Giving Epstein-Barr Virus (EBV) Specific Killer T Lymphocytes to Patients Who Have Had Donor Marrow Grafts

Epstein-Barr Virus Infections Clinical Trial

— ETNA  

Official title:

Administration of EBV Specific Cytotoxic T Lymphocytes to Recipients of Mismatched-Related or Phenotypically Similar Unrelated Donor Marrow Grafts

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00058812
• Other study ID #: 6676-ETNA
• Secondary ID: ETNA
• Status: Completed
• Phase: Phase 1
• First received: April 11, 2003
• Last updated: January 27, 2015
• Start date: May 1993
• Est. completion date: July 2014

Study information

• Verified date: January 2015
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Patients have a type of blood cell cancer or other blood problem that is very hard to cure with standard treatments and s/he will receive a bone marrow transplant. If the patient does not have a brother or sister whose marrow is a "perfect match", this bone marrow will come from a donor whose marrow is the best match available. This person may be a close relative or an unrelated person whose bone marrow best "matches" the patient's, and who agrees to donate marrow.

In normal people, the Epstein-Barr (EB) virus infection causes a flu like illness and usually gets better when the immune system controls the infection. The virus, however, remains hidden in the body for life. After a transplant, while the new immune system is growing back, the EB virus can come out and infect cells and cause them to grow in an uncontrolled manner. Patients can develop fevers, swollen lymph nodes and damage to other organs such as kidneys and lungs. This infection acts like a cancer because the cells infected with EB virus grow very quickly and there is no known effective treatment. This sort of infection will occur in between 10-30% of patients receiving a transplant from a donor who is not a perfect match, and has been fatal in nearly all these cases.

This infection occurs because the immune system cannot control the growth of the cells. We want to see if we can prevent it from happening or treat it by giving the patient a kind of white blood cell called T cells that we have grown from the marrow donor. These cells have been trained to attack EB virus infected cells. We will grow these T cells from blood taken from the donor at the time of bone marrow harvest. These T cells will be stimulated with the donor's EB virus-infected cells which have been treated with radiation so they cannot grow. After mixing these cells together we will be able to grow special T cells from the donor that can attack EB virus infected cells. We will then collect the T cells and make sure they can kill the virus infected cells. These EBV specific T cells are an investigational product not approved by the Food and Drug Administration.

Description:

We will obtain blood from the donor and will first make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95. We will then use this EBV-infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. We will then test the T cells to make sure that they kill the EBV infected cells and not the normal cells and freeze them.

The marrow donor's T cells will be thawed and injected through an intravenous line for a period of 10 minutes. The subject may be premedicated with diphenhydramine (Benadryl) and acetaminophen (Tylenol). We would give one dose of the cells on or after day 45 following transplant if the subject agreed and was well enough. If the EBV DNA levels remain high or the subject has persistent disease, s/he may be eligible to receive up to 5 additional injections of T cells at the original dose at monthly intervals. After the subject has received the T cells, s/he will be contacted by the research nurse or another member of the study team weekly for 6 weeks, then once every three months for a year so that we can check on his/her progress.

We will continue to follow the subject in the BMT clinic after the injections. To learn more about the way the T cells are working, an extra 40 mls (about 8 teaspoonfuls) of blood will be taken pre-infusion, 4 hours after the infusion, 3-4 days post infusion (optional) and at 1, 2, 4 and 6 weeks after the T cell infusions, and then at 3, 6, 9, and 12 months post infusion. The blood should come from the central intravenous line, and should not require extra needle sticks.

Other known NCT identifiers

• NCT00608309

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

INCLUSION CRITERIA:

• All patients receiving a T cell depleted BMT from a mismatched family member or unrelated donor will be eligible for this protocol. In addition, patients receiving a matched sibling transplant or T replete transplant may be eligible if they are at high risk of developing EBV LPD because of their underlying disease (e.g Wiskott-Aldrich or Ataxia Telangiectasia) or have a past history of EBVLPD or other EBV associated malignancy.

• O2 saturation > 90% on room air

EXCLUSION CRITERIA:

• Exclusion criteria for BMT will be as detailed in the relevant protocol.

Exclusion criteria at time of administration CTLs:

• Patients with GVHD of Grade II or greater.

• Patients with severe renal disease (i.e., creatinine clearance less than half normal for age).

• Patients with severe hepatic disease (bilirubin greater than twice normal, or SGOT greater than 3 x normal).

• Patients with a severe intercurrent infection.

• Patients with a life expectancy <6 weeks

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epstein-Barr Virus Infections
• Virus Diseases

Intervention

Biological:
• EBV specific T cells
One injection of 2x10^7 cells/m2 from Day 45 post transplant. If EBV DNA levels remain elevated above 1000 copies/ug or the patient has persistent disease they will be eligible to receive up to 5 additional injections of CTLs at the original dose at monthly intervals.

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas

Sponsors (4)

Lead Sponsor	Collaborator
Baylor College of Medicine	Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of one intravenous injection of BMT donor derived EBV specific cytotoxic T lymphocytes (CTLs) in BMT recipients at high risk.		1 year	Yes
Primary	To compare the antiviral and immunological efficacy of a single dose of CTLs compared to the multiple dose regimens previously employed		1 year	No