LMP1- and LMP2-Specific CTLs to Patients With EBV-Positive NPC (NATELLA)

NCT00516087 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 21000-NATELLANATELLA
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

Patients have a type of cancer called nasopharyngeal carcinoma (NPC) which has either come back, not gone away or is at high risk for coming back after the best treatment we know for this disease. We are inviting patients to participate in a research study using a new experimental therapy consisting of special immune system cells called LMP1- and LMP2-specific cytotoxic T lymphocytes (LMP1- and LMP2-CTLs). Some patients with nasopharyngeal carcinoma 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 blood and affect the tumor. We have used this sort of therapy to treat a different type of cancer that occurs after bone marrow and solid organ transplant called post-transplant lymphoma. In this type of cancer the tumor cells have 9 proteins made by EBV on their surface. We grew T cells in the laboratory that recognized all 9 proteins and were able to prevent and treat post-transplant lymphoma. However nasopharyngeal carcinoma tumor cells only express 2 EBV proteins (LMP1 and LMP2) on their surfaces. In a previous study we made T cells that recognized all 9 proteins and gave them to patients with NPC. While some patients had a response, only a few patients had their cancer completely go away. We are now trying to find out if we can improve this treatment by growing and giving T cells where more of the cells will recognize two of the proteins expressed on NPC cells called LMP1 and LMP2. These special T cells are called LMP1- and LMP2-CTLs. These LMP1- and LMP2-CTLs are an investigational product not approved by the Food and Drug Administration.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• adverse events are being measured/assessed for the safety of autologous LMP1- and LMP2- specific cytotoxic T-lymphocytes (CTL) in patients with EBV-positive nasopharyngeal carcinoma (NPC).

  12 months

Secondary Outcomes (1)

• Adverse events will be measured/obtained for information on the expansion, persistence and anti-tumor effects of autologous LMP1- and LMP2 specific CTL in patients with EBV-positive NPC.

  12 months

Study Arms (1)

Patients

EXPERIMENTAL

Patients with NPC in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive disease) in whom the EBV genome or antigens have been demonstrated in tissue biopsies.

Biological: Genetically modified CTLs

Interventions

Genetically modified CTLs BIOLOGICAL

LMP1- and LMP2-specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. Three different dosing schedules will be evaluated. Each patient will receive two injections, 14 days apart, according to the following dosing schedules: Group One Day 0 2x10\^7 cells/m2 Day 14 2x10\^7 cells/m2 Group Two Day 0 2x10\^7 cells/m2 Day 14 1x10\^8 cells/m2 Group Three Day 0 1x10\^8 cells/m2 Day 14 2x10\^8 cells/m2

Patients

Eligibility Criteria

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

You may qualify if:

• All patients with NPC in first or subsequent relapse or with primary refractory disease or high risk (T3 or T4, or node positive disease) in whom the EBV genome or antigens have been demonstrated in tissue biopsies will be eligible for this trial.
• Any patient with EBV positive NPC, in relapse or with primary resistant disease
• Patients with a life expectancy 6 weeks or greater
• Patients with bilirubin less than 2x normal, SGOT less than 3x normal, and Hgb more than 8.0.
• Patients with a Karnofsky score (age greater than/=16) of or Lansky score (age less than 16) of greater than/= 50
• Patients with a creatinine 2x normal for age or less
• Patients should have been off other investigational therapy for one month prior to entry in this study
• Patient, parent/guardian able to give informed consent

You may not qualify if:

• Severe intercurrent infection
• Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom.

Sponsors & Collaborators

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

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Stephen Gottschalk, MD

  Baylor College of Medicine

  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: Associate Professor

Study Record Dates

• First Submitted: August 10, 2007
• First Posted: August 14, 2007
• Study Start: August 1, 2007
• Primary Completion: December 1, 2012
• Study Completion: July 1, 2013
• Last Updated: February 7, 2017

Record last verified: 2017-02

Locations

US (2)