Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)
- Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate
the regression of bulky metastatic melanoma when administered along with high-dose
aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy
preparative regimen consisting of cyclophosphamide and fludarabine.
- In a series of consecutive trials using this chemotherapy preparative regimen alone or
with 2 Gy or 12 Gy total body irradiation (TBI) objective response rates using RECIST
criteria were 49%, 52%, and 72%, respectively. Complete regression rates in these three
consecutive trials were 12%, 20%, and 40%, respectively-strongly suggesting that the
addition of TBI could improve the complete regression rate. Of the 20 complete
regressions seen in this trial, 19 are on-going at 37 to 82 months.
- Because of the complexity of developing selected TIL for use in adoptive transfer, we
have recently developed a simplified method for producing TIL that is more applicable
to use in outside institutions. Utilizing young TIL cells (sometimes with CD8
purification) in 105 patients, the objective response rate was 34% with a 6.6 %
incidence of complete regressions. All patients in this trial received the
cyclophosphamide fludarabine regimen alone.
- Because of the strong suggestion that the addition of TBI to the chemotherapy regimen
could increase durable, complete regression rates in patients with metastatic melanoma,
we are now attempting to definitively determine whether the addition of TBI to the
chemotherapy preparative regimen can improve complete response rates, and overall
survival in patients receiving young TIL .
- To determine, in a prospective randomized trial, the complete response rate and
survival of patients with metastatic melanoma receiving ACT using young TIL plus
aldesleukin treatment following either a chemotherapy preparative regimen alone, or the
same chemotherapy preparative regimen plus TBI.
- Response rate and progression free survival will be evaluated as a secondary endpoint,
as will the toxicity of these two treatment regimens.
-Patients who are 18 years or older must have:
- Evaluable metastatic melanoma;
- Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL;
- No contraindications to high-dose aldesleukin administration or total body irradiation;
- No concurrent major medical illnesses or any form of immunodeficiency
-Patients with metastatic melanoma will have lesions resected and after TIL growth is
established patients with will be prospectively randomized to receive ACT with young TIL
plus aldesleukin following either a non-myeloablative chemotherapy preparative regimen or
this same regimen plus TBI.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Compare the complete response rate and survival in pts with metastatic melanoma receiving ACT using young TIL plus aldesleukin treatment following either a lymphodepleting chemo or a chemo/total body irradiation preparative regimen.
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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