A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
- Determine the ability of treatment with short-term cultured autologous
tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a
nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide
and fludarabine phosphate to mediate tumor regression in patients with metastatic
- Determine the toxicity of this treatment regimen.
- Determine the rate of repopulation of the young TIL cells.
- Establish in vitro immunological correlates that predict in vivo persistence and
- Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and
-6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
- Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients
receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients
also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.
Patients with stable disease, partial response, or recurrent disease after initial response
may receive 1 additional course of treatment (as above) beginning 8 weeks after completion
Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then
periodically thereafter for research studies. Samples are analyzed for differences in
function and phenotype prior to and after TIL infusion. The immunological correlates of
treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow
cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to
determine cell phenotype and function; correlation of in vitro characteristics of the
infused cells with in vivo antitumor activity; and the activity, specificity, and telomere
length using flow FISH.
After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for
1 year, every 6 months for 2 years, and then annually for 2 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.
4-6 weeks after completion of TIL
John P. Hanson, MD
St. Luke's Medical Center
United States: Food and Drug Administration
|Aurora St. Luke's Medical Center||Milwaukee, Wisconsin 53215|