Trial Information

A Phase II Study of HLA-Matched Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation for Metastatic Renal Cell Carcinoma Followed by Allogeneic T-Cell Infusion as Adoptive Immunotherapy

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.