A Pilot Study of the Administration of Young Tumor Infiltrating Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic
melanoma when administered to the autologous patient along with high-dose aldesleukin
(IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
- IL-2 administration has been shown to increase the number of T regulatory cells and in
our trials we have found a direct relationship between the number of IL-2 doses and the
reconstitution of patients at one week with CD4+ Foxp3+ T regulatory cells.
- In our analysis of factors that relate to the ability of this treatment to mediate
objective responses, we have found a highly significant inverse correlation between
reconstitution of CD4+ Foxp3+ T regulatory cells and the likelihood of achieving an
- In our prior clinical trials of cell transfer using TIL after lymphodepletion with or
2Gy total body irradiation, patients who experienced an objective response received
fewer doses of IL-2 compared to non-responders (p=0.007 and 0.03 respectively).
- High levels of the homeostatic T cell growth factor, IL-15, are present in patient
serum after the lymphodepleting regimen at the time of cell transfer.
- These factors raise the possibility that IL-2 administration is not required after cell
- The primary objective of this trial is to determine whether objective responses can be
mediated in patients with metastatic melanoma who have received a lymphodepleting
chemotherapy regimen and adoptive transfer of young tumor infiltrating lymphocytes and
no IL-2 administration.
- The secondary objective involves the determination of the level of transferred cells in
the blood that persist at about 1 week and 1 month after transfer.
- Patients greater than or equal to 18 years old with pathologically confirmed diagnosis
of metastatic melanoma.
- Patients with measurable disease, absolute neutrophil count greater than 1000/mm(3) and
platelet count greater than 100,000/mm(3).
- Patients not eligible to receive IL-2 because of cardiovascular or respiratory problems
or who refuse IL-2.
- Patients with metastatic melanoma will undergo resection to obtain tumor for generation
of autologous TIL cultures.
- Patients will receive a non-myeloablative lymphodepleting preparative regimen
consisting of cyclophosphamide and fludarabine followed by the administration of young
- Patients will be evaluated for objective clinical response and for persistence of the
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine whether objective responses can be mediated in patients with metastitic melanoma who have received a lymphodepleting chemotherapy regimen and adoptive transfer of young tumor infiltrating lymphocytes and no IL-2 administration.
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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