CMV ReactivationPhase 1/2NCT01326273
Autologous Cytomegalovirus (CMV) Specific CD8+ T Cells as Treatment for CMV Reactivation
A Phase 1/2 study testing Lymphopheresis, CMV specific lymphocyte infusion and Peripheral blood for CMV DNA PCR in people with CMV Reactivation and Allogeneic Stem Cell Transplantation, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The investigators will assess whether the infusion of autologous CMV-specific T-cells at the time of CMV reactivation posttransplant will prevent worsening of CMV virus reactivation posttransplant to a level that warrants therapy with antiviral drugs (objectively assessed by looking at CMV virus copy number). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CMV Reactivation, Allogeneic Stem Cell Transplantation, Autologous CMV Specific CD8+ T Cells
- What is being tested?
- Lymphopheresis, CMV specific lymphocyte infusion and Peripheral blood for CMV DNA PCR
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2011to Jun 2014
- Phase
- Phase 1/2
- 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
- Patients must have received an allogeneic stem cell transplant from any donor, as treatment for a haematological malignancy.
- HLAA0201 positive at one allele
- CMV seropositive
- The patient must be willing and capable of donating lymphocytes for CMVspecific CD8+ T cell selection using apheresis techniques
- The patient must be in complete remission with no evidence of circulating blasts or other malignant cells
- Patient must be fit to undergo leukapheresis
Show all 13Show fewer
- Patients must have signed an informed consent form before undergoing LP prior to alloSCT
- Indications for infusion of autologous CMV specific CD8+ Tcells:
- Therapeutic: CMV disease following allogeneic stem cell transplantation
- Preemptive: CMV reactivation (by CMV DNA PCR)
- autologous CMV specific CD8+ T-cells must be infused into the patient no later than 72 following CMV reactivation.
- Steroids should be withdrawn at least 1 week before the infusion of CMVspecific CD8+ T-cell
- Patients must have signed an informed consent form before the infusion of autologous CMV specific CD8+ T-cells
Who cannot join
- Patient CMV seronegative
- No informed consent
- Patient positive at the time of LP for one of the following infectious agents: HIV, HBV, HCV,Syphilis, HTLV 1 and 2
- Patient with circulating leukemic blasts at the time of LP
- Exclusion criteria for infusion of autologous CMV specific CD8+ T cells:
- Severe GvHD (grade IIII-V) requiring full dose immunosuppressive treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Adoptive Transfer of Autologous CMV Specific CD8+ T Cells After Allogeneic Stem Cell Transplantationas Treatment for CMV Reactivation: A Phase I/II Clinical Trial.
The investigators will assess whether the infusion of autologous CMV-specific T-cells at the time of CMV reactivation posttransplant will prevent worsening of CMV virus reactivation posttransplant to a level that warrants therapy with antiviral drugs (objectively assessed by looking at CMV virus copy number).
Read the detailed description
Allogeneic Hematopoietic Stem Cell transplantation (allo-SCT) remains the only curative approach for a number of patients with hematological malignancies. However, the use of allo-SCT can expose patients to prolonged periods of immunosupression during which time viral infections can be a significant cause of morbidity and mortality.
Human cytomegalovirus (CMV) infection and reactivation still represents one of the most important and lifethreatening complications in immunocompromised patients. Prophylaxis or early treatment with antiviral drugs after CMV reactivation have reduced the mortality related to this complication. However, the antiviral drugs have many side-effects and are costly. Furthermore, CMV infection refractory to antiviral treatment after alloSCT is associated with a high mortality. A number of studies have shown the efficacy of selecting Tcells against the virus from the donor and infusing them into the recipient (adoptive transfer of immunity) to prevent or treat CMV reactivation. However this approach relies on the donor having preexisitng immunity to CMV (50% of the healthy population is CMV seronegative and therefore have no preexisting immunity against CMV). We propose an alternative approach to collect CMV specific Tcells from the seropositive recipient prior to transplantation; the autologous CMV specific T cells will then be infused back into the recipient at the time of CMV reactivation post-transplant.
This approach is especially relevant where the donor is CMV seronegative or unavailable or following the use of cord blood transplant where there is no memory T cell response to CMV.
- Conditions
- CMV Reactivation, Allogeneic Stem Cell Transplantation, Autologous CMV Specific CD8+ T Cells
- Being tested
- Lymphopheresis, CMV specific lymphocyte infusion, Peripheral blood for CMV DNA PCR, Haematology/Blood chemistry
- Keywords
- CMV, cytomegalovirus, autologous, leukemia, hematological malignancies, stem cell transplantation, CMV reactivation, adoptive therapy
- Medical subject headings
- Leukemia, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LymphopheresisProcedure or surgery
Lymphopheresis
CMV specific lymphocyte infusionProcedure or surgery
CMV specific lymphocyte infusion
Peripheral blood for CMV DNA PCRProcedure or surgery
Peripheral blood for CMV DNA PCR
Haematology/Blood chemistryProcedure or surgery
Haematology/Blood chemistry analysis, Collection of blood for ancillary laboratory tests.
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to adoptive transfer of autologous CMV-specific CD8+ T-cells
Response to CMV-specific CD8+ T-cells administration will be measured and defined as a CMV DNA PCR< 50 copies.
Measured: Up to three years
Secondary outcomes (4)
The occurrence of subsequent CMV reactivations
The occurrence of subsequent CMV reactivations.
Measured: Up to three years
Rate of complete response
The rate of complete response will be analyzed and compared to patients treated with anti-viral drugs only.
Measured: Up to three years
Rate of early complete response
The rate of early complete response will be analyzed and compared to patients treated with anti-viral drugs only.
