Prospective Randomized Comparative Study of Cell Transfer Therapy Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Compared to High-dose Aldesleukin 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.
- Although this adoptive cell therapy (ACT) has been shown capable of mediating objective
clinical responses in patients with metastatic melanoma, including patients who have
previously been treated with aldesleukin or chemotherapy, the treatment is only
available in the Surgery Branch, National Cancer Institute (NCI) and in just one or two
other institutions in the United States.
- Despite our reports of the objective regressions in patients receiving adoptive cell
therapy (ACT), doubts have been raised concerning the possible influence of patient
selection bias that may have accounted for the increase in survival using ACT compared
to historical controls.
- ACT is a cumbersome and labor intensive procedure which has discouraged many from
applying it. We have recently developed simplifications in the technique for generating
TIL that are also capable of mediating objective responses.
- To evaluate the efficacy of ACT we are now proposing a prospective randomized trial to
compare this form of therapy with standard available treatment for patients with
- To determine, in a prospective randomized trial, the response rate and progression free
survival of patients with metastatic melanoma receiving either ACT or standard
high-dose aldesleukin treatment.
- Survival rate will be evaluated as a secondary endpoint.
- To determine the toxicity of these two treatment regimens.
Patients who are 18 years of age or older must have:
- Evaluable metastatic melanoma;
- No prior treatment with high-dose aldesleukin (greater than or equal to 600,000 IU IL-2
q8h or the equivalent)
- No contraindications to high-dose aldesleukin administration;
- No concurrent major medical illnesses or any form of immunodeficiency;
- Lesions of at least 2cm in diameter that can be surgically removed with minimal
- Prior to amendment D, patients with metastatic melanoma lesions that can be resected
with minimal morbidity will be prospectively randomized to receive either ACT using
CD8+ young TIL (arm 2) and aldesleukin (arm 1) following a non-myeloablative
chemotherapy preparative regimen, or will receive standard high-dose aldesleukin
- With the approval of amendment D, arm 1 and 2 will be closed, and two new arms will be
opened. Patients with metastatic melanoma lesions that can be resected with minimal
morbidity will be prospectively randomized to receive either ACT using young TIL (arm
4) and aldesleukin (arm 3) following a non-myeloablative chemotherapy preparative
regimen, or will receive standard high-dose aldesleukin therapy.
- Response rate and time to progression will be evaluated for all patients on an
- Patients may crossover to the other treatment arm after progressive disease is
documented by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, if still
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Ramaprasad Srinivasan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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