Combination Chemotherapy Followed By Autologous Stem Cell Transplant, and White Blood Cell Infusions in Treating Patients With Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and
      melphalan work in different ways to stop the growth of cancer cells, either by killing the
      cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy)
      may kill more cancer cells. A peripheral stem cell transplant may be able to replace
      blood-forming cells that were destroyed by chemotherapy. Giving white blood cells, that have
      been treated in the laboratory with antibodies, may make the transplant work better. Giving
      combination chemotherapy followed by an autologous stem cell transplant, and white blood cell
      infusions may be an effective treatment for non-Hodgkin's lymphoma.

      PURPOSE: This phase I trial is studying the side effects and best dose of white blood cell
      infusions when given together with combination chemotherapy, and autologous stem cell
      transplant in treating patients with non-Hodgkin's lymphoma that has relapsed, is refractory,
      or is in remission.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the toxicity of high-dose combination chemotherapy comprising
           cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood stem
           cell transplantation and immunotherapy consolidation therapy comprising anti-CD3 x
           anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC) in patients with
           non-Hodgkin's lymphoma.

        -  Determine the maximum tolerated dose of CD20Bi-ATC in patients treated with this
           regimen.

        -  Determine whether ATC traffic to tumor sites in select patients treated with this
           regimen.

        -  Assess the immune reconstitution of B cells and incidence of infection in patients
           treated with this regimen.

        -  Compare relapse rates and overall survival of patients treated with this regimen with
           historical controls.

      OUTLINE: This is a dose-escalation study of activated T cells.

        -  Peripheral blood stem cell (PBSC) mobilization and collection: Patients receive
           filgrastim (G-CSF) subcutaneously (SC) once daily for 5 days. They then undergo
           leukaphereses to collect peripheral blood stem cells (PBSC). Some of the lymphocytes are
           treated in the laboratory to produce anti-CD3 x anti-CD20 bispecific antibody
           (CD20Bi)-activated T cells (ATC).

        -  High-dose chemotherapy and PBSC transplantation: Patients receive carmustine IV on day
           -7, etoposide IV twice daily and cytarabine IV twice daily on days -6, -5, -4, and -3,
           and melphalan IV on day -2. Autologous PBSC are reinfused on day 0.

        -  Immunotherapy consolidation: Patients receive immunotherapy consolidation comprising
           CD20Bi-ATC IV over 15-30 minutes starting on day 4, once a week for 4 weeks for a total
           of four infusions.

      Cohorts of 3-6 patients receive escalating doses of CD20Bi-ATC until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
      of 6 patients experience dose-limiting toxicity.

      After completion of study treatment, patients are followed periodically for survival.

      PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.
    

Intervention name(s): therapeutic autologous lymphocytes; carmustine; cytarabine; etoposide; melphalan; peripheral blood stem cell transplantation (PBSCT)
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection
Intervention MeSH terms: Cytarabine; Etoposide; Melphalan; Carmustine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 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; stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; recurrent small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma