LMP-specific T-cells for Patients With Relapsed EBV-positive Lymphoma - 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:	NCT00062868

Purpose

To determine the safety of 2 intravenous injections of autologous or allogeneic LMP-specific cytotoxic T-lymphocytes (CTL) in patients with EBV-associated Hodgkin's Disease or lymphoma/lymphoproliferation/severe chronic EBV.

To determine the survival and the immune function of LMP-specific cytotoxic T-lymphocyte lines.

To assess the anti-viral and anti-tumor effects of LMP-specific CTLs.

To obtain preliminary information on the safety and response to an extended dosage regimen.

Condition	Intervention	Phase
Hodgkin Disease Non Hodgkin Lymphoma	Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 1) Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 2) Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 3)	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 LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Hodgkin's and Non-Hodgkin Lymphoma.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Hodgkin Disease Lymphoma

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

Safety of 2 intravenous injections of autologous or allogeneic LMP-specific cytotoxic T-lymphocytes (CTL) in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
To determine the survival and the immune function of LMP-specific cytotoxic T-lymphocyte lines. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
To assess the anti-viral and anti-tumor effects of LMP-specific CTL. [ Time Frame: 5 yearas ] [ Designated as safety issue: No ]
To obtain preliminary information on the safety and response to an extended dosage regimen [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	108
Study Start Date:	April 2007
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A Patients receiving CTLs as therapy for relapsed Lymphoma/Lymphoepithelioma or who are at high risk for relapse	Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 1) Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Day 0 2 x 10e7 cells/m2 Day 14 2 x 10e7 cells/m2 Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 2) Group Two: Day 0 2 x 107 cells/m2 Day 14 1 x 108 cells/m2 2 injections, 14 days apart Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 3) Day 0 1 x 108 cells/m2 Day 14 2 x 108 cells/m2 2 injections, 14 days apart
Experimental: B Patients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant	Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 1) Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Day 0 2 x 10e7 cells/m2 Day 14 2 x 10e7 cells/m2 Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 2) Group Two: Day 0 2 x 107 cells/m2 Day 14 1 x 108 cells/m2 2 injections, 14 days apart Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 3) Day 0 1 x 108 cells/m2 Day 14 2 x 108 cells/m2 2 injections, 14 days apart
Experimental: C Patients receiving CTLs following allogeneic stem cell transplant	Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 1) Each patient will receive 2 injections, 14 days apart, according to the following dosing schedules: Day 0 2 x 10e7 cells/m2 Day 14 2 x 10e7 cells/m2 Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 2) Group Two: Day 0 2 x 107 cells/m2 Day 14 1 x 108 cells/m2 2 injections, 14 days apart Biological: Injection of LMP Specific Cytotoxic T-Lymphocytes (group 3) Day 0 1 x 108 cells/m2 Day 14 2 x 108 cells/m2 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 Hodgkin's or non-Hodgkin's Lymphoma, or lymphoepithelioma or leiomyosarcoma regardless of the histological subtype or EBV (associated)-T/NK-lymphoproliferative disease or Severe Chronic EBV*
- In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients currently in remission who have a high risk of relapse) OR with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of CLL.(Group A)
OR
- In remission or with minimal residual disease status after autologous or syngeneic SCT for Hodgkin's or non-Hodgkin's Lymphoma/Lymphoepithelioma/SCAEBV. (Group B)
OR
- Patients after allogeneic SCT for Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma/Lymphoepithelioma/SCAEBV. (Group C)
Patients with life expectancy 6 weeks or greater
Tumor tissue EBV positive
Patients with a Karnofsky/Lansky score of 50 or greater
Donor HIV negative (if autologous product - patient must be HIV negative)
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 or less for age
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
- SCAEBV is defined as patients with high EBV viral load in plasma or PBMC (>4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV

Exclusion Criteria:

Patients with a severe intercurrent infection
Donors who are HIV positive or Patients who are HIV positive if autologous product to be used
Patients with greater than Grade II GVHD
Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom

Note: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA reviewer.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00062868

Contacts

Contact: Catherine M Bollard, MD	832-824-4781	cmbollar@txccc.org
Contact: Helen Heslop, MD	832-824-4662	hheslop@bcm.edu

Locations

United States, Texas
Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Catherine M Bollard, MD 832-824-4781 cmbollar@txccc.org
Contact: Helen E Heslop, MD 832-824-4662 hheslop@bcm.edu
Principal Investigator: Helen E Heslop, MD
Principal Investigator: Catherine M Bollard, MD
The Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Helen E Heslop, MD 832-824-4662 hheslop@bcm.edu
Contact: Catherine M Bollard, MD 832-824-4781 cmbollar@txccc.org
Principal Investigator: Helen E Heslop, MD
Principal Investigator: Catherine Bollard, MD
Sub-Investigator: Kelty Baker, MD
Sub-Investigator: Alex Preti, MD
Sub-Investigator: George Carrum, MD
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Catherine M Bollard, MD 832-824-4781 cbollard@bcm.tmc.edu
Principal Investigator: Catherine M Bollard, 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

Principal Investigator:	Steve Gottschalk, MD	Center for Cell and Gene Therapy, Baylor College of Medicine
Principal Investigator:	Helen E Heslop, MD	Center for Cell and Gene Therapy, Baylor College of Medicine
Principal Investigator:	Catherine Bollard, MD	Center for Cell and Gene Therapy, Baylor College of Medicine
Principal Investigator:	Cliona M Rooney, PhD	Center for Cell and Gene Therapy, Baylor College of Medicine

More Information

No publications provided by Baylor College of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. Epub 2011 Mar 31.

Fox CP, Haigh TA, Taylor GS, Long HM, Lee SP, Shannon-Lowe C, O'Connor S, Bollard CM, Iqbal J, Chan WC, Rickinson AB, Bell AI, Rowe M. A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK- and T-cell lymphoproliferative disease encodes a target for cellular immunotherapy. Blood. 2010 Nov 11;116(19):3695-704. Epub 2010 Jul 29.

Bollard CM, Gottschalk S, Leen AM, Weiss H, Straathof KC, Carrum G, Khalil M, Wu MF, Huls MH, Chang CC, Gresik MV, Gee AP, Brenner MK, Rooney CM, Heslop HE. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood. 2007 Oct 15;110(8):2838-45. Epub 2007 Jul 3.

Responsible Party:	Helen Heslop, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00062868 History of Changes
Obsolete Identifiers:	NCT00671164
Other Study ID Numbers:	9936-ALCI
Study First Received:	June 17, 2003
Last Updated:	August 12, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

Lymphoma

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms

Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on February 12, 2012