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