Cytomegalovirus InfectionsPhase 1NCT01274377
Trial of CMV Specific DLIs From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allo SCT
A Phase 1 study testing CMV Specific T Cell donor lymphocyte infusion in people with Cytomegalovirus Infections, run by Nelson Chao at 1 site in United States.
Trial summary
Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in immunocompromised individuals, such as recipients of stem cell transplants, this virus is a major cause of morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- CMV Specific T Cell donor lymphocyte infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to 5 Oct 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects who have undergone a non-myeloablative allogeneic transplant, using a 3-6/6 Human Leukocyte Antigen (HLA) matched related donor.
- Subjects must be CMV seropositive prior to transplant by CMV immune screen or CMV IgG or develop detectable disease by PCR in the post-transplant setting.
- Performance status must be Karnofsky 50-100%.
- Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure and prior to the first infusion.
- ≤ Grade 1 acute graft versus host disease (GVHD) at time of the CMV specific T cell infusion. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned donor cell infusion). The dosage level of immunosuppressive therapy at the time of infusion should be no greater than 20 mg of prednisone daily or mycophenolate 1000 mg tid daily or cyclosporine with a target level of 200 ng/ml or equivalent.
- At the time of the CMV specific T cell infusion, the recipient must have adequate organ function as indicated by < Grade 3 across all organ systems except for hematologic toxicity.
- Subject must be at least 18 years of age.
Who cannot join
- Pregnant or lactating women,
- Subjects with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise compliance with this protocol.
- Subjects who had histopathologically confirmed overall Grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible.
- Donor Inclusion/Exclusion Criteria
- Adult donors must be the same donor used for the non-myeloablative allogeneic transplant and must be a related family member with a HLA 3-6/6 match with the subject and must be capable of providing informed consent; Potential donors under the age of 18 must have a 'single patient exemption' approved by the Institutional Review Board (IRB) and the donor and a guardian must provide assent. The donor must be the same donor used for the original allogeneic transplantation. Selection of donors will be compliant with 21 CFR 1271.
- Adult donors must be CMV seropositive prior to transplant by CMV immune screen or CMV IgG positive.
- Donors will complete the Adult Donor History Questionnaire and have all laboratory studies included in the Donor Referral NTL Panel, CBC with auto or manual differential, and a Chemistry Panel within 7 days of scheduled collection procedure. Donors who were evaluated greater than 1 year prior for transplant collection will also have a history and Physical Exam, CXR, and EKG completed. Donors must not have any medical condition which would make apheresis more than a minimal risk, and should have normal range laboratory findings. All abnormal laboratory findings will be evaluated by the treating physician within the context of the entire donor assessment process.
- Females of childbearing potential should have a negative serum beta-HCG (human chorionic gonadotropin) test within 1 week of beginning apheresis.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Official title: A Pilot Trial of CMV Specific Donor Lymphocyte Infusions From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation
Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in immunocompromised individuals, such as recipients of stem cell transplants, this virus is a major cause of morbidity and mortality. While pharmacologic agents exist to treat CMV disease, these medications have numerous side effects, the most serious of which is myelosuppression. The frequency of neutropenia ranges from 41% to 58% in stem cell transplant (SCT) patients treated with ganciclovir. Withdrawal of anti-CMV therapy due to these complications may result in recurrent disease. The restoration of cellular immunity to CMV is necessary in order to prevent viral reactivation, and the generation of cytotoxic T cells against CMV early antigens is perhaps the most important part of the host immune response to CMV. At day 40 post-transplant, for example, at least 65% of SCT patients are deficient in CD8+ T-cell responses to CMV. Previous studies have demonstrated a direct correlation between CMV infection in these patients and cytotoxic T lymphocyte (CTL) function, with patients who have defects in cellular immunity being at high risk for invasive CMV disease. The median time post-transplant for the development of CMV disease is 50 to 60 days, and CMV re-activation occurs in 70 to 80% of CMV sero-positive SCT recipients. Without anti-viral therapy as many as 50% of these patients will develop CMV disease.
Read the detailed description
This protocol will evaluate the safety of CMV specific T cell infusion following nonmyeloablative stem cell transplantation from 3-6/6 HLA matched donors as well as evaluate the efficacy of antigen specific T cell infusions in preventing CMV activation.
- Conditions
- Cytomegalovirus Infections
- Being tested
- CMV Specific T Cell donor lymphocyte infusion
- Keywords
- nonmyeloablative allogeneic stem cell transplantation, cytomegalovirus, donor lymphocyte infusions, cytotoxic T lymphocyte
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV Specific T Cell donor lymphocyte infusionBiological
Also called Miltenyi Biotec
Donor Lymphocyte Infusion (DLI)
| Study group | Role | What they receive |
|---|---|---|
| Recipients Using 3-5/6 Matched Donors | Experimental | There will be an equal number of subjects (10) receiving transplants from 3-5/6 Human Leukocyte Antigen (HLA) Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 20 subjects on study. Receives: Biological: CMV Specific T Cell donor lymphocyte infusion |
| Recipients Using 6/6 Matched Donors | Experimental | There will be an equal number of subjects (10) receiving transplants from 3-5/6 HLA Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 20 subjects on study. Receives: Biological: CMV Specific T Cell donor lymphocyte infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of CMV Specific T cell infusion following Stem Cell Transplant
Donor Lymphocyte Infusion (DLI) of CMV Specific T cell clones following nonmyeloablative allogeneic stem cell transplant for the prevention of CMV
Measured: 2 years
Secondary outcomes (2)
Efficacy of CMV-specific T cell infusion in terms of response, progression free survival, and overall survival
The efficacy and its effect on survivability will be assessed.
