Trial Information

Phase I/II Study of HLA-Matched Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation Followed by Allogeneic T-cell Infusion as Adoptive Immunotherapy in Patients With Metastatic Melanoma

OBJECTIVES: I. Identify an antitumor effect of allogeneic peripheral blood stem cell
transplantation (PBSCT) in patients with metastatic melanoma.

II. Evaluate the safety and toxicity of a nonmyeloablative, low intensity, preparative
regimen followed by an HLA-matched allogeneic PBSCT in these patients.

III. Monitor engraftment by measuring donor-recipient chimerism in lymphoid and myeloid
lineages in these patients.

IV. Investigate the relationship between donor-host chimerism and the incidence of acute
and chronic graft-versus-host disease in this patient population.

V. Investigate the effect of lymphocyte infusions on donor-host chimerism in this patient
population.

VI. Determine disease-free survival, overall survival, and mortality from the procedure or
tumor progression in this patient population.

PROTOCOL OUTLINE: This is a dose-escalation study of a conditioning regimen. Patients
receive 1 of 3 dose levels of chemotherapy prior to peripheral blood progenitor cell (PBPC)
transplantation. Patients at dose level 1 receive cyclophosphamide IV over 1 hour on days
-7 and -6 and fludarabine IV over 30 minutes daily on days -5 to -1. Patients at dose level
2 receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine IV over 30 minutes
daily on days -5 to -1, and antithymocyte globulin daily on days -5 to -2. Patients at dose
level 3 receive cyclophosphamide IV over 1 hour daily on days -8 to -6, fludarabine IV over
30 minutes daily on days -5 to -1, and antithymocyte globulin daily on days -5 to -2.

Patients undergo mobilized CD34+ PBPC transplantation on day 0. PBPC transplantation may
be repeated on days 1 and 2 if deemed necessary.

Patients with progressive disease on days 15-30, day 60, or day 100, without
graft-versus-host disease, 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 the next 2 years, and
then every 6 months until year 5 posttransplantation.

PROJECTED ACCRUAL:

A total of 40 patients will be accrued for this study.