S0910, A Phase II Study of Epratuzumab (NSC-716711) in Combination With Cytarabine and Clofarabine for Patients With Relapsed or Refractory Ph- Negative Precursor B-Cell Acute Lymphoblastic Leukemia

Inclusion Criteria

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)