Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer
Condition: Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, before
      a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It may
      also stop the patient's immune system from rejecting the donor's stem cells. The donated stem
      cells may replace the patient's immune cells and help destroy any remaining tumor cells
      (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
      infusion) after the transplant may help increase this effect. Sometimes the transplanted
      cells from a donor can also make an immune response against the body's normal cells. Giving
      cyclosporine with or without mycophenolate mofetil or methotrexate after the transplant may
      stop this from happening.

      PURPOSE: This phase II trial is studying how well peripheral stem cell transplant works in
      treating patients with metastatic kidney cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the antitumor effect of allogeneic peripheral blood stem cell transplantation
           (PBSCT) in patients with metastatic renal cell carcinoma.

        -  Evaluate the safety and toxicity of a nonmyeloablative, low-intensity, preparative
           regimen followed by an HLA-matched allogeneic PBSCT in these patients.

        -  Determine engraftment by measuring donor-recipient chimerism in lymphoid and myeloid
           lineages in patients treated with this regimen.

        -  Determine the relationship between donor-host chimerism and the incidence of acute and
           chronic graft-versus-host disease in patients treated with this regimen.

        -  Determine the effect of lymphocyte infusions on donor-host chimerism in this patient
           population.

        -  Determine the response rate, disease-free survival, overall survival, and mortality from
           the procedure or tumor progression in patients treated with this regimen.

      OUTLINE:

        -  Nonmyeloablative preparative regimen: Patients receive 1 of 3 preparative regimens prior
           to peripheral blood progenitor cell (PBPC) transplantation. (Regimens 2 and 3 closed to
           accrual as of 10/1/03.)

             -  Regimen 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and
                fludarabine IV over 30 minutes on days -5 to -1.

             -  Regimen 2 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV
                over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1, and
                antithymocyte globulin on days -5 to -2.

             -  Regimen 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV
                over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and
                antithymocyte globulin on days -5 to -2.

        -  PBPC transplantation: Patients undergo mobilized CD34+ PBPC transplantation on day 0.
           PBPC transplantation may be repeated on days 1 and 2, if deemed necessary.

        -  Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of 3 GVHD prophylaxis
           regimens.

             -  Regimen 1 (closed to accrual as of 10/17/00): Patients receive cyclosporine IV over
                12 hours or orally beginning on day -4 and continuing for up to approximately 3
                months.

             -  Regimen 2 (open to accrual from 10/17/00 through 2/11/02): Patients receive
                cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil.

             -  Regimen 3 (open to accrual as of 2/11/02): Patients receive cyclosporine as in
                regimen 1. Patients also receive methotrexate.

        -  Donor lymphocyte infusions: Patients with progressive disease on days 15-30, day 60, or
           day 100, without GVHD, receive infusion(s) of donor lymphocytes. Further donor
           lymphocyte infusions after day 100 may be given at the discretion of the attending
           physician.

      Patients are followed every 2 months for 6 months, every 3 months for 2 years, and then every
      6 months for 2½ years.

      PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
    

Intervention name(s): HLA Matched Peripheral BLood Stem Cells
Intervention type(s): Other
Intervention description(s): Cell Product
Intervention model: Single Group Assignment
Intervention model description: patients with progressive metastatic renal cell carcinoma.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV renal cell cancer; recurrent renal cell cancer