Measured: 2 years
Evaluate the recovery of immune function post engraftment with this regimen.
Blood samples will be collected for immune reconstitution studies, including assessing CMV specific responses, just prior to each cell infusion, and 3,6, 12 months post last infusion.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2011 (estimated)
- Study startFeb 2011
- Primary completion23 Feb 2015
- Study completion5 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nelson Chao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nelson Chao, Duke University
- Investigators
- Nelson Chao, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01274377
- Sponsor's protocol ID
- Pro00013947
- Status last verified
- Jun 2017
- First submitted
- 9 Jan 2011
- Last updated
- 5 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of CMV Specific Donor Lymphocyte Infusions From 3-6/6 HLA Matched Family Member Following Nonmyeloablative Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01274377
- Acronym / sponsor ID
- Pro00013947
- Conditions
- Cytomegalovirus Infections
- Keywords
- nonmyeloablative allogeneic stem cell transplantation, cytomegalovirus, donor lymphocyte infusions, cytotoxic T lymphocyte
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Nelson ChaoUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- 23 Feb 2015 (actual)
- Study completion
- 5 Oct 2015 (actual)
- First posted
- 11 Jan 2011 (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.
Human cytomegalovirus (CMV) is a benign infectious agent in the normal host, but in immunocompromised individuals, such as recipients of stem cell transplants, this virus is a major cause of morbidity and mortality. While pharmacologic agents exist to treat CMV disease, these medications have numerous side effects, the most serious of which is myelosuppression. The frequency of neutropenia ranges from 41% to 58% in stem cell transplant (SCT) patients treated with ganciclovir. Withdrawal of anti-CMV therapy due to these complications may result in recurrent disease. The restoration of cellular immunity to CMV is necessary in order to prevent viral reactivation, and the generation of cytotoxic T cells against CMV early antigens is perhaps the most important part of the host immune response to CMV. At day 40 post-transplant, for example, at least 65% of SCT patients are deficient in CD8+ T-cell responses to CMV. Previous studies have demonstrated a direct correlation between CMV infection in these patients and cytotoxic T lymphocyte (CTL) function, with patients who have defects in cellular immunity being at high risk for invasive CMV disease. The median time post-transplant for the development of CMV disease is 50 to 60 days, and CMV re-activation occurs in 70 to 80% of CMV sero-positive SCT recipients. Without anti-viral therapy as many as 50% of these patients will develop CMV disease.
Detailed description
This protocol will evaluate the safety of CMV specific T cell infusion following nonmyeloablative stem cell transplantation from 3-6/6 HLA matched donors as well as evaluate the efficacy of antigen specific T cell infusions in preventing CMV activation.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recipients Using 3-5/6 Matched Donors | Experimental | Biological: CMV Specific T Cell donor lymphocyte infusionThere will be an equal number of subjects (10) receiving transplants from 3-5/6 Human Leukocyte Antigen (HLA) Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 20 subjects on study. |
| Recipients Using 6/6 Matched Donors | Experimental | Biological: CMV Specific T Cell donor lymphocyte infusionThere will be an equal number of subjects (10) receiving transplants from 3-5/6 HLA Matched Donors as those receiving transplants from 6/6 HLA Matched Donors for a total of 20 subjects on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects who have undergone a non-myeloablative allogeneic transplant, using a 3-6/6 Human Leukocyte Antigen (HLA) matched related donor.
- Subjects must be CMV seropositive prior to transplant by CMV immune screen or CMV IgG or develop detectable disease by PCR in the post-transplant setting.
- Performance status must be Karnofsky 50-100%.
- Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure and prior to the first infusion.
- ≤ Grade 1 acute graft versus host disease (GVHD) at time of the CMV specific T cell infusion. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned donor cell infusion). The dosage level of immunosuppressive therapy at the time of infusion should be no greater than 20 mg of prednisone daily or mycophenolate 1000 mg tid daily or cyclosporine with a target level of 200 ng/ml or equivalent.
Key exclusion criteria (8 listed)
- Pregnant or lactating women,
- Subjects with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise compliance with this protocol.
- Subjects who had histopathologically confirmed overall Grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible.
- Donor Inclusion/Exclusion Criteria
- Adult donors must be the same donor used for the non-myeloablative allogeneic transplant and must be a related family member with a HLA 3-6/6 match with the subject and must be capable of providing informed consent; Potential donors under the age of 18 must have a 'single patient exemption' approved by the Institutional Review Board (IRB) and the donor and a guardian must provide assent. The donor must be the same donor used for the original allogeneic transplantation. Selection of donors will be compliant with 21 CFR 1271.
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 |
|---|---|---|
| CMV Specific T Cell donor lymphocyte infusionAlso: Miltenyi BiotecDonor Lymphocyte Infusion (DLI) | Biological | Recipients Using 3-5/6 Matched Donors, Recipients Using 6/6 Matched Donors |
Primary outcome
Safety of CMV Specific T cell infusion following Stem Cell Transplant
Time frame: 2 years
Donor Lymphocyte Infusion (DLI) of CMV Specific T cell clones following nonmyeloablative allogeneic stem cell transplant for the prevention of CMV
2 secondary outcomes
Efficacy of CMV-specific T cell infusion in terms of response, progression free survival, and overall survival
Time frame: 2 years
Evaluate the recovery of immune function post engraftment with this regimen.
Time frame: 2 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
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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.
Nelson Chao, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CMV Specific T Cell donor lymphocyte infusion in people with Cytomegalovirus Infections, run by Nelson Chao at 1 site 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 7 inclusion and 8 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: stopped early, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was stopped early. Results are not available in the source record.
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 CMV Specific T cell infusion following Stem Cell Transplant (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jun 2017.