Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma
Condition: Infection; Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell
      transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy
      drugs and kill more cancer cells. Biological therapies use different ways to stimulate the
      immune system and stop cancer cells from growing.

      PURPOSE: Randomized phase I/II trial to study the effectiveness of combining chemotherapy
      with peripheral stem cell transplantation followed by immunotherapy in treating patients who
      have multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the feasibility of expanding ex vivo autologous T cells and infusing these
           cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in
           patients with multiple myeloma.

        -  Determine the response rate and progression-free survival of patients who receive
           anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100
           post-transplantation.

        -  Compare response and survival rates of these patients to historical controls.

        -  Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an
           anti-pneumococcal immune response post-transplantation in these patients.

        -  Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem
           cell graft results in an earlier and/or enhanced immune response than with a graft
           containing "non-educated" APCs in these patients.

        -  Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo
           contributes to the anti-pneumococcal immune response in these patients.

      OUTLINE: This is a randomized, multicenter study.

      Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF)
      subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect
      mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs). ATCs
      are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells.

      Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and
      melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1
      only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on
      day 1 and continuing until blood counts recover.

      Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4
      treatment arms.

        -  Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before
           lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs
           IV over 20-60 minutes around day 12-14 post-transplantation.

        -  Arm II: Patients receive PCV as in arm I but receive ATCs around day 100
           post-transplantation.

        -  Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs as
           in arm I.

        -  Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose
           not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation.

      All patients are offered standard pneumococcal polysaccharide vaccine at 12 months.

      Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months,
      and then every 3 months thereafter.

      PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14 months.
    

Intervention name(s): filgrastim; pneumococcal polyvalent vaccine; therapeutic autologous lymphocytes; therapeutic tumor infiltrating lymphocytes; carmustine; cyclophosphamide; melphalan; bone marrow ablation with stem cell support; peripheral blood stem cell transplantation
Intervention type(s): Biological; Biological; Biological; Biological; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Cyclophosphamide; Melphalan; Carmustine; Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Randomized
Primary purpose: Treatment
Keywords: infection; refractory multiple myeloma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma