Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy and kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy plus peripheral stem cell transplantation in treating patients with metastatic melanoma.
|Stage IV Melanoma Recurrent Melanoma||Drug: allogeneic lymphocytes Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: fludarabine||Phase 1 Phase 2|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||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|
|Study Start Date:||January 1999|
|Study Completion Date:||October 2002|
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.
A total of 40 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003552
|United States, Maryland|
|National Heart, Lung, and Blood Institute|
|Bethesda, Maryland, United States, 20892|
|Study Chair:||Richard W. Childs||National Heart, Lung, and Blood Institute (NHLBI)|