Safety Study of Injections of Autologous/Allogeneic TGFbeta-resistant LMP2A-specific Cytotoxic T-lymphocytes (CTL) - Full Text View

Sponsor:	Baylor College of Medicine
Collaborators:	Texas Children's Hospital The Methodist Hospital System Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00368082

Purpose

In this study the investigators will generate autologous (or syngeneic) or allogeneic LMP-specific cytotoxic T-cells and genetically modify them using a retroviral vector expressing a dominant negative TGFb receptor II (DNRII) to render them resistant to the immunosuppressive effects of TGFb. The investigators will then adoptively transfer these TGFb resistant LMP-CTL to patients with relapsed EBV-positive Hodgkin's or non-Hodgkins Lymphoma or Lymphoepithelioma. The investigators will generate LMP-specific CTL using the same methodology as in our current clinical study. The in vitro expanded CTL will then be transduced with a retrovirus vector expressing the dominant TGFb receptor II to improve their activity and persistence in the presence of TGFb secreted by the tumor cells in vivo.

The main objectives of the study are: 1.To determine the safety of 2 intravenous injections of autologous or allogeneic TGFbeta-resistant LMP2A-specific cytotoxic T-lymphocytes (CTL) in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. 2.To determine the survival and the immune function of TGFbeta-resistant LMP2A-specific cytotoxic T-lymphocyte lines. 3.To assess the anti-viral and anti-tumor effects of TGFbeta-resistant LMP2A-specific CTL. 4.To obtain preliminary information on the safety and response to an extended dosage regimen.

Condition	Intervention	Phase
RELAPSED EBV-POSITIVE LYMPHOMA	Genetic: TGF-b RESISTANT LMP2A-SPECIFIC CYTOTOXIC T-LYMPHOCYTES	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	ADMINISTRATION OF TGF-b RESISTANT LMP2A-SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO PATIENTS WITH RELAPSED EBV-POSITIVE LYMPHOMA

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

Safety and MTD of 2 IV injections of autologous/syngeneic or allogeneic TGFb resistant LMP2A-specific cytotoxic T-lymphocytes. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
Survival and immune function of TGFbeta-resistant LMP-specific cytotoxic T-lymphocytes [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
determine anti-viral and anti-tumor effects of TGFbeta resistant LMP-specific CTL [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	April 2006
Estimated Study Completion Date:	December 2025
Estimated Primary Completion Date:	December 2025 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A Patients in second or subsequent relapse including after autologous or syngeneic stem cell transplant	Genetic: TGF-b RESISTANT LMP2A-SPECIFIC CYTOTOXIC T-LYMPHOCYTES 2x107 cells/m2 6x107 cells/m2 1.5x 108 cells/m2 Each patient will receive 2 injections, 14 days apart
Experimental: B patients with detectable/relapsed EBV+ disease after allogeneic SCT confirmed by biopsy	Genetic: TGF-b RESISTANT LMP2A-SPECIFIC CYTOTOXIC T-LYMPHOCYTES 2x107 cells/m2 6x107 cells/m2 1.5x 108 cells/m2 Each patient will receive 2 injections, 14 days apart

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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 a relapse biopsy sample

Primary refractory lymphoma or in second or subsequent relapse including after autologous or syngeneic stem cell transplant (Group A) OR

In patients with detectable/relapsed EBV+ disease after allogeneic SCT confirmed by biopsy. (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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00368082

Contacts

Contact: Catherine M Bollard, MD	832-824-4781 ext 4-4781	cbollard@bcm.tmc.edu
Contact: Helen E Heslop, MD	832-824-4662 ext 4-4662	hheslop@bcm.tmc.edu

Locations

United States, Texas
Center for Cell and Gene Therapy	Recruiting
Houston, Texas, United States, 77030
Contact: Catherine M Bollard, MD 832-824-4781 ext 4-4781 cmbollar@txccc.org
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Catherine M Bollard, MD
Sub-Investigator: Bambi J Grilley
Sub-Investigator: Robert A Krance, MD
Sub-Investigator: Malcolm Brenner, MD
Sub-Investigator: Helen Heslop, MD
Sub-Investigator: Cliona M Rooney, MD
Sub-Investigator: Adrian Gee, MD
Sub-Investigator: Stephen Gottschalk, MD
Sub-Investigator: Carlos Ramos, MD
Sub-Investigator: Gianpietro Dotti, MD
Sub-Investigator: Hao Liu
Texas Childrens Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Catherine M Bollard, MD 832-824-4781 cmbollar@txccc.org
Sub-Investigator: Andrea M Sheehan, MD

Sponsors and Collaborators

Baylor College of Medicine

Texas Children's Hospital

The Methodist Hospital System

Center for Cell and Gene Therapy, Baylor College of Medicine

Investigators

Study Director:

Malcolm K Brenner, MD

Center for Cell and Gene Therapy, Baylor College of Medicine

More Information

No publications provided

Responsible Party:	Helen Heslop, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00368082 History of Changes
Obsolete Identifiers:	NCT00675571
Other Study ID Numbers:	17946-TGFBeta, TGF-beta
Study First Received:	August 22, 2006
Last Updated:	August 12, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

EBV-POSITIVE LYMPHOMA
Hodgkin´s Disease (HD)
Non-Hodgkin's lymphoma (NHL)

Additional relevant MeSH terms:

Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on February 09, 2012