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

NCT00383097 | Terminated Phase 1 DMC

• 2 other identifiers: 19275ALDI
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hodgkins Lymphoma; Non-Hodgkin Lymphoma

Keywords

CTLs; LMP1; LMP2; CYTOTOXIC T-LYMPHOCYTES; CD45; ANTIBODY; EBV-POSITIVE HODGKIN'S; NON-HODGKIN'S LYMPHOMA

Outcome Measures

Primary Outcomes (2)

• Dose limiting Toxicity: Two patients in each cohort are followed

  6 weeks post CTL infusion

• Safety: All patients who received CD45 MAbs and LMP1- and LMP2-CTL infusions will be included in the safety analysis of this combination regimen

  1 year

Secondary Outcomes (6)

• 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

  1 year

• 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

  1 year

• 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.

  1 year

• 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.

  1 year

• Frequency of T cells specific for adenovirus and EBV.

  1 year

Interventions

LMP1 SPECIFIC CYTOTOXIC T-LYMPHOCYTES GENETIC

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

LMP2-SPECIFIC CYTOTOXIC T-LYMPHOCYTES GENETIC

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

Eligibility Criteria

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

You may qualify if:

• 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.

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 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: 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

Hodgkin Disease; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

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

Study Officials

• MALCOLM K BRENNER, MD

  Center for Cell and Gene Therapy, Baylor College of Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 28, 2006
• First Posted: October 2, 2006
• Study Start: September 1, 2006
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: May 24, 2012

Record last verified: 2012-05

Locations

US (2)