mesylate
    • Must not have achieved or must have lost cytogenetic response after 6 months of treatment with imatinib mesylate
    • Must not have achieved or must have lost major cytogenetic response after 12 months of treatment with imatinib mesylate
    • Must have lost complete cytogenetic response
• Bone marrow aspirate and biopsy with cytogenetics and fluorescent in situ hybridization confirming t(9;22) completed within the past 28 days
• Performance status - SWOG 0-2
• More than 3 months
• See Disease Characteristics
• Bilirubin normal
• AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if suspected liver involvement with leukemia)
• Creatinine normal
• Creatinine clearance > 60 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Ejection fraction ≥ 50% by echocardiogram or MUGA scan for patients with known positive cardiac history (e.g., heart failure, coronary artery disease, cardiomegaly on prior chest x-ray, or valvular heart disease)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Fasting cholesterol ≤ 350 mg/dL
• Fasting triglycerides ≤ 400 mg/dL
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to temsirolimus or imatinib mesylate
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No other active malignancy except nonmelanoma skin cancer
• No other uncontrolled illness
• At least 48 hours since prior interferon alfa for CML
• At least 6 weeks since prior stem cell transplantation
• No concurrent biologic agents
• No concurrent prophylactic colony-stimulating factors
• At least 24 hours since prior hydroxyurea for CML
• At least 7 days since prior mercaptopurine or vinca alkaloids for CML
• At least 7 days since prior low-dose cytarabine (< 30 mg/m^2 every 12-24 hours) for CML
• At least 14 days since prior homoharringtonine for CML
• At least 14 days since prior moderate-dose cytarabine (100-200 mg/m^2 for 5-7 days) for CML
• At least 21 days since prior anthracyclines, mitoxantrone, cyclophosphamide, etoposide, or methotrexate for CML
• At least 28 days since prior high-dose cytarabine (1-3 g/m^2 every 12-24 hours for 6-12 doses) for CML
• At least 6 weeks since prior busulfan for CML
• No concurrent hydroxyurea
• No other concurrent chemotherapy
• At least 7 days since prior steroids for CML
• No prior organ transplantation
• More than 2 weeks since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)
• Recovered from all prior therapy
• Prior experimental therapy allowed provided completion of treatment corresponds to a duration > 5 half-lives of the experimental drug or any known active metabolite before study
• No concurrent cyclosporine
• No concurrent anagrelide
• No concurrent oral anticoagulants, including warfarin
• No concurrent CYP3A4 inducers or inhibitors
• No concurrent tacrolimus
• No concurrent plasmapheresis
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapies