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T-Lymphocytes in Treating Patients With Epstein-Barr Virus-Positive Lymphoma, Lymphoepithelioma, or Severe Chronic Epstein-Barr Virus Infection Syndrome
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: May 2, 2008   Last Updated: June 9, 2009   History of Changes
Sponsored by: Baylor College of Medicine
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00671164
  Purpose

RATIONALE: Treating a person's or donor's T-lymphocytes in the laboratory and reinfusing them may cause a stronger immune response to kill Epstein-Barr virus-associated cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of T-lymphocytes in treating patients with Epstein-Barr virus-positive lymphoma, lymphoepithelioma, or severe chronic Epstein-Barr virus infection syndrome.


Condition Intervention Phase
Head and Neck Cancer
Lymphoma
Lymphoproliferative Disorder
Precancerous/Nonmalignant Condition
Small Intestine Cancer
Biological: allogeneic LMP1-/LMP2- specific cytotoxic T-lymphocytes
Biological: autologous LMP1-/LMP2- specific cytotoxic T-lymphocytes
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: Administration of LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Safety and toxicity [ Designated as safety issue: Yes ]
  • Survival of LMP-specific cytotoxic T-lymphocytes [ Designated as safety issue: No ]
  • Immunological efficacy and antitumor activity [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: April 2007
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To determine the safety of autologous or allogeneic LMP-specific cytotoxic T-lymphocytes (CTL) in patients with Epstein-Barr virus (EBV)-positive lymphoma, lymphoepithelioma, or severe chronic active EBV infection syndrome.
  • To determine the survival and immune function of LMP-specific CTL.
  • To assess the antiviral and antitumor effects of LMP-specific CTL.
  • To obtain preliminary information on the safety of and response to an extended dosage regimen.

OUTLINE: This is a dose-escalation study. Patients are stratified according disease status (relapsed lymphoma/lymphoepithelioma or at high risk for relapse vs in remission or has minimal residual disease after autologous or syngeneic stem cell transplantation vs in remission or has detectable disease after allogeneic stem cell transplantation).

Peripheral blood mononuclear cells (PBMC) are collected from the patient or a donor for generation of LMP-specific cytotoxic T-lymphocytes (CTL). PBMC are stimulated with antigen-presenting cells (APC) expressing LMP1/2 antigen and expanded with aldesleukin.

Patients receive autologous or allogeneic LMP-specific CTLs IV over 1-10 minutes on days 0 and 14. Patients are evaluated at 8 weeks. Patients with stable disease or a partial response may receive 6 additional doses of CTLs once a month.

After completion of study treatment, patients are followed at 3, 6, 9, and 12 months and then annually for 5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of any of the following:

    • Epstein-Barr virus (EBV)-positive Hodgkin or non-Hodgkin lymphoma
    • Lymphoepithelioma of any histological subtype
    • EBV (associated)-T/NK-lymphoproliferative disease
    • Severe chronic active EBV infection syndrome (SCAEBV)

      • SCAEBV is defined as a high EBV viral load in plasma or peripheral blood mononuclear cells (PBMC) (> 4,000 genomes/ug PBMC DNA) and/or biopsy tissue positive for EBV
  • Meets 1 of the following criteria:

    • In second or subsequent relapse (or in first relapse or has active disease, if immunosuppressive chemotherapy contraindicated, or disease relapsed multiple times and is currently in remission but has a high risk of relapse) OR has primary disease or in first remission, if immunosuppressive chemotherapy is contraindicated, (e.g., developed Hodgkin lymphoma after solid organ transplantation) or if the lymphoma is a second malignancy (e.g., Richter transformation of chronic lymphocytic leukemia)
    • In remission or has minimal residual disease after autologous or syngeneic stem cell transplantation (SCT)
    • In remission or has detectable disease after allogeneic SCT
  • At least 50% donor chimerism in either peripheral blood or bone marrow (for patients who have undergone prior allogeneic SCT)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) OR Lansky PS 50-100%
  • Life expectancy ≥ 6 weeks
  • Hemoglobin > 8.0 g/dL
  • Prothrombin time normal
  • Bilirubin ≤ 3 times normal
  • AST ≤ 5 times normal
  • Creatinine ≤ 2 times normal for age
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No concurrent severe infection
  • No grade III-IV graft-vs-host disease

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 1 month since prior investigational therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00671164

Locations
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor     713-798-1297        
Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Vicky Torrano     832-824-7821        
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030-2399
Contact: Vicky Torrano     832-824-7821        
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Catherine Bollard Baylor College of Medicine
Principal Investigator: Helen E. Heslop, MD Baylor College of Medicine
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):
Study ID Numbers: CDR0000595213, BCM-H-9936-ALCI
Study First Received: May 2, 2008
Last Updated: June 9, 2009
ClinicalTrials.gov Identifier: NCT00671164     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
Epstein-Barr virus infection
post-transplant lymphoproliferative disorder
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
stage I adult Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage II childhood Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
adult grade III lymphomatoid granulomatosis
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
recurrent adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
recurrent adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma

Study placed in the following topic categories:
Precancerous Conditions
Hodgkin Lymphoma, Childhood
Gastrointestinal Diseases
Central Nervous System Lymphoma, Primary
Ileal Diseases
Epstein Barr Virus, Chronic
Lymphoma, Large-cell, Immunoblastic
Lymphoma, Small Cleaved-cell, Diffuse
Duodenal Neoplasms
Ileal Neoplasms
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-Cell, Anaplastic
Epstein-Barr Virus Infections
Lymphoma, Large-cell
Hodgkin Disease
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Lymphomatoid Granulomatosis
Lymphoma, Large B-Cell, Diffuse
Digestive System Neoplasms
Immunoproliferative Disorders
Hodgkin Lymphoma, Adult
Immunoblastic Lymphadenopathy
Hodgkin's Disease
Small Non-cleaved Cell Lymphoma
Intestinal Diseases
Recurrence
Intestinal Neoplasms

Additional relevant MeSH terms:
Precancerous Conditions
Gastrointestinal Diseases
Tumor Virus Infections
Ileal Diseases
Neoplasms, Experimental
Duodenal Neoplasms
Neoplasms by Site
Ileal Neoplasms
Jejunal Diseases
Lymphoma, Large-Cell, Immunoblastic
Epstein-Barr Virus Infections
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Neoplasms by Histologic Type
Immunoproliferative Disorders
Digestive System Neoplasms
Immune System Diseases
Intestinal Diseases
Intestinal Neoplasms
Herpesviridae Infections
Virus Diseases
Lymphatic Diseases
Neoplasms
Digestive System Diseases
Head and Neck Neoplasms
Gastrointestinal Neoplasms
DNA Virus Infections
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 02, 2009