Cellular Adoptive Immunotherapy in Treating Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Cellular adoptive immunotherapy uses a person's white blood cells that are treated
      in the laboratory to stimulate the immune system in different ways and stop cancer cells from
      growing. Rituximab and fludarabine may also prevent the body from making an immune response
      against the laboratory-treated white blood cells that are put back into the body.
      Interleukin-2 may help the laboratory-treated white blood cells stay in the body longer.
      Giving cellular adoptive immunotherapy together with rituximab, fludarabine, and
      interleukin-2 may kill more cancer cells.

      PURPOSE: This phase I trial is studying the side effects of cellular adoptive immunotherapy
      in treating patients with relapsed or refractory follicular non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety and feasibility of cellular adoptive immunotherapy using autologous
           cytotoxic T lymphocytes genetically modified to express a CD19-specific chimeric
           immunoreceptor gene and HyTK selection/suicide gene in patients with relapsed or
           refractory follicular non-Hodgkin's lymphoma.

      Secondary

        -  Determine the in vivo persistence of adoptively transferred cytolytic T cells in
           patients treated with lymphodepleting therapy comprising rituximab and fludarabine.

        -  Assess the development of host immune responses against the CD19-specific chimeric
           immunoreceptor gene and/or HyTK selection/suicide gene.

        -  Determine the safety of low-dose interleukin-2 in supporting in vivo persistence of
           adoptively transferred cytotoxic T cells.

        -  Determine the anti-tumor activity of this regimen in these patients.

      OUTLINE: This is a nonrandomized, open-label, pilot study.

        -  Leukapheresis: Patients undergo leukapheresis for collection of peripheral blood
           mononuclear cells (PBMCs). CD3-positive cytotoxic T lymphocytes (CTLs) are isolated and
           genetically modified to express a CD19-specific chimeric immunoreceptor and the HyTK
           fusion protein, and are then expanded in vitro.

        -  Lymphodepleting therapy: Patients receive rituximab and fludarabine prior to T-cell
           infusions.

        -  Cellular adoptive immunotherapy and interleukin-2 (IL-2): Patients receive a total of 5
           infusions of genetically modified autologous T cells. Patients may receive low-dose IL-2
           subcutaneously after infusions 3, 4, and 5.

        -  Additional IL-2 therapy: After the completion of the last T-cell infusion, patients with
           evidence of adoptively transferred T cells may receive additional IL-2.

      After completion of study treatment, patients are followed periodically for approximately 65
      days and then annually for at least 15 years.

      PROJECTED ACCRUAL: At least 5 patients will be accrued for this study within 3 years.
    

Intervention name(s): aldesleukin; rituximab; therapeutic autologous lymphocytes; fludarabine phosphate
Intervention type(s): Biological; Biological; Biological; Drug
Intervention MeSH terms: Aldesleukin; Rituximab; Fludarabine; Fludarabine phosphate
Allocation: Non-Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma