Adenovirus InfectionPhase 1LYPTAISTNCT00590083
Administration of Virus-Specific Cytotoxic T-Lymphocytes
A Phase 1 study testing CTL administration in people with Adenovirus Infection, run by Baylor College of Medicine at 3 sites in United States.
Trial summary
The main purpose of this study is to see if these T-lymphocytes are safe. To make these Ad-specific T lymphocytes the investigators will obtain blood from the stem cell donor and transfer Ad into another type of blood cell, called monocytes. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Adenovirus Infection
- What is being tested?
- CTL administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2003to Jan 2011
- 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
- Recipients of allogeneic (i.e. HLA matched or mismatched related or unrelated) donor stem cell transplants at risk for Adenoviral disease
- No evidence of GVHD > Grade II at time of enrollment
- Life expectancy > 30 days
- No severe intercurrent infections
- Lansky/Karnofsky scores >60
- Absence of severe renal disease (Creatinine > x 3 normal for age)
Show all 11Show fewer
- Absence of severe hepatic disease (direct bilirubin > 3 mg/dl or SGOT > 500)
- Patient must be at least 30 days post transplant to be eligible to receive CTL
- Not receiving Cidofovir
- Patient has not received other viral specific CTL prophylactically within 4 weeks of receiving Adv-CTL
- Patient/guardian able to give informed consent
Who cannot join
- Patients with GVHD Grades III-IV
- Patients with hepatic or renal disease as specific above
- Patient has received other viral specific CTL (e.g. EBV-specific CTL or CMV-specific CTL) within 4 weeks of receiving Adv-CTL
- Patients with Adenoviral disease prior to day +30 post transplant Adenoviral diseases defined as the presence of more than two sites positive for adenovirus by culture
- Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Texas Children's Hospital
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
National Institute of Health (NIH)
Washington D.C., District of Columbia, 20894
About this study
Official title: Administration of Virus-Specific Cytotoxic T-Lymphocytes for the Prophylaxis and Therapy of Adenovirus Infection Post Allogeneic Stem Cell Transplant
The main purpose of this study is to see if these T-lymphocytes are safe. To make these Ad-specific T lymphocytes the investigators will obtain blood from the stem cell donor and transfer Ad into another type of blood cell, called monocytes. These cells can then stimulate the T lymphocytes and train them to kill cells infected with Ad. The investigators will then grow these Ad-specific T lymphocytes by more stimulation with Ad-infected monocytes and a third type of blood cell called a B lymphoblast from the donor. After testing the T -lymphocytes, the investigators will inject them into patients after transplant who are at high risk of serious Ad virus infection. The investigators will make sure the injected cells are safe and see if they affect the growth and behavior of adenoviruses in the patient's own body.
Read the detailed description
Viral infection is one of the major causes of morbidity and mortality in patients who receive bone marrow transplantation (BMT) from unrelated or mismatched donors. This increased risk of infection relates to a number of factors including the immunosuppressive regimens these patients receive, delayed immune recovery and the greater genetic disparity between donor and recipient that result in defective interactions between antigen presenting cells and immune system effector cells. In most cases viral infection post BMT results from reactivation of latent virus and CMV, EBV and adenoviruses (Ad) are the commonest viral pathogens causing disease after transplant.
The incidence of Ad infection is >25% for patients at risk in the first 100 days after transplant 1 2. In the transplant population, adenovirus is recoverable from many sites and may cause hemorrhagic cystitis, pneumonitis, nephritis, hepatitis, colitis and pancreatitis, often with severe morbidity and a mortality approaching 60%3. The most frequently used drug for the treatment of adenoviral infections is Cidofovir. But while there are occasional reports of responses to Cidofovir, no approved antiviral agent has proven efficacy for the treatment of severe Ad disease, nor are there any prospective randomized, controlled trials of potentially useful anti-Ad therapies 4. With the increasing use of so-called submyeloablative or reduced intensity, highly immunosuppressive conditioning regimens, higher rates of Ad infections/reactivation have been observed due to prolonged immune suppression. The onset of Ad disease/reactivation has recently been reported to occur at a median of 18 days post-transplant (range -7/>+100) 2.
As viral complications in these patients are clearly associated with the lack of recovery of virus-specific cellular immune responses, reconstitution of the host with in vitro expanded CTLs is an effective approach to prevent and treat these diseases. Adoptive immunotherapy with in vitro expanded CTLs has proved effective in preventing and treating diseases related to Epstein Barr virus (EBV) infections 5; 6 and cytomegalovirus (CMV) reactivations7 in hematopoietic stem cell transplant (HSCT) recipients. A promising strategy to generate donor-derived Ad-specific CTL is the infection of monocytes that direct the CTL response to viral capsid antigens8. This approach allows exposure to all proteins in the Ad protein coat, leading to presentation of multiple, undefined antigen epitopes. Hence, the investigators now plan to use a recombinant Ad vector for infection of donor-derived monocytes. These infected monocytes will then be used as antigen presenting cells (APC) to generate Ad-specific CTL in vitro. For the expansion of the Ad-specific CTL, the second stimulation will use irradiated, Ad-infected monocytes and subsequent stimulations will use donor-derived Lymphoblastoid Cell Lines (LCL) transduced with the Ad vector as an APC 9.
The investigators propose to evaluate this approach for the prophylaxis of Ad reactivation and disease in the recipients of matched unrelated donor or mismatched family member bone marrow allografts, who are at high risk for this complication. Initially, the investigators will give the donor-derived Ad-specific CTLs to patients in a dose escalation study to determine their safety and immunologic and virologic efficacy.
- Conditions
- Adenovirus Infection
- Being tested
- CTL administration
- Keywords
- stem cell transplantation, adenovirus, Cytotoxic T-Lymphocytes, prophylaxis
- Medical subject headings
- Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTL administrationBiological
Adenovirus specific T cells will be given by intravenous injection from day 30 post transplant.
One infusion of Adenovirus-specific CTL given to patients at risk for Adenoviral disease after matched or mismatched unrelated or matched or mismatched related donor stem cell transplant. Four dose levels will be explored. The lowest level will be 1x dose of 5x10e6cells/m2 and the highest will be 1x dose of 1.35x10e8/m2.
| Study group | Role | What they receive |
|---|---|---|
| Virus Specific Cytoxic T lymphocytes | Experimental | Virus Specific Cytoxic T lymphocytes Receives: Biological: CTL administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety, toxicity and MTD of 1 IV injection of donor-derived adenovirus-specific CTLs given as adenovirus prophylaxis to patients at risk of developing adenovirus infection after allogeneic stem cell transplant.
Measured: 1 year
To evaluate the recovery of virus-specific immunity after CTL infusion and assess its correlation with protection from viral load and disease.
Measured: 1 year
To obtain preliminary information regarding whether the presence of antigen is required for Ad-specific CTL persistence in vivo.
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 posted10 Jan 2008 (estimated)
- Study startJul 2003
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenovirus InfectionStudies 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital Research Institute, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, catherine bollard, Baylor College of Medicine
- Investigators
- Catherine Bollard, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00590083
- Sponsor's protocol ID
- 14097-LYPTAIST
- Acronym
- LYPTAIST
- Status last verified
- Feb 2014
- First submitted
- 21 Dec 2007
- Last updated
- 19 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, Kennedy-Nasser AA, Leung KS, Gee AP, Krance RA, Brenner MK, Heslop HE, Rooney CM, Bollard CM. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009 Nov 5;114(19):4283-92. doi: 10.1182/blood-2009-07-232454. Epub 2009 Aug 21.
PubMed 19700662
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Virus-Specific Cytotoxic T-Lymphocytes for the Prophylaxis and Therapy of Adenovirus Infection Post Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT00590083
- Acronym / sponsor ID
- LYPTAIST / 14097-LYPTAIST
- Conditions
- Adenovirus Infection
- Keywords
- stem cell transplantation, adenovirus, Cytotoxic T-Lymphocytes, prophylaxis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital Research Institute, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jul 2003
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 10 Jan 2008 (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.
The main purpose of this study is to see if these T-lymphocytes are safe. To make these Ad-specific T lymphocytes the investigators will obtain blood from the stem cell donor and transfer Ad into another type of blood cell, called monocytes. These cells can then stimulate the T lymphocytes and train them to kill cells infected with Ad. The investigators will then grow these Ad-specific T lymphocytes by more stimulation with Ad-infected monocytes and a third type of blood cell called a B lymphoblast from the donor. After testing the T -lymphocytes, the investigators will inject them into patients after transplant who are at high risk of serious Ad virus infection. The investigators will make sure the injected cells are safe and see if they affect the growth and behavior of adenoviruses in the patient's own body.
Detailed description
Viral infection is one of the major causes of morbidity and mortality in patients who receive bone marrow transplantation (BMT) from unrelated or mismatched donors. This increased risk of infection relates to a number of factors including the immunosuppressive regimens these patients receive, delayed immune recovery and the greater genetic disparity between donor and recipient that result in defective interactions between antigen presenting cells and immune system effector cells. In most cases viral infection post BMT results from reactivation of latent virus and CMV, EBV and adenoviruses (Ad) are the commonest viral pathogens causing disease after transplant.
