S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: epratuzumab; clofarabine; cytarabine; laboratory biomarker analysis
Intervention MeSH terms: Cytarabine; Clofarabine; Epratuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 16 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: B-cell adult acute lymphoblastic leukemia; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia

Summary:

      RATIONALE: Monoclonal antibodies, such as epratuzumab, can block cancer growth in different
      ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and
      help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such
      as cytarabine and clofarabine, work in different ways to stop the growth of cancer cells,
      either by killing the cells or by stopping them from dividing. Giving epratuzumab together
      with cytarabine and clofarabine may kill more cancer cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving epratuzumab
      together with cytarabine and clofarabine works in treating patients with relapsed or
      refractory acute lymphoblastic leukemia.
    

Eligibility 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)