S0530 Cytarabine and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

Primary objective:

• Determine whether the complete remission rate in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) is sufficiently high after treatment with cytarabine and clofarabine to warrant further investigation.

Secondary objectives:

• Estimate the frequency and severity of toxicities associated with this dosing schedule of cytarabine and clofarabine.
• Investigate, preliminarily, the prognostic effects of cytogenetic features on response to treatment in these patients.

Other objectives (if funding allows):

• Investigate, preliminarily, the prognostic effects of laboratory correlates (expression of nucleoside transporters, expression of other pertinent genes by tissue microarray) and FISH features on response to treatment in these patients

OUTLINE: This is an open-label, multicenter study.

• Induction therapy (1 or 2 courses): Patients receive induction therapy comprising clofarabine IV over 1 hour followed 4 hours later by cytarabine IV over 2 hours on days 1-5 (course 1). Patients who achieve a response (5-25% blasts in the bone marrow with a ≥ 50% reduction in blasts from initial bone marrow aspirate) receive 1 more course of induction therapy beginning no later than day 45. Patients who achieve complete remission (< 5% blasts in the bone marrow) after 1 or 2 courses of induction therapy may proceed to consolidation therapy.
• Consolidation therapy (1 course): Beginning within 60 days after the first day of the last induction therapy, patients may receive consolidation therapy comprising clofarabine IV over 1 hour followed 4 hours later by cytarabine IV over 2 hours on days 1-4.

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

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Prior morphologic diagnosis of acute lymphoblastic leukemia (ALL)

• No M0, mixed lineage, or L3 (Burkitt's) ALL
• Refractory to a standard induction regimen OR relapsed after successful prior induction therapy

• Standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or high-dose cytarabine/mitoxantrone
• Any number of inductions or remissions allowed
• Must have evidence of ALL in bone marrow or peripheral blood

• Immunophenotyping of the blood or bone marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell)
• No extramedullary only disease in the absence of bone marrow or blood involvement
• Co-expression of myeloid antigens (CD13 and CD33) allowed
• Patients with Philadelphia chromosome-positive (Ph+) ALL or bcr/abl-positive ALL who were previously eligible for imatinib mesylate treatment must have received imatinib mesylate either alone or in combination with chemotherapy for ALL and must have either failed treatment or been unable to tolerate treatment
• No CNS involvement as determined by lumbar puncture (for previous CNS history or clinical signs or symptoms of CNS) or by clinical exam (if no previous history or signs/symptoms)
• Must be registered on SWOG-S9910 and SWOG-9007

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 1.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• No psychiatric disorders that would interfere with study compliance
• No uncontrolled systemic fungal, bacterial, viral, or other infection
• No other severe concurrent disease
• No other serious or poorly controlled medical condition that would preclude study participation
• No history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would preclude study participation
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No pre-existing motor or sensory neuropathy ≥ grade 2
• No other prior malignancies, except for the following:

• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• Adequately treated stage I or II cancer in complete remission
• Any other prior cancer for which the patient has been disease free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• No prior clofarabine
• More than 2 weeks since prior chemotherapy, major surgery, or other investigational agents
• More than 6 weeks since prior monoclonal antibodies
• Prior allogeneic or autologous bone marrow transplant allowed provided the following criteria are met:

• More than 90 days since transplant
• No acute graft-versus-host disease (GVHD) ≥ grade 2 OR moderate or severe limited chronic GVHD OR extensive chronic GVHD of any severity
• Prior maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, such as, but not limited to, mercaptopurine, thioguanine, or methotrexate allowed
• Concurrent hydroxyurea allowed