A Phase II Open-Label Study of High-Dose Cytarabine and Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Refractory or Relapsed 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.

OUTLINE: This is an open-label phase II study. Patients are stratified according to
diagnosis (acute myeloid leukemia vs acute lymphoblastic leukemia Phase II: Patients receive
high-dose cytarabine followed by clofarabine (at the dose determined in phase I) on days
1-3.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 39 patients were 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