Modified T-Cells in Treating Patients With Epstein-Barr Virus Positive Lymphoma.

Status: Active

Description

This phase I trial studies the side effects and best dose of modified T-cells in treating patients with Epstein-Barr virus positive lymphoma. Some types of lymphoma or lymphoproliferative disease are associated with Epstein-Barr virus. White blood cells that are treated in the laboratory with Epstein-Barr virus may be an effective treatment for lymphoma or lymphoproliferative disease.

Eligibility Criteria

Inclusion Criteria

  • INCLUSION CRITERIA AT TIME OF PROCUREMENT:
  • Any patient, regardless of age or sex, with EBV-positive Hodgkin’s or non-Hodgkin’s lymphoma, (regardless of the histological subtype) or EBV (associated)-T/NK-lymphoproliferative disease or severe chronic active EBV (CAEBV); 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 Richter’s 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)
  • EBV positive tumor (can be pending)
  • Weighs at least 12kg
  • Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent
  • INCLUSION CRITERIA AT TIME OF INFUSION:
  • Any patient, regardless of age or sex, with EBV-positive Hodgkin’s or non-Hodgkin’s lymphoma (regardless of histologic subtype), or EBV (associated)-T/NK-lymphoproliferative disease or severe chronic active EBV (CAEBV) and; 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 Richter’s transformation of CLL (Group A); patients with relapsed or refractory lymphoma that are eligible for a stem cell transplant will not be treated on this study as an alternative to transplant; OR in remission or with minimal residual disease status after autologous or syngeneic SCT (Group B)
  • EBV positive tumor
  • Patients with life expectancy >= 6 weeks
  • Bilirubin =< 3 x upper limit of normal
  • Aspartate aminotransferase (AST) =< 5 x upper limit of normal
  • Hemoglobin (Hgb) > 8.0 (may be a transfused value)
  • Creatinine =< 2 x upper limit of normal for age
  • Pulse oximetry of > 90% on room air
  • Patients should have been off other investigational therapy for 4 weeks prior to entry in this study
  • Patients with a Karnofsky/Lansky score of >= 50
  • Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded; the male partner should use a condom
  • Informed consent explained to, understood and signed by patient/guardian; patient/guardian given copy of informed consent

Exclusion Criteria

  • EXCLUSION CRITERIA AT TIME OF PROCUREMENT:
  • Active infection with human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV) (can be pending at this time)
  • EXCLUSION CRITERIA AT TIME OF INFUSION:
  • Pregnant or lactating
  • Severe intercurrent infection
  • Current use of systemic corticosteroids > 0.5 mg/kg/day

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Helen Elisabeth Heslop
Phone: 713-798-1354
Email: burton@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety of escalating doses of 2 intravenous injections of autologous rapid latent membrane protein (LMP), BamHI A rightward open-reading frame-1 (BARF1), and Epstein-Barr nuclear antigen 1 (EBNA1) specific cytotoxic T-lymphocytes (CTL) in patients with EBV-associated Hodgkin’s disease or non-Hodgkin’s lymphoma or T/natural killer (NK)-lymphoproliferative disease and chronic active EBV (CAEBV).

II. To determine the survival and the immune function of LMP/BARF1/EBNA1-specific cytotoxic T-lymphocyte lines.

III. To assess the anti-viral and anti-tumor effects of LMP/BARF1/EBNA1-specific CTL.

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

OUTLINE: This is a dose-escalation study.

Patients receive autologous LMP/BARF1/EBNA1-specific cytotoxic T-lymphocytes intravenously (IV) over 1-10 minutes on days 0 and 14. Patients with stable disease or a partial response at 8 weeks may receive up to 6 additional doses of CTLs at intervals at least 6 weeks apart.

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

Trial Phase & Type

Trial Phase

Phase I

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 H-29617
Secondary IDs NCI-2013-01016, GRALE
Clinicaltrials.gov ID NCT01555892