Clofarabine and Temsirolimus in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia

An Open Label Phase II Trial of Clofarabine and Temsirolimus in Older Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving clofarabine together with temsirolimus may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving clofarabine together with temsirolimus works in treating older patients with relapsed or refractory acute myeloid leukemia.

OBJECTIVES:

Primary

• To determine the complete response rate in older patients with relapsed or refractory acute myeloid leukemia when treated with low-dose clofarabine and temsirolimus.

Secondary

• To determine the tolerability and safety of this regimen.
• To determine the duration of response.
• To determine the duration of survival.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive clofarabine IV over 1 hour on days 1-5 and temsirolimus IV over 30 minutes on days 1, 8, and 15. Treatment continues for 1-2 courses in the absence of disease progression or unacceptable toxicity.
• Maintenance therapy: Patients achieving morphologic complete remission (CR) or CR with incomplete blood count recovery receive temsirolimus IV over 30 minutes on days 1 and 8 of each month. Treatment continues for 12 months in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Cytologically confirmed acute myeloid leukemia (AML) meeting the following criteria:

  • At least 20% of blasts in the bone marrow
  • AML in first relapse OR refractory to no more than one prior combination of intensive chemotherapy induction regimen

• No acute promyelocytic leukemia

• No blast transformation of chronic myeloid leukemia or other myeloproliferative disorders

• No active CNS leukemia

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy ≥ 4 weeks
• Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN)*
• AST and ALT ≤ 2.5 times ULN*
• Serum creatinine ≤ 1.0 mg/dL* OR estimated glomerular filtration rate > 60 mL/min
• No active uncontrolled systemic infection
• No concurrent active malignancy
• No HIV positivity
• No severe concurrent medical condition or psychiatric disorder that would preclude study participation NOTE: *Unless due to organ leukemic involvement

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 2 weeks since prior myelosuppressive chemotherapy
• At least 48 hours since prior hydroxyurea
• No prior clofarabine or temsirolimus
• No prior allogeneic stem cell transplantation
• No investigational drug within the past 30 days