S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

OBJECTIVES:

• To test whether the complete remission (CR) rate (CR and incomplete CR) in adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia is sufficiently high after treatment with cytarabine, clofarabine, and epratuzumab to warrant further investigation.
• To estimate the frequency and severity of toxicities associated with the dosing schedule of cytarabine, clofarabine, and epratuzumab used in this study.
• To investigate, preliminarily, the effect of laboratory correlates (minimal post-treatment residual disease) and cytogenetic factors on prognosis in this patient population. (Not reported here due to limited MRD data)

OUTLINE: This is a multicenter study.

Patients receive cytarabine IV over 2 hours on days 1-5, clofarabine IV over 1 hour on days 2-6, and epratuzumab IV over at least 1 hour on days 7, 14, 21, and 28 in the absence of disease progression or unacceptable toxicity*.

NOTE: * Prophylactic intrathecal methotrexate is required for patients < 22 years of age, and is recommended (but not required) for patients ≥ 22 years of age.

Blood samples, bone marrow samples, and/or tumor tissue samples may be collected for further laboratory analysis.

Patients are followed up every 3 months for 2 years, then annually for 3 years (until 5 years after registration).

DISEASE CHARACTERISTICS:

• Morphologically confirmed precursor B-cell acute lymphoblastic leukemia (ALL) (non T-cell)

• Must have evidence of disease in bone marrow or peripheral blood

• Immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell)
• Must have ≥ 5% lymphoblasts present in the blood or bone marrow
• At least 20% of marrow and/or peripheral blood lymphoblasts must be CD22+ by flow cytometry

• Co-expression of myeloid antigens (CD13 and CD33) allowed
• Patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible
• Philadelphia (Ph) chromosome-negative disease

• Patients with unknown Ph status by cytogenetics or FISH and unknown BCR/ABL status by PCR are eligible for study registration, but must be removed from study therapy if found to be Ph+ or BCR/ABL+ after study registration
• Refractory to a standard induction regimen that included vincristine and prednisone or high-dose cytarabine or mitoxantrone OR relapsed after successful prior induction therapy

• Any number of prior induction therapies or any number of remissions achieved are allowed
• No M0 acute myeloid leukemia, mixed lineage leukemia, or L3 (Burkitt) leukemia
• No active CNS involvement by clinical evaluation

• Patients with a documented history of CNS involvement of ALL or with clinical signs or symptoms consistent with CNS involvement of ALL must undergo a lumbar puncture that is negative for CNS involvement of ALL
• Patients < 22 years of age must be willing to receive prophylactic intrathecal chemotherapy
• Must be registered on SWOG-9007 "Cytogenetic Studies in Leukemia Patients" (closed as of 07/01/2010)

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Serum creatinine ≤ 1.0 mg/dL OR glomerular filtration rate > 60 mL/min
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• HIV-positive patients are eligible (at the discretion of the investigator) provided the following criteria are met:

• No history of AIDS-defining conditions
• CD4 cell count > 350/mm³
• If on antiretroviral agents, must not include zidovudine or stavudine
• Willing to receive prophylaxis for pneumocystis jirovecii pneumonia during study therapy (regardless of CD4 cell count) until the CD4 cell count is > 200/mm³ after completion of study treatment
• Prior malignancy (other than ALL) allowed provided it is in remission and there are no plans to treat the malignancy at the time of study registration
• No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as exhibiting ongoing signs or symptoms related to the infection with no improvement despite appropriate antibiotics or other treatment
• No neuropathy (cranial, motor or sensory) ≥ grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Any number of prior therapies allowed
• More than 90 days since prior allogeneic bone marrow transplant (BMT)

• No concurrent immunosuppression therapy for the treatment of graft-vs-host disease (GVHD)
• No acute GVHD ≥ grade 2, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity
• Prior autologous BMT allowed

• No concurrent immunosuppression therapy for the treatment of GVHD
• More than 14 days since prior chemotherapy, investigational agents, or major surgery and recovered

• Maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, including but not limited to, mercaptopurine, thioguanine, and methotrexate allowed
• Concurrent hydroxyurea to reduce WBC to a reasonable level (as deemed by the treating physician) allowed
• No prior clofarabine or epratuzumab
• No other concurrent cytotoxic therapy or investigational therapy
• No concurrent alternative medications (e.g., herbal or botanical medications for anticancer purposes)
• Concurrent participation on SWOG-S9910 "Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary" allowed (closed as of 07/01/2010)