TGF-beta Resistant Cytotoxic T-lymphocytes in Treatment of EBV-positive Nasopharyngeal Carcinoma / RESIST-NPC

NCT02065362 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: H-33954: RESIST-NPCP01CA094237
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Patients have nasopharyngeal carcinoma (NPC). This study is a gene transfer research study using special immune cells. Most patients with NPC show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, suggesting that it may play a role in causing the disease. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called T cells, that have been trained to recognize and kill special parts of EBV infected cells can survive in patient's blood and affect the tumor. We already have given EBV-specific cytotoxic T cells to 30 patients with active NPC and have seen anti-tumor activity in 14 of 30 patients. We are now trying to find out if we can improve this treatment. First, we want to give T cells where more of the cells recognize at least two of the four EBV proteins expressed on NPC cells. We call these cells NPC-specific cytotoxic T cells. Second, we found that T cells work better if we add a receptor to the T cells called DNR (Dominant Negative Receptor). DNR makes T cells resistant to TGFbeta, a factor secreted by cancer cells that helps them escape being killed by the immune system. In this study we will therefore place the DNR gene into NPC-specific T cells (DNR.NPC-specific T cells). In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of patient's lymphocytes first should allow the T cells we infuse to expand and stay longer in their body, and potentially kill cancer cells more effectively. The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used for lymphodepletion in immunotherapy clinical trials.

Conditions

EBV-positive Nasopharyngeal Carcinoma

Keywords

EBV positive; TGFbeta; Nasopharyngeal carcinoma; cytotoxic T lymphocytes

Outcome Measures

Primary Outcomes (1)

• Number of subjects with a dose limiting toxicity

  Determine the safety of escalating doses of intravenous infusions of autologous TGFbeta-resistant NPC-specific cytotoxic T-lymphocytes with lymphodepleting chemotherapy for dose levels 2 and 3 in patients with EBV-positive nasopharyngeal carcinoma (NPC).

  8 weeks

Secondary Outcomes (1)

• Amount of T cells in the blood after the infusions

  15 years

Other Outcomes (1)

• Number of patients with a response to the T cells

  8 weeks

Study Arms (1)

DNR.NPC-specific T cells or DNR.NPC-specific T cells + c/f

EXPERIMENTAL

DNR.NPC-specific T cells or DNR.NPC-specific T cells + c/f

Biological: DNR.NPC-specific T cells; Biological: DNR.NPC-specific T cells + cyclophosphamide + fludarabine

Interventions

DNR.NPC-specific T cells BIOLOGICAL

Each patient will receive 2 infusions, 14 days apart, according to the following dosing schedule: Dose Level 1: Day 0: 2 x 10\^7 cells/m\^2 Day 14: 2 x 10\^7 cells/m\^2 The doses are calculated according to the total T cell number.

DNR.NPC-specific T cells or DNR.NPC-specific T cells + c/f

DNR.NPC-specific T cells + cyclophosphamide + fludarabine BIOLOGICAL

Patients will receive cyclophosphamide and fludarabine for 3 days before receiving the DNR.NPC-specific T cells. Each patient will receive infusions according to the following dosing schedule: Dose Level 2: Cy/Flu on Days -4 to -2 and then 4 x 10\^7 cells/m\^2 on Day 0, Day 1 or Day 2 Dose Level 3: Cy/Flu on Days -4 to -2 and then 1 x 10\^8 cells/m\^2 on Day 0, Day 1, or Day 2

DNR.NPC-specific T cells or DNR.NPC-specific T cells + c/f

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease
• EBV positive tumor
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
• The patient must meet the following eligibility criteria to be included for TREATMENT:
• Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease
• EBV positive tumor
• Patients with life expectancy greater than or equal to 6 weeks
• Bilirubin less than or equal to 3x upper limit of normal
• AST less than or equal to 5x upper limit of normal
• ANC\>750/microliter
• Platelets \> 50,000/microliter
• Hgb ≥ 7.0g/dl (can be transfused)
• Creatinine less than or equal to 2x upper limit of normal for age, Creatinine clearance (as estimated by Cockcroft Gault or Schwartz) greater than or equal to 60 ml/min
• Pulse oximetry of \> 90% on room air
• Off investigational therapy for 4 weeks prior to study entry

You may not qualify if:

• At time of Procurement:
• Known HIV positivity
• At time of Treatment:
• Pregnant or lactating
• Severe intercurrent infection

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Cancer Institute (NCI): collaborator
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Camurati-Engelmann Syndrome; Nasopharyngeal Carcinoma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Helen Heslop, MD

  Baylor College of Medicine/Texas Children's Hospital /Houston Methodist Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director CAGT

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 19, 2014
• Study Start: February 1, 2015
• Primary Completion: March 1, 2017
• Study Completion (Estimated): February 1, 2033
• Last Updated: January 29, 2026

Record last verified: 2026-01

Locations

US (1)