The incidence of Ad infection is >25% for patients at risk in the first 100 days after transplant 1 2. In the transplant population, adenovirus is recoverable from many sites and may cause hemorrhagic cystitis, pneumonitis, nephritis, hepatitis, colitis and pancreatitis, often with severe morbidity and a mortality approaching 60%3. The most frequently used drug for the treatment of adenoviral infections is Cidofovir. But while there are occasional reports of responses to Cidofovir, no approved antiviral agent has proven efficacy for the treatment of severe Ad disease, nor are there any prospective randomized, controlled trials of potentially useful anti-Ad therapies 4. With the increasing use of so-called submyeloablative or reduced intensity, highly immunosuppressive conditioning regimens, higher rates of Ad infections/reactivation have been observed due to prolonged immune suppression. The onset of Ad disease/reactivation has recently been reported to occur at a median of 18 days post-transplant (range -7/>+100) 2.
As viral complications in these patients are clearly associated with the lack of recovery of virus-specific cellular immune responses, reconstitution of the host with in vitro expanded CTLs is an effective approach to prevent and treat these diseases. Adoptive immunotherapy with in vitro expanded CTLs has proved effective in preventing and treating diseases related to Epstein Barr virus (EBV) infections 5; 6 and cytomegalovirus (CMV) reactivations7 in hematopoietic stem cell transplant (HSCT) recipients. A promising strategy to generate donor-derived Ad-specific CTL is the infection of monocytes that direct the CTL response to viral capsid antigens8. This approach allows exposure to all proteins in the Ad protein coat, leading to presentation of multiple, undefined antigen epitopes. Hence, the investigators now plan to use a recombinant Ad vector for infection of donor-derived monocytes. These infected monocytes will then be used as antigen presenting cells (APC) to generate Ad-specific CTL in vitro. For the expansion of the Ad-specific CTL, the second stimulation will use irradiated, Ad-infected monocytes and subsequent stimulations will use donor-derived Lymphoblastoid Cell Lines (LCL) transduced with the Ad vector as an APC 9.
The investigators propose to evaluate this approach for the prophylaxis of Ad reactivation and disease in the recipients of matched unrelated donor or mismatched family member bone marrow allografts, who are at high risk for this complication. Initially, the investigators will give the donor-derived Ad-specific CTLs to patients in a dose escalation study to determine their safety and immunologic and virologic efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Virus Specific Cytoxic T lymphocytes | Experimental | Biological: CTL administrationVirus Specific Cytoxic T lymphocytes |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Recipients of allogeneic (i.e. HLA matched or mismatched related or unrelated) donor stem cell transplants at risk for Adenoviral disease
- No evidence of GVHD > Grade II at time of enrollment
- Life expectancy > 30 days
- No severe intercurrent infections
- Lansky/Karnofsky scores >60
Key exclusion criteria (5 listed)
- Patients with GVHD Grades III-IV
- Patients with hepatic or renal disease as specific above
- Patient has received other viral specific CTL (e.g. EBV-specific CTL or CMV-specific CTL) within 4 weeks of receiving Adv-CTL
- Patients with Adenoviral disease prior to day +30 post transplant Adenoviral diseases defined as the presence of more than two sites positive for adenovirus by culture
- Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
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 |
|---|---|---|
| CTL administrationAdenovirus specific T cells will be given by intravenous injection from day 30 post transplant. One infusion of Adenovirus-specific CTL given to patients at risk for Adenoviral disease after matched or mismatched unrelated or matched or mismatched related donor stem cell transplant. Four dose levels will be explored. The lowest level will be 1x dose of 5x10e6cells/m2 and the highest will be 1x dose of 1.35x10e8/m2. | Biological | Virus Specific Cytoxic T lymphocytes |
Primary outcome
safety, toxicity and MTD of 1 IV injection of donor-derived adenovirus-specific CTLs given as adenovirus prophylaxis to patients at risk of developing adenovirus infection after allogeneic stem cell transplant.
Time frame: 1 year
To evaluate the recovery of virus-specific immunity after CTL infusion and assess its correlation with protection from viral load and disease.
Time frame: 1 year
To obtain preliminary information regarding whether the presence of antigen is required for Ad-specific CTL persistence in vivo.
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 19 Feb 2014.
- Derived from this study: PubMed 19700662Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, Kennedy-Nasser AA, Leung KS, Gee AP, Krance RA, Brenner MK, Heslop HE, Rooney CM, Bollard CM. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009 Nov 5;114(19):4283-92. doi: 10.1182/blood-2009-07-232454. Epub 2009 Aug 21.
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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.
Catherine Bollard, MD principal investigator
Baylor College of Medicine
3 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 CTL administration in people with Adenovirus Infection, run by Baylor College of Medicine at 3 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 11 inclusion and 5 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 19 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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, toxicity and MTD of 1 IV injection of donor-derived adenovirus-specific CTLs given as adenovirus prophylaxis to patients at risk of developing adenovirus infection after allogeneic stem cell transplant. (time frame: 1 year). The study lists 3 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 NCT00590083, which also lists 1 linked publication.
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 19 Feb 2014.