Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Condition: Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Waldenstrom Macroglobulinemia; Lymphoma, Large-Cell, Anaplastic; Recurrence
Intervention: cyclophosphamide; etoposide; iodine I 131 tositumomab; quality-of-life assessment; peripheral blood stem cell transplantation
Intervention description: Given IV; Given IV; Given IV; Ancillary study; Undergo ASCT given via central catheter
Intervention MeSH terms: Iodine; Cadexomer iodine; Cyclophosphamide; Etoposide; Etoposide phosphate; Tositumomab I-131; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 111.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving iodine I 131 tositumomab together with
      etoposide and cyclophosphamide followed by autologous stem cell transplant works in treating
      patients with relapsed or refractory non-Hodgkin's lymphoma. Radiolabeled monoclonal
      antibodies, such as iodine I 131 tositumomab, can find cancer cells and deliver radioactive
      cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy,
      such as etoposide and cyclophosphamide, work in different ways to stop the growth of cancer
      cells, either by killing the cells or by stopping them from dividing. Combining a
      radiolabeled monoclonal antibody with combination chemotherapy before autologous stem cell
      transplant may kill more cancer cells
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of lymphoma expressing the
             cluster of differentiation (CD)20 antigen and generally must have failed at least one
             prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL)
             patients, who may be enrolled while in first complete remission (CR) in accordance
             with current transplant standard of care for these patients

          -  Note: Patients with clinically non-transformed follicular lymphomas do not require
             repeat biopsies for immunophenotyping since these tumors are uniformly reactive with
             the tositumomab antibody

          -  Patients must have tumor burdens < 500cc by computed tomography (CT) or magnetic
             resonance (MRI) volumetric measurements and must not have splenomegaly at the time of
             enrollment; splenomegaly will be defined as a spleen volume > 2 standard deviations of
             the mean spleen volume to body weight ratio (mean = 3.84 cc/kg, SD = 1.53 cc/kg);
             thus, patients with > 6.9cc/kg will be defined as having splenomegaly; patients with
             splenomegaly that is thought to be due to G CSF/GM-CSF effect and not due to
             lymphomatous involvement of the spleen can been deemed eligible with the approval of
             an investigator

          -  Patients must have normal renal function (creatinine [Cr] < 2.0)

          -  Patients must have normal hepatic function (bilirubin < 1.5mg/dL), with the exception
             of patients thought to have Gilbert's syndrome, who may have a total bilirubin above
             1.5mg/dL

          -  All patients eligible for therapeutic study must have autologous hematopoietic stem
             cells (2 x 10^6 CD34+ cells/kg) harvested and cryopreserved

          -  Patients must have an expected survival of > 60 days and must be free of major
             infection

        Exclusion Criteria:

          -  Circulating anti-mouse antibody (HAMA)

          -  Systemic anti-lymphoma therapy given within 30 days prior to anticipated treatment
             date

          -  Inability to understand or give an informed consent

          -  Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord,
             or over 25% of red marrow)

          -  Central nervous system lymphoma

          -  Other serious medical conditions considered to represent contraindications to
             autologous stem cell transplant (ASCT) (e.g., active coronary artery disease,
             pulmonary dysfunction [forced expiratory volume in 1 second (FEV1) < 70% expected,
             Vital Capacity < 70% expected, diffusing capacity of the lung for carbon monoxide
             (DLCO) < 50%, patient on supplemental oxygen], AIDS, etc.)

          -  Pregnancy

          -  Prior bone marrow or stem cell transplant

          -  Presence of circulating lymphoma cells by morphology or flow cytometry (>= 0.1%) at or
             near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSC are to
             be used

          -  Southwest Oncology Group (SWOG) performance status >= 2.0

          -  Unable to perform self-care during radiation isolation

          -  Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well
             differentiated lymphocytic lymphoma (ineligible because these tumors express very low
             surface densities of CD20)