Viral InfectionPhase 1/2NCT03594981
Adoptive Cord Blood Immunotherapy for EBV, CMV, BKV and Adenovirus Reactivation/Infection or Prophylaxis
A Phase 1/2 study testing CMV/AdV /EBV/BKV specific T cells in people with Viral Infection, run by Catherine Bollard at 2 sites in United States.
Trial summary
This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Viral Infection
- What is being tested?
- CMV/AdV /EBV/BKV specific T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Jan 2018to 15 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Pediatric and adult patients (there are no lower and upper age limits for patients) with malignant or nonmalignant diseases who are candidates for transplant.
- Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit selected for CTL expansion must be either:
- be cryopreserved in two fractions, with a minimum of 2.5x107 total nucleated cells (TNC) per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below. OR
- be cryopreserved with a cell dose that totals > 3x10e7 TNC per kg pre thaw. On thaw, 20% of the total volume will be used for CTL manufacture to give at day 30 or beyond and the remaining 80% will be used for the primary transplant.
- For recipients of double CBT, if possible both CB units should be cryopreserved in two fractions and T-cells will be made from both units if possible.
- Recipients of at least one unmanipulated cord blood unit as described above (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral/BKV and/or EBV infection or reactivation.
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- Lansky/Karnofsky scores ≥60
- Absolute neutrophil count (ANC) greater than 500/u
- No evidence of GVHD > Grade II at time of enrollment
- Life expectancy > 30 days
- Absence of severe renal disease (Creatinine < 3x normal for age)
- Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal
- Patient must be at least 30 days post transplant to be eligible to receive CTL
- Written informed consent and/or signed assent line from patient, parent or guardian
Who cannot join
- Pregnant or lactating
- Patients with active central nervous system disease
- Patients with Karnofsky performance status <70%
- Patients with grade 3 or 4 or primary myelofibrosis
- Patients with suitable related donors Exclusion Criteria at the Time of CTL Infusion
- Pregnant or lactating
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- Patient on Fi02 of >60%
- Unable to wean steroids to ≤0.5 mg/kg/day prednisone or equivalent
- Patients with Grade 3 hyperbilirubinemia
- Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia and/or BK viruria/viremia). For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
- Patients who have received investigational (IND) product within 28 days of screening for CTL infusion under this study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
M.D. Anderson Cancer Center (MDACC)
Houston, Texas, 77030
Children's National Health System
Washington D.C., District of Columbia, 20010
About this study
Official title: Adoptive Cord Blood ImmunotHerapy Using Expanded Cord Blood T Cells for EBV, CMV, BKV and Adenovirus Reactivation/Infection or ProphylaxiS
This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating.
The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al.
Read the detailed description
This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating.
The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al. To implement the design's model using the latest EffTox version 4.0.12 program, doses will coded numerically to be 1, 2, 3.
CMV/AdV /EBV/BKV specific T cells will be thawed and given or thawed and diluted into a total volume of 10 mL of Plasmalyte A by slow intravenous injection over 1-2 minutes. This is a traditional Phase I dose escalation study of a single infusion of CMV/AdV/EBV/BKV-specific CTLs to patients at risk for CMV and EBV reactivation and Adenoviral and BK virus infection after umbilical cord blood transplantation. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. There will be 2-6 patients at each dose level (depending on toxicity) following the scheme below. The decision on whether it is safe to escalate to next dose level or not will be made after at least two patients in each dose level have finished their 45-days toxicity follow up. If the first two patients have not finished their 45 days follow-up, up to 2 additional incoming patients can be enrolled at the current dose level. In addition, we will give the option of administering 2 additional doses (at the same dose level), 28 days after the first infusion of the same dose, in subjects who have a partial response after one dose or who have received other therapy that may affect the persistence or function of the infused CTL in vivo. If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval.
Dose Levels and Dosing Schedule
Dose Level CTL Dose Given from Day +30 post SCT
- 1x107/m2
- 2.0x107/m2
- 5x107/m2
Escalation of Multi-virus-specific CTL infusions
CMV/AdV/EBV/BKV CTL will be given from day +30 either as prophylaxis or treatment for CMV, EBV, BK and/or adenovirus infection. If the patient has viral reactivation or evidence of CMV/EBV/AdV/BKV disease (e.g. pneumonitis, gastroenteritis and/or retinitis or Post Transplant Lymphoproliferative Disorder (PTLD) or hemorrhagic cystitis the CTL can be given with concurrent antiviral pharmacotherapy.
A dose escalation scheme utilizing cohorts of two patients will be used
Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm described in Section 9 will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual.
The Optimal Dose of Infused CMV/AdV/EBV/BKV-Specific CTL
After all patients in the trial have been evaluated, the optimal dose of infused CMV/AdV/EBV-specific CTL will be determined by the algorithm using the sequentially adaptive EffTox trade-off-based design of Thall et al.
- Conditions
- Viral Infection
- Being tested
- CMV/AdV /EBV/BKV specific T cells
- Medical subject headings
- Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV/AdV /EBV/BKV specific T cellsBiological
Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm of sequentially adaptive EffTox trade-off-based design of Thall et al will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual.
| Study group | Role | What they receive |
|---|---|---|
| CMV/AdV /EBV/BKV specific T cells | Experimental | CMV/AdV /EBV/BKV specific T cells will be thawed and transferred to a syringe given by slow intravenous injection over 1-2 minutes. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. Receives: Biological: CMV/AdV /EBV/BKV specific T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03
The study will determine the optimal dose of intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, Adenovirus and BK virus( BKV) given to patients with or at risk for CMV, EBV, BK virus and adenovirus infection after cord blood transplant. The safety will be assessed by investigational product-related adverse events as per CTCAE v4.03.
