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