Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma
The overall purpose of this research study is to find a better way to treat melanoma. This will be a single arm exploratory trial to evaluate prospectively the feasibility of, the toxicities of, and the persistence of TIL which can survive in vivo.
Drug: Administration of Lymphodepletion
Other: Adoptive Cell Transfer
Drug: High Dose IL-2
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma|
- Number of Participants Who Can Grow and Expand T-Cells [ Time Frame: Average of 10 Months ] [ Designated as safety issue: No ]Feasibility is the primary endpoint of this trial, which is defined as a patient who can grow and expand T-cells. We anticipate that this is feasible for at least 50% of the eligible patients. If it is feasible for seven/six or more patients out of 16 eligible patients, then we will consider to reject a feasibility rate of no more than 25%/20% in favor of at least 50% for a one-sided type I error of 0.08/0.082 and type II error of 0.227/0.105.
- Number of Participants With Objective Response (OR) [ Time Frame: Average of 10 Months ] [ Designated as safety issue: No ]OR is defined as the patient being alive at Day 70 and tumor size evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria to be a complete response (CR) or partial response (PR). Evaluations will be made by computed tomography (CT) scan approximately 6 to 8 weeks after the cell infusion, or CT scan approximately 10 weeks after the cell infusion, or by clinical evaluation during the first 70 days.
- Number of Participants With Adverse Events (AEs) [ Time Frame: Average of 10 Months ] [ Designated as safety issue: Yes ]A 33% or greater rate of unacceptable side effects or death within 30 days of protocol treatment will be sufficient to stop the study for toxicity for the first 12 patients treated on this trial.
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: TIL With High Dose IL-2
Day -7 and -6: Cyclophosphamide 60 mg/kg/day I.V. in 250 ml NS over approximately 2 hours. Mesna 20 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours.
Day -5 to Day -1: Fludarabine 25 mg/m^2 intravenous piggyback (IVPB0 daily over approximately 30 minutes for 5 days.
Day 0: T cell infusion in 250-1000 ml NS over approximately 15-60 minutes depending on volume to be infused.
Days 1-5: High dose IL-2, 720,000 IU/kg IV bolus (about 15 minutes) every 8-16 hours for up to 15 doses, beginning approximately 12-16 hours after T cell infusion.
Surgery to remove a tumor for growth of TIL
Other Names:Drug: Administration of Lymphodepletion
Lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T cell persistence and effectiveness in vivo
Other Name: CytoxanOther: Adoptive Cell Transfer
T-cell infusionDrug: High Dose IL-2
Beginning approximately 12 - 16 hours after cell infusion.
Patients are being offered admission to this study to test the side effects of an investigational treatment prepared from special immune cells (T cells) specific for melanoma. A T-cell is a type of lymphocyte. Lymphocytes are a type of white blood cell that protect people from viral infections; help other cells fight bacterial and fungal infections; produce antibodies; fight cancers; and coordinate the activities of other cells in the immune system. These special immune cells will be taken from a sample of the patient's tumor tissue that will be surgically removed from their body and grown in the laboratory. They will then given back to the patient in their veins. These cells are called tumor infiltrating lymphocytes (TIL). We wish to study the side effects of TIL when they are given with two chemotherapy drugs to temporarily decrease the patient's own immune cells and a drug called Interleukin-2 (IL-2). The two chemotherapy drugs called fludarabine and cytoxan are used to greatly reduce the number of normal lymphocytes circulating in the patient's body, called lymphodepletion, so that there will be more "space" for the cancer fighting lymphocytes (T-cells) that will be infused in their veins. We wish to find out how often these cells can shrink or slow the growth of the patient's melanoma. We also wish to find out the effects of lymphodepletion followed by TIL and high dose IL-2 on the patient's immune system. The lymphodepletion followed by TIL and high dose IL-2 is experimental, and has not been proven to help treat melanoma.
The IL-2 has been approved by the Food and Drug Administration (FDA) for the treatment of metastatic melanoma that cannot be surgically removed. The chemotherapy drugs cytoxan and fludarabine used for lymphodepletion have been approved by the FDA, but not for the treatment of metastatic melanoma.
The combination of lymphodepletion followed by TIL and high dose IL-2 is not FDA approved but the FDA is permitting its use in this study.
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Amod Sarnaik, M.D.||H. Lee Moffitt Cancer Center and Research Institute|