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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.
Study NCT00671164   Information provided by National Cancer Institute (NCI)
First Received: May 2, 2008   Last Updated: June 9, 2009   History of Changes

May 2, 2008
June 9, 2009
April 2007
May 2015   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT00671164 on ClinicalTrials.gov Archive Site
 
 
 
T-Lymphocytes in Treating Patients With Epstein-Barr Virus-Positive Lymphoma, Lymphoepithelioma, or Severe Chronic Epstein-Barr Virus Infection Syndrome
Administration of LMP-Specific Cytotoxic T-Lymphocytes to Patients With Relapsed EBV-Positive Lymphoma

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.

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.

Phase I
Interventional
Treatment
  • 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
 
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.

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Recruiting
36
 
May 2015   (final data collection date for primary outcome measure)

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
Both
 
No
 
United States
 
NCT00671164
 
CDR0000595213, BCM-H-9936-ALCI
Baylor College of Medicine
 
Principal Investigator: Catherine Bollard Baylor College of Medicine
Principal Investigator: Helen E. Heslop, MD Baylor College of Medicine
National Cancer Institute (NCI)
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP