Autologous or Donor Cytotoxic T-Lymphocytes in Treating Patients with Epstein-Barr Virus-Positive Hematologic Malignancy

Status: Active

Description

This phase I / II trial studies the side effects and best dose of cytotoxic T-lymphocytes and to see how well they work in treating patients with a hematologic cancer that is positive for Epstein-Barr virus. Vaccines made from a patient or donor's white blood cells may help the body build an effective immune response to kill cancer cells.

Eligibility Criteria

Inclusion Criteria

  • Any patient, regardless of age or sex, with EBV-positive Hodgkin’s or non-Hodgkin’s Lymphoma, or lymphoepithelioma/leiomyosarcoma regardless of the histological subtype or EBV (associated)-T/NK-lymphoproliferative disease or severe chronic EBV * In second or subsequent relapse (or first relapse or with active disease if immunosuppressive chemotherapy contraindicated or multiply relapsed patients in remission who have a high risk of relapse) OR any patient with primary disease or in first remission if immunosuppressive chemotherapy is contraindicated, e.g. patients who develop Hodgkin disease after solid organ transplantation or if the Lymphoma is a second malignancy e.g. a Richters transformation of chronic lymphocytic leukemia (CLL) (Group A) OR * In remission or with minimal residual disease status after autologous or syngeneic stem cell transplantation (SCT) (Group B) OR * In remission or with detectable disease after allogeneic SCT (Group C)
  • Patients with life expectancy >= 6 weeks
  • Tumor tissue EBV positive
  • Patients with a Karnofsky/Lansky score of >= 50
  • Donor human immunodeficiency virus (HIV) negative (if autologous product – patient must be HIV negative)
  • If post allogeneic SCT must not have less than 50% donor chimerism in either peripheral blood or bone marrow
  • Bilirubin =< 3 x normal
  • Aspartate aminotransferase (AST) =< 5 x normal
  • Hemoglobin (Hgb) > 8.0
  • Patients with a creatinine =< 2 x normal for age
  • Patients should have been off other investigational therapy for one month prior to entry in this study
  • Patient, parent/guardian able to give informed consent

Exclusion Criteria

  • Patients with severe intercurrent infection
  • Donors who are HIV positive (Patients who are HIV positive - if autologous product)
  • Patients with graft-versus-host disease (GVHD) > grade II
  • 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 Center for Cell and Gene Therapy (CCGT) Protocol Review Committee and the Food and Drug Administration (FDA) reviewer

Locations & Contacts

District of Columbia

Washington
Children's National Medical Center
Status: Active
Contact: Catherine Mary Bollard
Phone: 202-884-2549
Email: cbollard@cnmc.org

Maryland

Bethesda
National Institute of Allergy and Infectious Diseases (NIAID)
Status: Active
Contact: Jeffrey I. Cohen
Phone: 301-496-5265
Email: jcohen@niaid.nih.gov

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Helen Elisabeth Heslop
Phone: 832-824-4662
Email: burton@bcm.edu
Texas Children's Hospital
Status: Active
Contact: Helen Elisabeth Heslop
Phone: 832-824-4662
Email: burton@bcm.edu
The Methodist Hospital System
Status: Active
Contact: Helen Elisabeth Heslop
Phone: 832-824-4662
Email: burton@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety of 2 intravenous injections of autologous or allogeneic LMP-specific cytotoxic T-lymphocytes (CTL) in patients with Epstein-Barr virus (EBV)-associated Hodgkin’s disease or lymphoma/lymphoproliferation/severe chronic EBV.

II. To determine the survival and the immune function of LMP-specific cytotoxic T-lymphocyte lines.

III. To assess the anti-viral and anti-tumor effects of LMP-specific CTL.

IV. To obtain preliminary information on the safety and response to an extended dosage regimen.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients receive autologous or allogeneic LMP-specific cytotoxic T-lymphocytes intravenously (IV) over 1-10 minutes on days 0 and 14. Treatment may repeat monthly for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 weeks for 8 weeks; at 3, 6, 9, and 12 months; and then yearly for 5 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Helen Elisabeth Heslop

Trial IDs

Primary ID ALCI
Secondary IDs NCI-2012-00653, H-9936, NCT00671164, NCT00070226, 9936-ALCI
Clinicaltrials.gov ID NCT00062868