Tumor Infiltrating Lymphocytes (TIL) Transduced With TGFbDNRII
The goal of this clinical research study is to find the highest tolerable dose of T-cells injected with the genes TGFb-DNR and NGFR that can be given in combination with chemotherapy (cyclophosphamide and fludarabine) and aldesleukin to patients with metastatic melanoma.
This study involves gene therapy. T-cells are types of white blood cells that help your body fight infections. They may recognize and kill melanoma cells. Researchers want to grow your T-cells in a laboratory, inject them with TGFb-DNR and NGFR genes which may help them recognize tumor cells, and then give them back to you by vein. This may help to control melanoma.
Cyclophosphamide is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.
Aldesleukin is designed to block the activity of cells that decrease the immune system's ability to fight cancer.
Drug: Fludarabine monophosphate
Drug: Interleukin-2 (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 TGF-Beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma|
- Maximum Tolerated Dose (MTD) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Maximum Tolerated Dose (MTD) defined as the dose having posterior mean probability to toxicity closest to the targeted value .20.
|Study Start Date:||October 2014|
|Estimated Primary Completion Date:||October 2019 (Final data collection date for primary outcome measure)|
Experimental: T-Cells + Chemotherapy
Patients receive T-cells transduced with DNRII as well as T- cells transduced with NGFR (as a control gene). Cytoxan administered at 60 mg/kg/day by vein over approximately 2 hours on Days -7 and -6. Mesna 60 mg/kg by vein over 24 hours on Days -7 and -6. Fludarabine 25 mg/m2 by vein daily over approximately 15-30 minutes on Days -5 to -1. On day 0, all patients receive assigned dose level of transduced DNRII TIL, with an equal number of transduced NGFR TIL, up to a total of 1.5 x 10^11 TIL in NS. Five dose levels of DNRII transduced TIL to be evaluated are 15 x 10^9, 30 x 10^9, 45 x 10^9, 60 x 10^9 and 75 x 10^9 DNRII transduced TIL. Twelve (12) to sixteen (16) hours after completing the T cell infusion, all patients receive high dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 720,000 IU/kg as an intravenous bolus over an approximate 15 minute period every 8-16 hours for up to 15 doses on Days 1 to 5 and 22-26.
60 mg/kg/day by vein on Day -7 and -6.
Other Names:Drug: Mesna
60 mg/kg by vein on Day -7 and -6.
Other Name: MesnexDrug: Fludarabine monophosphate
25 mg/m2 by vein on Day -5 to Day -1.
Other Names:Biological: T-Cells
Starting dose level of DNRII transduced TIL T-cells: 15 x 10^9 by vein on Day 0.Drug: Interleukin-2 (IL-2)
720,000 IU/kg by vein every 8-16 hours for up to 15 doses on Days 1 to 5 and 22 to 26.
Other Names:Behavioral: Questionnaires
Quality of life (QOL) questionnaires completed at baseline, 6 and 12 weeks after T-cell infusion, at 6 month follow up, then yearly.
Other Name: Surveys
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01955460
|Contact: Rodabe N. Amaria, MD||713-792-2921|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Rodabe N. Amaria, MD||M.D. Anderson Cancer Center|