LMP2a-Specific Cytotoxic T-Lymphocytes, Lymphoma (ACDAL)

NCT00082225 | Terminated Phase 1 DMC

• 2 other identifiers: 14424-ACDALACDAL
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

Patients have a type of cancer called Hodgkin's lymphoma or non-Hodgkin's lymphoma, which has come back or not gone away or is at high risk for coming back after treatment, including the best treatment investigators know for this disease. Investigators are asking the patient to volunteer to be in a research study using a new experimental therapy consisting of special immune system cells called LMP2 specific cytotoxic T lymphocytes in combination with a special protein called a monoclonal antibody. Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (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. Investigators want to see if special white blood cells, called T cells, that have been trained to kill EBV infected cells can survive in the blood and affect the tumor. The investigators 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. They grew T cells in the laboratory that recognized all 9 proteins and were able to prevent and treat post transplant lymphoma. However in Hodgkin disease and non-Hodgkin Lymphoma the tumor cells only express 2 EBV proteins. In a previous study investigators made T cells that recognized all 9 proteins and gave them to patients with Hodgkin disease. Some patients had a partial response to this therapy but no patients had a complete response. Investigators think one reason may be that many of the T cells reacted with proteins that were not on the tumor cells. They are now trying to find out if they can improve this treatment by growing T cells that only recognize one of the proteins expressed on Lymphoma cells called LMP-2. These special T cells are called LMP-2 specific cytotoxic T-lymphocytes (CTLs). In this study investigators also are trying to see if they can improve these results by treating patients first with a special protein called an antibody and then giving the EBV specific T cells. The reason for doing this is that EBV specific T cells have worked very well in bone marrow transplant patients to prevent and treat EBV cancers. These patients have very few of their own immune cells when they are given the trained T cells and therefore there is a lot of space for the trained cells to grow. Investigators hope that they can improve the effect of the trained T cells in Hodgkin disease and non-Hodgkin Lymphoma patients by first temporarily removing the patient's own T cells before giving the trained cells.

Conditions

Lymphoma

Keywords

Hodgkins; Non-Hodgkins; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Adverse event data per patient

  To determine the safety of autologous/syngeneic or allogeneic LMP-2 specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (Mab) in patients with EBV positive Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL).

  6 weeks

Secondary Outcomes (1)

• Survival of CTLs

  up to 8 weeks

Study Arms (1)

EBV specific T cells

EXPERIMENTAL

Patients receiving CTLs as therapy for relapsed Lymphoma or who are at high risk for relapse or patients receiving CTLs as adjunctive therapy following autologous or syngeneic transplant. A fixed dose of CD45 MAb (400ug/kg over 4 hours daily times 4 given over 2 daily IV infusions) will be used.

Biological: CD45 antibodies; Biological: EBV specific T cells

Interventions

CD45 antibodies BIOLOGICAL

The antibody solution is administered by a syringe pump in incremental doses, 0.2-0.8 mg in the first hour and up to 10 mg/hr thereafter, for a maximum infusion time of 8 hrs.

EBV specific T cells

EBV specific T cells BIOLOGICAL

The following dose levels will be evaluated: Each patient will receive 1 injection, according to the following dosing schedules: 2 x 10e7 cells/m2 5 x 10e7 cells/m2 1 x 10e8 cells/m2

EBV specific T cells

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 Hodgkin's or non-Hodgkin lymphoma, regardless of the histological subtype or EBV-associated T/NK cell Lymphoproliferative disease. This includes patients in second or subsequent relapse including post autologous or syngeneic stem cell transplant (or with active disease or in first relapse if immunosuppressive chemotherapy contraindicated or if the patient has relapsed multiple times and is currently in remission but has a high risk of relapse). (group A) OR Patients who have relapsed after allogeneic stem cell transplant for Hodgkin's Lymphoma or non-Hodgkin's Lymphoma (Group B)
• Life expectancy of greater than or equal to 6 weeks
• No severe intercurrent infection
• Patient, parent/guardian able to give informed consent
• Donor must be HIV negative (if autologous product used - patient must be HIV negative)
• Bilirubin less than or equal to 3x normal
• AST less than or equal to 5x normal
• Hgb higher than 8.0 g/L
• Creatinine less than or equal to 2x normal for age
• Patients should have been off other investigational therapy including T cells therapies for one month prior to entry in this study
• Karnofsky score of over or equal to 50
• No evidence of GVHD \>Grade II at time of enrollment
• Female patients with reproductive capacity must have a negative pregnancy test

You may not qualify if:

• 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 of more than 3x normal. AST of more than 5x normal
• Patients with a creatinine of more than 2x normal for age
• GVHD greater than Grade II at time of enrollment
• 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.

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)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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: May 3, 2004
• First Posted: May 5, 2004
• Study Start: October 1, 2003
• Primary Completion: February 1, 2006
• Study Completion: January 1, 2008
• Last Updated: February 7, 2017

Record last verified: 2017-02

Locations

US (2)