Phase I Study of In Vivo Expansion of Melan-A/MART-1 Antigen-Specific CD8 T Lymphocytes Following Transient Immunosuppression in Patients With Advanced Melanoma
- Determine the magnitude and duration of the expansion of antigen-specific T-cells
present in post-vaccination peripheral blood mononuclear cells and reinfused after
immunosuppression in patients with metastatic melanoma.
- Characterize the T-cell subsets (phenotype, function, T-cell receptor repertoire) in
- Determine the tumor response in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is an open-label dose-finding study. Patients undergo leukapheresis to collect
whole peripheral blood mononuclear cells (PBMC). Patients are then assigned to 1 of 3
- Group 1 (closed to accrual as of 5/8/2007): Patients receive cyclophosphamide IV on
days -7 and -6 and fludarabine IV on days -5 to -3. Patients undergo autologous PBMC
infusion on day 0. Patients also receive vaccination comprising Melan-A vaccine
emulsified in incomplete Freund's adjuvant (IFA) subcutaneously (SC) once every 3 weeks
beginning on day 0.
- Group 2 (closed to accrual as of 8/15/2007): Patients receive cyclophosphamide IV at a
higher dose than in group 1 on days -7 and -6 and fludarabine IV on days -5 to -3.
Patients also receive an autologous PBMC infusion and Melan-A vaccine emulsified in IFA
as in group 1.
- Group 3: Patients receive cyclophosphamide IV at 30 mg/kg on days -7 and -6. Patients
also receive fludarabine 30 mg/m2 IV on days -5 to -3, autologous PBMC infusion on day
0,and Melan-A vaccine emulsified in IFA and IMP321. The first 3 patients receive 25
micrograms of IMP321, in the absence of severe 3 or 4 toxicity, the dose will be
escalated to IMP321 250 micrograms.
PROJECTED ACCRUAL: A total of 9 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phenotype, function, and T-cell receptor repertoire
Anti-tumor immune response evaluated at each vaccine and until the last administered vaccine
Serge Leyvraz, MD
Centre Hospitalier Universitaire Vaudois