Monoclonal Antibody Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplant in Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver
      cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy
      use different ways to stop cancer cells from dividing so they stop growing or die. Combining
      chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses
      of chemotherapy drugs and kill more cancer cells.

      PURPOSE: This phase II trial is studying how well monoclonal antibody therapy, chemotherapy,
      and peripheral stem cell transplant work in treating patients with relapsed or refractory
      non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the response rates and time to treatment failure in patients with relapsed or
           refractory non-Hodgkin's lymphoma treated with iodine I 131 monoclonal antibody anti-B1,
           followed by high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM), and
           autologous peripheral blood stem cell transplantation (APBSCT) vs historical control
           patients treated with high-dose BEAM or carmustine, etoposide, cytarabine, and
           cyclophosphamide and APBSCT.

        -  Determine the safety of this regimen in these patients.

      OUTLINE: Autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+
      cells or granulocyte macrophage colony-forming units. On day -19, patients receive unlabeled
      monoclonal antibody anti-B1 (MOAB anti-B1) IV followed by a dosimetric dose of iodine I 131
      MOAB anti-B1 IV over 20 minutes. On day -12, patients receive unlabeled MOAB anti-B1 IV
      followed by a therapeutic dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. Patients then
      receive high-dose chemotherapy comprising carmustine IV on day -6, etoposide IV and
      cytarabine IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo
      autologous PBSC transplantation on day 0.

      Patients are followed at days 30 and 100, at 6 months, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 5 years.
    

Intervention name(s): carmustine; cytarabine; etoposide; melphalan; peripheral blood stem cell transplantation; tositumomab and iodine I 131 tositumomab
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): 300 mg/m2 IV on Day -6; 100 mg/m2 BID on Days -5 through -2; 100 mg/m2 BID on Days -5 through -2; 140 mg/m2 IV on Day -1; Following the chemotherapy, on Day 0 of treatment, the previously stored hematopoietic stem cells will be administered to the patient intravenously through a central line to the patient.; Patients will receive two administrations of Iodine-131 Anti-B1 Antibody; the "dosimetric dose" and the "therapeutic dose". The dosimetric dose will consist of an infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by an infusion of Anti-B1 Antibody (35 mg) which has been trace labeled with 5 mCi of Iodine-131 Anti-B1 Antibody. Using whole body anterior and posterior gamma camera scans and serial imaging studies over approximately one week, the clearance of the whole body dosimetric dose will be used to calculate the subsequent therapeutic dose of Iodine-131 Anti-B1 Antibody which delivers a total body dose of 75 cGy to the subject
Other intervention name(s): BCNU; cytosine arabinoside; Etopophos, Toposar; Evomela; Autologous Hematopoietic Stem Cell Transplantation; Iodine-131 Anti-B1 Antibody
Intervention MeSH terms: Iodine; Cytarabine; Etoposide; Melphalan; Carmustine; Tositumomab I-131
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma