Cytarabine and Clofarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

OBJECTIVES:

• Determine the response rate in adult patients with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia treated with high-dose cytarabine followed by clofarabine.
• Document the safety profile and tolerability of this regimen in these patients.
• Phase I: Patients receive high-dose cytarabine IV over 3 hours followed by clofarabine IV over 2 hours on days 1-5. Treatment repeats for up to 4 courses (1-2 induction courses, 2-3 post-remission courses) in the absence of disease progression or unacceptable toxicity.

A cohort of 3-6 patients receives the starting dose of clofarabine. If 1 of 6 patients experiences dose-limiting toxicity (DLT), a subsequent cohort of patients receives clofarabine at the next higher dose. If ≥ 2 of 6 patients experience DLT, the dose of cytarabine is reduced and subsequent cohorts of patients receive cytarabine at reduced doses and clofarabine as per the dose-escalation scheme above.

PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Pathologic confirmation of acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL)

• No M3 AML
• Meets 1 of the following criteria:

• In first relapse
• In second relapse after a second complete remission (CR) that lasted ≥ 3 months
• Refractory to initial induction therapy
• No symptomatic CNS involvement

PATIENT CHARACTERISTICS:

• ECOG performance status ≤ 2
• Creatinine < 2 mg/dL
• Bilirubin ≤ 2 mg/dL
• AST and ALT ≤ 4 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 weeks after completing study treatment
• Ejection fraction ≥ 45% by echocardiogram
• No active, uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant
• No psychiatric disorders that would interfere with giving consent, study participation, or follow-up procedures
• No other severe concurrent disease that would preclude study treatment

PRIOR CONCURRENT THERAPY:

• At least 1 week since prior therapy and recovered
• No other concurrent chemotherapy

• Hydroxyurea to control WBC count before starting study treatment allowed
• No concurrent corticosteroids unless used for diseases other than leukemia
• No concurrent palliative radiotherapy
• No concurrent growth factors (e.g., epoetin alfa, filgrastim [G-CSF], or sargramostim [GM-CSF]) in patients with AML