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 Nerve Growth Factor Receptor (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.
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 ]
Phase 1 Toxicity, defined as a grade 3 or 4 non-hematologic toxicity that cannot be resolved therapeutically within 2 weeks of onset, including nausea/vomiting, transaminitis, neutropenia with fever, and thrombocytopenia using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) 4.0 . Toxicities monitored daily basis beginning Day 0 (T-cell infusion) and continuing until discharged from hospital following the initial IL-2 infusion.
Toxicity reporting: a.) Grade 2 or greater allergic reaction and b.) Grade 3 or 4 non-heme toxicities with the exception of: IL-2 expected toxicities; and Toxicities occurring within 24 hours post cell infusion that are reversible to grade 2 or less within 8 hours.
- Tumor Response using Immune-Related Response Criteria (irRC) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]Tumor response defined following immune-related response criteria as 50% or greater decrease in tumor's linear dimension post treatment, compared to baseline using immune-related response criteria (irRC) which is a modified version of World Health Organization (WHO) criteria.
|Study Start Date:||January 2015|
|Estimated Primary Completion Date:||January 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
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01740557
|Contact: Patrick Hwu, MD||713-792-2921|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Patrick Hwu, MD||M.D. Anderson Cancer Center|