Autologous or Donor Cytotoxic T-Cells in Treating Patients With Epstein-Barr Virus-Positive Lymphoma, Lymphoepithelioma, or Lymphoproliferative Disorder
The purpose of this study is to find the largest safe dose of transforming growth factor-beta (TGFb) resistant latent membrane protein (LMP)-specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease, non-Hodgkin lymphoma and lymphoepithelioma.
- Any patient, regardless of age or sex, with Epstein-Barr virus (EBV)-positive lymphoma, or lymphoepithelioma regardless of the histological subtype or EBV (associated)-T/natural killer (NK)-lymphoproliferative disorder (LPD) all confirmed on any tissue sample * Primary refractory lymphoma or in second or subsequent relapse including after autologous or syngeneic stem cell transplant OR patients at a high risk for relapse defined as: (i) patients with primary refractory lymphoma or multiply relapsed lymphoma who are in remission but not eligible for autologous stem cell transplant (SCT) or (ii) patients with relapsed lymphoma after autologous SCT who are in remission but not eligible for allogeneic SCT (Group A) OR * Any patient who has received an allogeneic SCT for EBV lymphoma or EBV (associated)-T/NK-LPD or lymphoepithelioma (Group B)
- Patients with life expectancy >= 6 weeks from time of CTL infusion
- Patients with a Karnofsky score of >= 50
- If post allogeneic SCT must not have less than 50% donor chimerism in either peripheral blood or bone marrow
- Patients with bilirubin =< 3 x normal
- Aspartate aminotransferase (AST) =< 5 x normal
- Hemoglobin (Hgb) > 8.0
- Patients with a creatinine =< 2 x normal for age
- Patients with oxygen (O^2) saturations > 93% on room air (measured by pulse oximetry)
- Patient, parent/guardian able to give informed consent
- Patients should have been off other investigational therapy for one month prior to entry in this study
- Patients with a severe intercurrent infection
- Patients with evidence of graft versus host disease (GVHD) > grade II at time of enrollment
- Human immunodeficiency virus (HIV) positive at time of procurement cells for CTL generation
- Pregnant women are excluded from this research; the male partner should use a condom
Locations & Contacts
Trial Objectives and Outline
I. To determine the safety of 2 intravenous injections of autologous or allogeneic TGF-beta-resistant LMP-specific cytotoxic T-lymphocytes (CTL) in patients with relapsed Hodgkin’s or non-Hodgkin’s lymphoma.
II. To determine the survival and the immune function of TGF-beta-resistant LMP specific cytotoxic T-lymphocyte lines.
III. To assess the anti-viral and anti-tumor effects of TGF-beta-resistant LMP-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 2 doses of autologous or allogeneic TGF-beta-resistant LMP-specific cytotoxic T-lymphocytes intravenously (IV) over 1-10 minutes administered 14 days apart. Patients achieving stable disease or partial response at 6 weeks may receive up to 6 additional doses every 1-2 months until achievement of complete response in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed up at 1, 2, 4, and 6 weeks, every 3 months for 1 year, at 1.5 years, every 6 months for 4 years, and then yearly for a total of 15 years.
Trial Phase & Type
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Helen Elisabeth Heslop
Secondary IDs NCI-2012-00654, TGFb
Clinicaltrials.gov ID NCT00368082