Measured: Up to three years
Rate of subsequent CMV reactivation
The rate of subsequent CMV reactivation will be analyzed and compared to patients treated with anti-viral drugs only.
Measured: Up to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionJun 2014 (estimated)
- Study completionJun 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CMV ReactivationStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katy Rezvani, MD, Principal investigator, Imperial College Healthcare NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01326273
- Sponsor's protocol ID
- JROHH0202
- Status last verified
- Mar 2012
- First submitted
- 22 Mar 2011
- Last updated
- 8 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Transfer of Autologous CMV Specific CD8+ T Cells After Allogeneic Stem Cell Transplantationas Treatment for CMV Reactivation: A Phase I/II Clinical Trial.
- ClinicalTrials.gov ID
- NCT01326273
- Acronym / sponsor ID
- JROHH0202
- Conditions
- CMV Reactivation, Allogeneic Stem Cell Transplantation, Autologous CMV Specific CD8+ T Cells
- Keywords
- CMV, cytomegalovirus, autologous, leukemia, hematological malignancies, stem cell transplantation, CMV reactivation, adoptive therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Jun 2014 (estimated)
- First posted
- 30 Mar 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.
The investigators will assess whether the infusion of autologous CMV-specific T-cells at the time of CMV reactivation posttransplant will prevent worsening of CMV virus reactivation posttransplant to a level that warrants therapy with antiviral drugs (objectively assessed by looking at CMV virus copy number).
Detailed description
Allogeneic Hematopoietic Stem Cell transplantation (allo-SCT) remains the only curative approach for a number of patients with hematological malignancies. However, the use of allo-SCT can expose patients to prolonged periods of immunosupression during which time viral infections can be a significant cause of morbidity and mortality.
Human cytomegalovirus (CMV) infection and reactivation still represents one of the most important and lifethreatening complications in immunocompromised patients. Prophylaxis or early treatment with antiviral drugs after CMV reactivation have reduced the mortality related to this complication. However, the antiviral drugs have many side-effects and are costly. Furthermore, CMV infection refractory to antiviral treatment after alloSCT is associated with a high mortality. A number of studies have shown the efficacy of selecting Tcells against the virus from the donor and infusing them into the recipient (adoptive transfer of immunity) to prevent or treat CMV reactivation. However this approach relies on the donor having preexisitng immunity to CMV (50% of the healthy population is CMV seronegative and therefore have no preexisting immunity against CMV). We propose an alternative approach to collect CMV specific Tcells from the seropositive recipient prior to transplantation; the autologous CMV specific T cells will then be infused back into the recipient at the time of CMV reactivation post-transplant.
This approach is especially relevant where the donor is CMV seronegative or unavailable or following the use of cord blood transplant where there is no memory T cell response to CMV.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have received an allogeneic stem cell transplant from any donor, as treatment for a haematological malignancy.
- HLAA0201 positive at one allele
- CMV seropositive
- The patient must be willing and capable of donating lymphocytes for CMVspecific CD8+ T cell selection using apheresis techniques
- The patient must be in complete remission with no evidence of circulating blasts or other malignant cells
Key exclusion criteria (6 listed)
- Patient CMV seronegative
- No informed consent
- Patient positive at the time of LP for one of the following infectious agents: HIV, HBV, HCV,Syphilis, HTLV 1 and 2
- Patient with circulating leukemic blasts at the time of LP
- Severe GvHD (grade IIII-V) requiring full dose immunosuppressive treatment
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 |
|---|---|---|
| LymphopheresisLymphopheresis | Procedure or surgery | – |
| CMV specific lymphocyte infusionCMV specific lymphocyte infusion | Procedure or surgery | – |
| Peripheral blood for CMV DNA PCRPeripheral blood for CMV DNA PCR | Procedure or surgery | – |
| Haematology/Blood chemistryHaematology/Blood chemistry analysis, Collection of blood for ancillary laboratory tests. | Procedure or surgery | – |
Primary outcome
Response to adoptive transfer of autologous CMV-specific CD8+ T-cells
Time frame: Up to three years
Response to CMV-specific CD8+ T-cells administration will be measured and defined as a CMV DNA PCR< 50 copies.
4 secondary outcomes
The occurrence of subsequent CMV reactivations
Time frame: Up to three years
Rate of complete response
Time frame: Up to three years
Rate of early complete response
Time frame: Up to three years
Rate of subsequent CMV reactivation
Time frame: Up to three years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.
Related trials for CMV Reactivation
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia
RecruitingEarly Phase 1
Donor Virus-Specific CMV or AdV CTL to Treat CMV or AdV Reactivation or Disease After Solid Organ or HCT
Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Cytomegalovirus
RecruitingPhase 3
Phase 3 Randomized Trial for Refractory ADV or CMV Infection With Family Matched CTLs and Standard of Care (SOC) vs SOC Alone
CMV, AdV Infection
RecruitingPhase 1/2
Donor-Derived Viral Specific T-cells (VSTs)
Allogeneic Stem Cell Transplant, Viral Infection
RecruitingPhase 2
Third Party Viral Specific T-cells (VSTs)
Viral Infection, Viral Reactivation
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.
Katy Rezvani, MD principal investigator
Imperial College Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lymphopheresis, CMV specific lymphocyte infusion and Peripheral blood for CMV DNA PCR in people with CMV Reactivation and Allogeneic Stem Cell Transplantation, run by Imperial College London at 1 site in United Kingdom.
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 13 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: withdrawn, as of the sponsor's last update on 8 Jun 2015. 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 Kingdom. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Response to adoptive transfer of autologous CMV-specific CD8+ T-cells (time frame: Up to three 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 8 Jun 2015.