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Lmp1 and Lmp2 Specific CTLs Following Cd45 Antibody for Relapsed Ebv-Positive Hodgkin's Or Non-Hodgkin's Lymphoma (ALDI)

This study has been terminated.
(The trial was terminated in 2010 due to lack of enrollment.)
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Information provided by (Responsible Party):
Stephen Gottschalk, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00383097
First received: September 28, 2006
Last updated: May 22, 2012
Last verified: May 2012
History of Changes
  Purpose

The purpose of this study is to obtain blood (up to 90 ml or 18-teaspoonfuls on one or two occasions) to make LMP1- and LMP2-cytotoxic T-lymphocytes and grow them in the laboratory in such a way that they are able to attack LMP1- and LMP2-positive cells in the laboratory.

If we are successful in growing these cells and if we feel they would be helpful to the donor, we would then give the cells back to the donor.

This trial is for patients that have a type of lymph gland cancer called Hodgkin or non-Hodgkin lymphoma, or chronic active Epstein Barr virus (EBV) infection, which has come back or not gone away after treatment, including the best treatment we know.

This is a research study using special immune system cells called LMP1- and LMP2-specific cytotoxic T lymphocytes (LMP1- and LMP2-CTLs), a new experimental therapy. As in chronic active EBV infection, some patients with Hodgkin or non-Hodgkin lymphoma show evidence of infection with the virus that causes infectious mononucleosis (EBV) before or at the time of their diagnosis of the Lymphoma. EBV is found in the cancer cells of up to half the patients with lymphoma, suggesting that 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 destruction. We want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in the patient's blood and affect EBV-positive cells. In this present study we are trying to find out if we can improve this treatment by growing T cells that only recognize two of the proteins expressed on lymphoma cells called LMP1 and LMP2. These special T cells are called LMP1- and LMP2-specific cytotoxic CTLs.


Condition Intervention Phase
Hodgkins Lymphoma
Non-Hodgkin Lymphoma
 Genetic: LMP1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES
Genetic: LMP2-SPECIFIC CYTOTOXIC T-LYMPHOCYTES
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Administration of LMP1- and LMP2- Specific Cytotoxic T-Lymphocytes Following CD45 Antibody to Patients With Relapsed EBV-Positive Hodgkin's or Non-Hodgkin's Lymphoma or Chronic Active EBV Infection (ALDI)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Dose limiting Toxicity: Two patients in each cohort are followed [ Time Frame: 6 weeks post CTL infusion ] [ Designated as safety issue: Yes ]
  • Safety: All patients who received CD45 MAbs and LMP1- and LMP2-CTL infusions will be included in the safety analysis of this combination regimen [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Laboratory data which includes CBC, BUN, creatinine, etc. will be examined at pre-infusion, and at 1, 2, 4, 6, 8 weeks post- CTL infusion, 3-month intervals for the first year [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Frequency of T cells specific for LMP1-, LMP2-, and other EBV-antigens as well as T cell specific for CMVpp65 will be measured and summarized at pre and post-infusion time points [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Changes of T cells specific for LMP1-, LMP2-, and other EBV-antigens as well as for CMVpp65 from pre-infusion to each time point of post-infusion in the overall patient group. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Analysis of immunologic function of tetramer-positive cells in peripheral blood, and EBV-DNA in plasma will be performed at each time point of follow-up and paired comparisons of changes from baseline will be performed. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Frequency of T cells specific for adenovirus and EBV. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Analysis of anti-tumor activity; Overall response rates as well as by dose groups will be presented after the end of CTL infusion. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: September 2006
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: LMP1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES
    1 injection One of the following 4 dose levels: 2x 10^7 cells/m2, 1x 10^8 cells/m2, 3 x 10^8 cells/m2, 1 x 10^9 cells/m2
    Genetic: LMP2-SPECIFIC CYTOTOXIC T-LYMPHOCYTES
    1 injection One of the following 4 dose levels: 2x 10^7 cells/m2, 1x 10^8 cells/m2, 3 x 10^8 cells/m2, 1 x 10^9 cells/m2
  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Diagnosis of EBV-positive Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL; all histological subtypes except Burkitt's lymphoma), or EBV (associated)-T/NK-LPD, or chronic active EBV infection (CAEBV) after second or subsequent relapse including after autologous or syngeneic stem cell transplant (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated). CAEBV is defined as i) illness for greater than 3 months duration (EBV-related illness or symptoms including fever, persistent hepatitis, extensive lymphadenopathy, or hepatosplenomegaly); ii) increased amounts of EBV-DNA in peripheral blood (equal or greater than 400 genome copies per ug of DNA) or abnormal high levels of EBV antibodies (VCA IgG equal or greater than 1:5120 or EA IgG equal or greater than 1:640; and iii) no evidence of previous immunological abnormalities or other recent infection that might explain the observed condition.

Patients with life expectancy greater than 6 weeks.

Patients with a Karnofsky score (age ≥16) of greater than 50 or Lansky score (age<16) of greater than 50

No severe intercurrent infection.

HIV negative donor (if autologous donor, patient must be HIV negative)

Patient, parent/guardian able to give informed consent.

Patients with bilirubin less than3 x normal, AST less than 5 x normal, and Hgb greater than 8.0

Patients with a creatinine less than 2 x normal for age

Patients should have been off other investigational therapy including T cell therapies for one month prior to entry in this study.

Female patients with reproductive capacity must have a negative pregnancy test. Women of childbearing potential must not be pregnant and must be on effective birth control. 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 CAGT Protocol Review Committee and the FDA reviewer.

Exclusion Criteria:

  • Patient, parent/guardian unable or unwilling to give informed consent
  • Pregnant women
  • Patients with a Karnofsky score of < 50
  • Patients with a severe intercurrent infection
  • Patients with a life expectancy of <6 weeks
  • Patients with a bilirubin greater than 3x normal. AST greater than 5x normal and Hgb less than 8.0 g/dl
  • Patients with a creatinine greater than 2x normal for age
  • 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: NCT00383097

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
The Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Investigators
Study Director: MALCOLM K BRENNER, MD Center for Cell and Gene Therapy, Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Stephen Gottschalk, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00383097     History of Changes
Obsolete Identifiers: NCT00608478
Other Study ID Numbers: 19275, ALDI
Study First Received: September 28, 2006
Last Updated: May 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
CTLs
LMP1
LMP2
CYTOTOXIC T-LYMPHOCYTES
 CD45
ANTIBODY
EBV-POSITIVE HODGKIN'S
NON-HODGKIN'S 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
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013