T-Cells Transduced With Either CXCR2 or Nerve Growth Factor Receptor (NGFR)
The goal of this clinical research study is to learn the side effects of T-cells injected with CXCR2 and NGFR when given in combination with chemotherapy (cyclophosphamide and fludarabine) and aldesleukin to patients with metastatic melanoma in an attempt to allow them to better localize the tumor. The safety of this combination will also be studied.
T cells are types of white blood cells that help your body fight infections. T-cells are designed to recognize and kill melanoma cells. Researcher want to grow your T-cells in a laboratory, inject them with CXCR2 and NGFR to be able to recognize tumor cells, and then give them back to you. 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
Procedure: T cell Infusion
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Lymphodepletion Plus Adoptive Cell Transfer With T-Cells Transduced With CXCR2 and Nerve Growth Factor Receptor (NGFR) Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma|
- Toxicity of CXCR2 Transduced Tumor Infiltrating Lymphocytes (TIL) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Study will utilize National Cancer Institute Common Terminology Criteria (CTC) for Adverse Events version 4.0 for toxicity and Adverse Event reporting. Toxicity, immunologic effects and anti-tumor efficacy of cell infusions will be performed. Toxicities monitored and documented on a daily basis beginning at day 0 (T-cell infusion) and continuing until discharged from hospital following the initial IL-2 infusion. Maximum tolerated dose (MTD) defined as dose having posterior mean probability to toxicity closest to the targeted value .20.
- Tumor Response [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]Primary clinical endpoint response defined following immune-related response criteria as 50% or greater decrease in tumor's linear dimension post treatment, compared to baseline. Immunological endpoints include (i) at infusion, Xc = number of CXCR2 transduced cells and Xs = number of NGFR transduced (control) cells, (ii) post treatment, based on tumor biopsy, Yc = number of CXCR2 transduced cells and Ys = number of NGFR transduced cells, and (iii) post treatment, ZCXCR2 = amount of CXCR2 cytokine and ZCXCR8 = amount of CXCL8 (IL-8) cytokine.
|Study Start Date:||April 2014|
|Estimated Primary Completion Date:||April 2019 (Final data collection date for primary outcome measure)|
Experimental: CXCR2 + NGFR T-cells
Cytoxan administered intravenously (IV) at 60 mg/kg/day over approximately 2 hours on Days -7 and -6. Mesna 60 mg/kg administered IV over 24 hours on Days -7 and -6. Fludarabine infused at 25 mg/m2 IV daily over approximately 15-30 minutes on Days -5 to -1. On day 0, all patients receive up to 1.5x10^11 T cells (including both CXCR2 and NGFR transduced TIL). TIL infused as an inpatient by IV over approximately 15-60 minutes. Twelve (12) to sixteen (16) hours after completing T cell infusion, all patients receive high dose interleukin-2 (IL-2) on an inpatient basis at 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, as tolerated.
60 mg/kg/day by vein on Days -7 and -6.
Other Names:Drug: Mesna
60 mg/kg by vein on Days -7 and -6.
Other Name: MesnexDrug: Fludarabine monophosphate
25 mg/m2 by vein on Days -5 to -1.
Other Names:Procedure: T cell Infusion
Participants receive up to 1.5x10^11 T cells by vein (including both CXCR2 and NGFR transduced TIL) on Day 0.Drug: IL-2
720,000 IU/kg by vein every 8-16 hours for up to 15 doses on Days 1 to 5.
Other Names:Other: Questionnaire
Questionnaire completion about health and quality of life one (1) time a year for up to 15 years. Questionnaire should take about 15 minutes to complete.
Other Name: Survey
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|Contact: Patrick Hwu, MD||713-792-2921|
|United States, Texas|
|UT MD Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Patrick Hwu, MD||UT MD Anderson Cancer Center|