Study of Lymphodepletion Plus Adoptive Cell Transfer With TGF-beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Participants With Metastatic Melanoma
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|ClinicalTrials.gov Identifier: NCT01955460|
Recruitment Status : Recruiting
First Posted : October 7, 2013
Last Update Posted : September 13, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: Cyclophosphamide Drug: Mesna Drug: Fludarabine monophosphate Biological: T-Cells Drug: Interleukin-2 (IL-2)||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Lymphodepletion Plus Adoptive Cell Transfer With TGF-beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Participants With Metastatic Melanoma|
|Actual Study Start Date :||October 2014|
|Estimated Primary Completion Date :||October 2019|
|Estimated Study Completion Date :||October 2019|
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 the 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. 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
On day 0, all patients receive the 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.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.
- Feasibility of Producing Sufficient Quantities of TFGâ-DNRII and NGFR Transduced TIL for Treatment of Metastatic Melanoma [ Time Frame: 12 weeks ]Feasibility defined as the production of virally transduced T cells and treatment of patients with these cells. Trial considered successful if the treatment is feasible in at least 12 patients.
- Response of Autologous TGFb Resistant (DNRII Transduced) and NGFR Transduced TIL in Participants with Metastatic Melanoma [ Time Frame: 6 and 12 weeks ]Tumor response to therapy in this study done by using immune-related response criteria (irRC) which is a modified version of WHO criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|