Measured: 45 days for toxicity
Secondary outcomes (1)
Impact of CMV/AdV /EBV/BKV specific T cells will be measured by existence of cells in the system.
To evaluate the impact of CTLs on CMV/AdV /EBV/BKV -specific T-lymphocyte immune reconstitution. The impact will be evaluated by the number of months/years of cell survival.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2018
- Study start24 Jan 2018
- Primary completion5 Nov 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Viral InfectionStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Bollard
- Sponsor type
- University, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor-investigator, Catherine Bollard, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03594981
- Sponsor's protocol ID
- CHEERS
- Status last verified
- Aug 2026
- First submitted
- 14 May 2018
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Cord Blood ImmunotHerapy Using Expanded Cord Blood T Cells for EBV, CMV, BKV and Adenovirus Reactivation/Infection or ProphylaxiS
- ClinicalTrials.gov ID
- NCT03594981
- Acronym / sponsor ID
- CHEERS
- Conditions
- Viral Infection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Catherine BollardUniversity, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Study start
- 24 Jan 2018 (actual)
- Primary completion
- 5 Nov 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 23 Jul 2018 (actual)
- 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.
This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating.
The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al.
Detailed description
This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating.
The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al. To implement the design's model using the latest EffTox version 4.0.12 program, doses will coded numerically to be 1, 2, 3.
CMV/AdV /EBV/BKV specific T cells will be thawed and given or thawed and diluted into a total volume of 10 mL of Plasmalyte A by slow intravenous injection over 1-2 minutes. This is a traditional Phase I dose escalation study of a single infusion of CMV/AdV/EBV/BKV-specific CTLs to patients at risk for CMV and EBV reactivation and Adenoviral and BK virus infection after umbilical cord blood transplantation. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. There will be 2-6 patients at each dose level (depending on toxicity) following the scheme below. The decision on whether it is safe to escalate to next dose level or not will be made after at least two patients in each dose level have finished their 45-days toxicity follow up. If the first two patients have not finished their 45 days follow-up, up to 2 additional incoming patients can be enrolled at the current dose level. In addition, we will give the option of administering 2 additional doses (at the same dose level), 28 days after the first infusion of the same dose, in subjects who have a partial response after one dose or who have received other therapy that may affect the persistence or function of the infused CTL in vivo. If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval.
Dose Levels and Dosing Schedule
Dose Level CTL Dose Given from Day +30 post SCT
- 1x107/m2
- 2.0x107/m2
- 5x107/m2
Escalation of Multi-virus-specific CTL infusions
CMV/AdV/EBV/BKV CTL will be given from day +30 either as prophylaxis or treatment for CMV, EBV, BK and/or adenovirus infection. If the patient has viral reactivation or evidence of CMV/EBV/AdV/BKV disease (e.g. pneumonitis, gastroenteritis and/or retinitis or Post Transplant Lymphoproliferative Disorder (PTLD) or hemorrhagic cystitis the CTL can be given with concurrent antiviral pharmacotherapy.
A dose escalation scheme utilizing cohorts of two patients will be used
Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm described in Section 9 will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual.
The Optimal Dose of Infused CMV/AdV/EBV/BKV-Specific CTL
After all patients in the trial have been evaluated, the optimal dose of infused CMV/AdV/EBV-specific CTL will be determined by the algorithm using the sequentially adaptive EffTox trade-off-based design of Thall et al.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CMV/AdV /EBV/BKV specific T cells | Experimental | Biological: CMV/AdV /EBV/BKV specific T cellsCMV/AdV /EBV/BKV specific T cells will be thawed and transferred to a syringe given by slow intravenous injection over 1-2 minutes. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Pediatric and adult patients (there are no lower and upper age limits for patients) with malignant or nonmalignant diseases who are candidates for transplant.
- Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit selected for CTL expansion must be either:
- Recipients of at least one unmanipulated cord blood unit as described above (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral/BKV and/or EBV infection or reactivation.
- Lansky/Karnofsky scores ≥60
- Absolute neutrophil count (ANC) greater than 500/u
Key exclusion criteria (12 listed)
- Pregnant or lactating
- Patients with active central nervous system disease
- Patients with Karnofsky performance status <70%
- Patients with grade 3 or 4 or primary myelofibrosis
- Patients with suitable related donors Exclusion Criteria at the Time of CTL Infusion
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/AdV /EBV/BKV specific T cellsEach cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm of sequentially adaptive EffTox trade-off-based design of Thall et al will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual. | Biological | CMV/AdV /EBV/BKV specific T cells |
Primary outcome
Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03
Time frame: 45 days for toxicity
The study will determine the optimal dose of intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, Adenovirus and BK virus( BKV) given to patients with or at risk for CMV, EBV, BK virus and adenovirus infection after cord blood transplant. The safety will be assessed by investigational product-related adverse events as per CTCAE v4.03.
1 secondary outcome
Impact of CMV/AdV /EBV/BKV specific T cells will be measured by existence of cells in the system.
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites 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 CMV/AdV /EBV/BKV specific T cells in people with Viral Infection, run by Catherine Bollard 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 14 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2026. 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 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?
This study is still under way. Results are not available in the source record yet.
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?
Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03 (time frame: 45 days for toxicity). 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 14 Aug 2026.