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.
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|