Epstein-Barr Virus InfectionsPhase 1ETNANCT00058812
Giving Epstein-Barr Virus (EBV) Specific Killer T Lymphocytes to Patients Who Have Had Donor Marrow Grafts
A Phase 1 study testing EBV specific T cells in people with Epstein-Barr Virus Infections, run by Baylor College of Medicine at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Epstein-Barr Virus Infections
- What is being tested?
- EBV specific T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 2 sitesUnited States
- Study dates
- May 1993to Jul 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Exclusion criteria for BMT will be as detailed in the relevant protocol.
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Houston Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: Administration of EBV Specific Cytotoxic T Lymphocytes to Recipients of Mismatched-Related or Phenotypically Similar Unrelated Donor Marrow Grafts
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.
Read the detailed 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.
- Conditions
- Epstein-Barr Virus Infections
- Being tested
- EBV specific T cells
- Keywords
- Cytotoxic T Lymphocytes, bone marrow transplant, EBV+ lymphoproliferative disease
- Medical subject headings
- Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EBV specific T cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| EBV specific T cells | Experimental | EBV specific T cells Receives: Biological: EBV specific T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of one intravenous injection of BMT donor derived EBV specific cytotoxic T lymphocytes (CTLs) in BMT recipients at high risk.
Measured: 1 year
To compare the antiviral and immunological efficacy of a single dose of CTLs compared to the multiple dose regimens previously employed
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2003 (estimated)
- Study startMay 1993
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Epstein-Barr Virus InfectionsStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Helen Heslop, Baylor College of Medicine
- Investigators
- Helen E Heslop, MD, Principal investigator, Center for Cell and Gene Therapy, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00058812
- Sponsor's protocol ID
- 6676-ETNA
- Other IDs
- ETNA
- Acronym
- ETNA
- Status last verified
- Jan 2015
- First submitted
- 11 Apr 2003
- Last updated
- 29 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31.
PubMed 21454450Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, Bollard CM, Liu H, Wu MF, Rochester RJ, Amrolia PJ, Hurwitz JL, Brenner MK, Rooney CM. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010 Feb 4;115(5):925-35. doi: 10.1182/blood-2009-08-239186. Epub 2009 Oct 30.
PubMed 19880495
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of EBV Specific Cytotoxic T Lymphocytes to Recipients of Mismatched-Related or Phenotypically Similar Unrelated Donor Marrow Grafts
- ClinicalTrials.gov ID
- NCT00058812
- Acronym / sponsor ID
- ETNA / 6676-ETNA
- Conditions
- Epstein-Barr Virus Infections
- Keywords
- Cytotoxic T Lymphocytes, bone marrow transplant, EBV+ lymphoproliferative disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- May 1993
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 15 Apr 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EBV specific T cells | Experimental | Biological: EBV specific T cellsEBV specific T cells |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (6 listed)
- Exclusion criteria for BMT will be as detailed in the relevant protocol.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EBV specific T cellsOne 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. | Biological | EBV specific T cells |
Primary outcome
Safety of one intravenous injection of BMT donor derived EBV specific cytotoxic T lymphocytes (CTLs) in BMT recipients at high risk.
Time frame: 1 year
To compare the antiviral and immunological efficacy of a single dose of CTLs compared to the multiple dose regimens previously employed
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2015.
- Derived from this study: PubMed 21454450Cohen JI, Jaffe ES, Dale JK, Pittaluga S, Heslop HE, Rooney CM, Gottschalk S, Bollard CM, Rao VK, Marques A, Burbelo PD, Turk SP, Fulton R, Wayne AS, Little RF, Cairo MS, El-Mallawany NK, Fowler D, Sportes C, Bishop MR, Wilson W, Straus SE. Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood. 2011 Jun 2;117(22):5835-49. doi: 10.1182/blood-2010-11-316745. Epub 2011 Mar 31.
- Derived from this study: PubMed 19880495Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, Bollard CM, Liu H, Wu MF, Rochester RJ, Amrolia PJ, Hurwitz JL, Brenner MK, Rooney CM. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010 Feb 4;115(5):925-35. doi: 10.1182/blood-2009-08-239186. Epub 2009 Oct 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen E Heslop, MD principal investigator
Center for Cell and Gene Therapy, Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EBV specific T cells in people with Epstein-Barr Virus Infections, run by Baylor College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of one intravenous injection of BMT donor derived EBV specific cytotoxic T lymphocytes (CTLs) in BMT recipients at high risk. (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00058812, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2015.