A Phase II Clinical Trial of Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma
In this study, these special immune T-cells will be taken from a sample of the patient's
tumor tissue that will be surgically removed. Certain parts of these cells will be
multiplied, or grown, in the laboratory. They will then be given back to the patient by an
infusion in their veins. These cells are called tumor infiltrating lymphocytes (TIL). The
investigators want to study the benefits and side effects of TIL when they are given with
the following combination of drugs:
- Vemurafenib - a type of drug used to slow the growth of certain types of cancer cells.
This drug will be given for about three weeks while T-cells are being grown in the lab
and then again after T-cell infusion for up to two years.
- Fludarabine and cyclophosphamide - two types of chemotherapy drugs. These drugs will be
used for what is called lymphodepletion. The purpose of lymphodepletion in this study
is to temporarily reduce the number of normal lymphocytes circulating in the patient's
body before they are given the T-cells that were grown in the lab. This is so that
there will be more "space" for the lymphocytes (T-cells) that will be infused in their
- Interleukin-2 (IL-2) - a drug used to help the body's response to treatment on the
immune system. A high dose regimen of IL-2 will be given after they receive the
infusion of the T-cells.
The use of TIL is investigational, meaning it has not been approved by the U.S. Food and
Drug Administration (FDA). Vemurafenib and IL-2 have been approved by the FDA for the
treatment of metastatic melanoma and melanoma that cannot be surgically removed. The
chemotherapy drugs fludarabine and cyclophosphamide, used for lymphodepletion, have been
approved by the FDA, but not for the treatment of metastatic melanoma.
The combination of vemurafenib followed by lymphodepletion with chemotherapy, TIL infusion,
and high dose IL-2 is investigational, and has not been proven to help treat melanoma. This
combination is not FDA approved; however, the FDA is allowing its use in this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Response (OR)
Overall response (OR) is defined as the patient being alive at week 6, confirmed at week 12 and tumor size evaluated at both times using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 to be a complete response (CR) or partial response (PR). Evaluations will be made by CT scan approximately 6 weeks after the cell infusion, then confirmed by CT scanning approximately 12 weeks after the cell infusion, and by clinical evaluation during the first 12 weeks. The complete response rate, complete and partial response rate (CPR) will be summarized using both a point estimate and its 95% exact confidence interval based on the binomial distribution.
Amod Sarnaik, M.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|