Clinical Trial: 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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Participant

Brief Summary:

This is a pilot study to assess the feasibility and safety of producing sufficient quantities 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.


Detailed Summary:

15 patients will be treated. Patients will receive T-cells transduced with DNRII as well as T- cells transduced with NGFR (as a control gene).

All participants will receive the same dose level of cyclophosphamide, fludarabine, and aldesleukin.

Study Drug Administration:

The days leading up to Day 1 of the study are considered negative days. For example, the day before Day 0 is Day -1. Day 0 is when you will receive the T-cells, as explained below.

On Days -7 and -6, you will receive cyclophosphamide by vein over about 2 hours. You will also receive furosemide by vein over about 60 minutes to try to increase the amount of urine your body makes.

On Day -7, you will receive mesna by vein non-stop over about 24 hours. Mesna is given to help protect the bladder from side effects of cyclophosphamide.

You will take trimethoprim and sulfamethoxazole (SMX) by mouth 2 times a day, starting on Day -7 and continuing for at least 6 months after chemotherapy. SMX is given to lower your risk of side effects.

On Days -5 to -1, you will receive fludarabine by vein over about 15-30 minutes.

On Day 0, you will receive TGFb-DNR and NGFR T-cells through a central venous catheter (CVC) for up to 4 hours, or possibly more if your doctor thinks it is needed. A CVC is a thin flexible tube that is inserted into the body. The catheter may be placed into a vein in your arm or in a large vein in your neck. If the cells need to be given through a large vein in your upper chest or in your neck, the area will be numbed with anesthetic before the catheter is pu
Sponsor: M.D. Anderson Cancer Center

Current Primary Outcome: 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.


Original Primary Outcome: Maximum Tolerated Dose (MTD) [ Time Frame: 6 weeks ]

Maximum Tolerated Dose (MTD) defined as the dose having posterior mean probability to toxicity closest to the targeted value .20.


Current Secondary Outcome: 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.


Original Secondary Outcome:

Information By: M.D. Anderson Cancer Center

Dates:
Date Received: September 27, 2013
Date Started: October 2014
Date Completion:
Last Updated: December 12, 2016
Last Verified: December 2016