Epstein Barr Virus (EBV) Specific Cytotoxic T-Cells, Relapsed Lymphoma, ANGEL

NCT00058617 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 6423-ANGELANGEL
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

Patients have a type of lymph gland cancer called Hodgkin or non-Hodgkin Lymphoma which has come back or not gone away after treatment, including the best treatment known for relapsed Lymphoma. Patients are being asked to volunteer to be in a research study using Epstein Barr virus specific cytotoxic T lymphocytes, a new experimental therapy. This therapy has never been used in patients with Hodgkin disease or this type of non-Hodgkin Lymphoma but it has been used successfully in children with other types of blood cancer caused by EBV after bone marrow transplantation. Some patients with Hodgkin or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus before or at the time of their diagnosis of the Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. Investigators want to see if it's possible to grow special white blood cells, called T cells, that have been trained to kill EBV infected cells. Purpose The purpose of this study is to find the largest safe dose of EBV specific cytotoxic T cells, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease and non-Hodgkin Lymphoma.

Conditions

Epstein-Barr Virus-Related Hodgkin Lymphoma; Epstein-Barr Virus-Related Non-Hodgkin Lymphoma; EBV Positive Plasma Cell Neoplasm

Keywords

EBV Positive Hodgkin's Lymphoma; EBV Positive Non-Hodgkin's Lymphoma; EBV Specific Cytotoxic T-Lymphocytes

Outcome Measures

Primary Outcomes (3)

• The safety of two IV injections of auto EBV specific CTLs will be determined through adverse event measurement. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector.

  Three patients will be enrolled at the first dose level and followed for six weeks after the second dose (which will constitute a course) for evaluation of any critical toxicity. The toxicity will be evaluated as per the NCI Common Toxicity criteria version 2.0.Any toxicity scored as Grade 3 or 4 according to this criteria will be classified as an adverse event. If no toxicity is observed in the first three patients then we will enroll another three patients at the next dose level. However, if toxicity is observed in no more than one out of the three patients then three more patients will be enrolled at the same dose level. Now if the toxicity is observed in no more than one out of the six patients then we will advance to the next dose level and enroll three new patients. If toxicity is observed in two or more patients out of six then the dose limiting toxicity (DLT) has been exceeded and the previous dose level will be considered as the maximum tolerated dose (MTD) level.

  6 weeks

• To determine the feasibility of generating EBV specific cytotoxic T cell lines from patients with active EBV positive Lymphoma including Hodgkin Disease (HD) or Non-Hodgkin Lymphoma (NHL).

  6 weeks

• To determine the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines.

  During the course of the study the survival, immunological efficacy and anti-tumor activity of neomycin resistance gene marked EBV specific cytotoxic T-lymphocyte lines will also be studied. In order to gain reasonable insight into the anti-tumor activity and late toxicity the patients will be followed for a total of twelve weeks.In the present case, the chances of observing any late toxicity should be if anything lower, as in this case the CTLs will be derived autologously.

  15 years

Study Arms (1)

Injection of EBV Specific CTLs

EXPERIMENTAL

Subjects will receive autologous EBV Specific CTLs. Patients that agree will recieve CTLs that have been marked with the neomycin resistance gene.

Biological: Injection of EBV Specific CTLs

Interventions

Injection of EBV Specific CTLs BIOLOGICAL

Each patient will receive two injections, 14 days apart, according to the following dosing schedules: Group One Day 0 2x10\^7 cells/m2 Day 14 2x10\^7 cells/m2 Group Two Day 0 2x10\^7 cells/m2 Day 14 1x10\^8 cells/m2 Group Three Day 0 1x10\^8 cells/m2 Day 14 2x 10\^8 cells/m2 If patients with active disease have stable disease or a partial response by the RECIST criteria at their 8 week or subsequent evaluations they are eligible to receive up to 6 additional doses of CTLs at monthly intervals-each of which will consist of the same cell number as their second injection. Patients will not be able to receive additional doses until the initial safety profile is completed at 6 weeks following the second infusion.

Injection of EBV Specific CTLs

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with EBV positive Hodgkin disease or non-Hodgkin Lymphoma, or plasma cell neoplasms in second relapse regardless of age or sex, in first relapse or with primary disease or in first remission if immunosuppressive chemotherapy 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 CLL.
• Life expectancy of greater than 6 weeks.
• No severe intercurrent infection
• Patient, parent/guardian able to give informed consent
• Bilirubin \<2x normal,
• SGOT \<3x normal,
• Hgb greater than 8.0 g/L
• Creatinine \<2x normal for age
• Must have been off other investigational therapy for one month prior to entry in this study.
• Karnofsky score of greater than or equal to 50.

You may not qualify if:

• Patient with an EBV positive NHL secondary to an acquired immunodeficiency.
• Patients who are HIV positive
• Patient, parent/guardian unable to give informed consent
• Patients with a Karnofsky score of \< 50.
• Patients with a life expectancy of \<6 weeks
• Patients with a bilirubin greater than 2x normal. SGOT greater than 3x normal
• Patients with a creatinine greater than 2x normal for age
• Due to unknown effects of this therapy on a fetus, 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 CCGT Protocol Review Committee and the FDA reviewer.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Study Officials

• Helen E Heslop, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2003
• First Posted: April 9, 2003
• Study Start: January 1, 1996
• Primary Completion: August 1, 2011
• Study Completion: July 1, 2014
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (2)