Autologous/Allogeneic TGFbeta-resistant LMP-specific CTL, Lymphoma (TGF-beta)

NCT00368082 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 17946-TGFBetaTGF-beta
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

Patients have a type of lymph gland cancer called HD, NHL or lymphoepithelioma (these 3 diseases will be referred to as "Lymphoma"). The lymphoma has come back or has not gone away after treatment. This is a research study using special immune system cells called TGFb-resistant LMP-specific cytotoxic T lymphocytes (DNR-CTL), a new experimental therapy. Some patients with Lymphoma show signs of infection with the Epstein Barr virus (EBV) before or at the time of their Lymphoma diagnosis. EBV is found in the cancer cells of up to 1/2 the patients with Lymphoma, suggesting it may play a role in causing Lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed by releasing a substance called Transforming Growth Factor-beta (TGFb). The investigators want to see if special white blood cells (called T cells) that have been given a gene that they hope will let them survive against TGFb and that have been trained to kill EBV infected cells can also survive in the blood and kill the tumor. Investigators have used this sort of therapy with specially trained T cells 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 they were able to successfully prevent and treat post transplant lymphoma. However when they used a similar approach in HD some patients had a partial response to this therapy, but no patients had a complete response. In a follow-up study they tried to find out if they could improve this treatment by growing T cells that recognize 2 of the proteins expressed on Lymphoma cells called LMP-1 and LMP2a. These special T cells were called LMP-specific cytotoxic T-lymphocytes (CTLs). Although some patients had tumor responses, CTL therapy alone did not cure those who had a lot of disease. Investigators think that a reason for this is that the tumor cells are releasing TGFb. For this reason, they want to find out if they can make the CTL resistant to TGFb by putting in a new gene called TGFb resistance gene. Investigators hope that this will improve this treatment for relapsed lymphoma. These TGFb-resistant LMP-specific CTLs are an investigational product not approved by FDA. The purpose of this study is to find the largest safe dose of TGFb resistant LMP-specific CTLs, to learn what the side effects are and to see whether this therapy might help patients with Lymphoma.

Conditions

Lymphoma; Hodgkin's Disease; Relapse; Lymphoma, Non-Hodgkin

Keywords

EBV-Positive Lymphoma; Hodgkin´s Disease (HD); Non-Hodgkin's lymphoma (NHL); relapsed Hodgkin's disease; relapsed non-Hodgkin's disease; lymphoma; TGFbeta resistant LMP-specific CTLs; cytotoxic T cells

Outcome Measures

Primary Outcomes (1)

• Safety and MTD of 2 IV injections of autologous/syngeneic or allogeneic TGFb resistant LMP-specific cytotoxic T-lymphocytes.

  Number of patients with Dose-Limiting Toxicity (DLT).

  6 weeks

Secondary Outcomes (2)

• Survival and immune function of TGFbeta-resistant LMP-specific cytotoxic T-lymphocytes.

  15 years

• Determine anti-viral and anti-tumor effects of TGFbeta resistant LMP-specific CTL.

  15 years

Study Arms (1)

TGFbeta resistant LMP-specific CTLs

EXPERIMENTAL

CTLs be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. If patients with active disease have stable disease or a partial response at their 6 week or subsequent evaluations they will be eligible to receive up to 6 additional doses of CTLs at 1-2 monthly intervals-each of which will consist of the same cell number as their second injection.

Biological: TGFbeta resistant LMP-specific CTLs

Interventions

TGFbeta resistant LMP-specific CTLs BIOLOGICAL

Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Group One: Day 0 2 x 10\^7 cells/m2 Day 14 2 x 10\^7 cells/m2 Group Two: Day 0 6 x 10\^7 cells/m2 Day 14 6 x 10\^7 cells/m2 Group Three: Day 0 1.5 x 10\^8 cells/m2 Day 14 1.5 x 10\^8 cells/m2

Also known as: TGF-b Resistant LMP2A-Specific Cytotoxic T-Lymphocytes

TGFbeta resistant LMP-specific CTLs

Eligibility Criteria

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

You may qualify if:

• Any patient, regardless of age or sex, with EBV-positive lymphoma, or lymphoepithelioma regardless of the histological subtype or EBV (associated)-T/NK-LPD all confirmed on any tissue sample.
• Primary refractory lymphoma or in second or subsequent relapse including after autologous or syngeneic stem cell transplant OR patients at a high risk for relapse defined as: (i) patients with primary refractory lymphoma or multiply relapsed lymphoma who are in remission but not eligible for autologous SCT or (ii) patients with relapsed lymphoma after autologous SCT who are in remission but not eligible for allogeneic SCT (Group A)
• Any patient who has received an allogeneic SCT for EBV Lymphoma or EBV (associated)-T/NK-LPD or Lymphoepithelioma (Group B)
• Patients with life expectancy 6 weeks or greater from the time of CTL infusion.
• Patients with a Karnofsky score of 50 or greater.
• If post allogeneic SCT must not have less than 50% donor chimerism in either peripheral blood or bone marrow
• Patients with bilirubin 3x normal or less, AST 5x normal or less, and Hgb greater than 8.0
• Patients with a creatinine 2x normal for age or less
• Patients with O2 saturations greater than 93% on room air (measured by pulse oximetry)
• Patient, parent/guardian able to give informed consent.
• Patients should have been off other investigational therapy for one month prior to entry in this study.

You may not qualify if:

• Patients with a severe intercurrent infection.
• Patients with evidence of GVHD greater than Grade II at time of enrollment.
• HIV positive at time of procurement cells for CTL generation
• 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 Childrens Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Bollard CM, Tripic T, Cruz CR, Dotti G, Gottschalk S, Torrano V, Dakhova O, Carrum G, Ramos CA, Liu H, Wu MF, Marcogliese AN, Barese C, Zu Y, Lee DY, O'Connor O, Gee AP, Brenner MK, Heslop HE, Rooney CM. Tumor-Specific T-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients With Relapsed Hodgkin Lymphoma. J Clin Oncol. 2018 Apr 10;36(11):1128-1139. doi: 10.1200/JCO.2017.74.3179. Epub 2018 Jan 9.

  PMID: 29315015 DERIVED

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Recurrence; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Helen E Heslop, 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: Professor

Study Record Dates

• First Submitted: August 22, 2006
• First Posted: August 24, 2006
• Study Start: April 1, 2006
• Primary Completion: September 1, 2013
• Study Completion (Estimated): July 1, 2031
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (2)