EBV-associated Hemophagocytic LymphohistiocytosisPhase 1NCT06135922
Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
A Phase 1 study testing EBV-TCR-T cells in people with EBV-associated Hemophagocytic Lymphohistiocytosis and EBV Infection, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection Read more about this study
- Who is it for?
- Ages 1 year to 60 years
- Conditions the study is for
- EBV-associated Hemophagocytic Lymphohistiocytosis, EBV Infection
- What is being tested?
- EBV-TCR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2023to 31 Dec 2026
- Phase
- Phase 1
- 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 1 year to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 1-60 years, gender unlimited.
- Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
- Fully understood and informed the study and signed the ICF.
- Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
- TCRT-T cell donor inclusion criteria: 1)Age >=8 years, gender unlimited; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.
Who cannot join
- Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
- Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV or left ventricular ejection fraction<50%) one week before TCR-T cell infusion.
- Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
- Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
- Have tumours, active and uncontrolled malignant diseases.
- Serologically positive for HIV-Ab or TAP-ab.
Show all 12Show fewer
- Pregnant or lactating women.
- Men and their partners or women of childbearing potential refused contraception during the study period.
- Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
- Participated in any other clinical study of drugs and medical devices before 4 weeks of enrollment.
- Allergy to albumin.
- TCRT-T cell donor exclusion criteria: 1) pregnant woman; 2) Serologically positive for HBsAg, HCV-Ab, HIV-Ab or TAP-ab; 3) EBV-DNA or CMV-DNA positive; 4) other uncontrolled infection; 5) Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Daihong Liu, Doctor, +86 18301339032, daihongrm@163.com
Liping Dou, Doctor, +8613681207138, lipingruirui@163.com
About this study
Official title: Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection
Read the detailed description
Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and asymptomatic EBV shedders. The inability to control EBV infection can lead to some patients developing EBV-positive B-cell lymphomas, chronic active EBV infections, and hemophagocytic lymphohistiocytosis (HLH). In this prospective study, HLA-A*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 1×10^6/kg to 1×10^8/kg of EBV-TCR-T cells will be infused into patients with EBV-HLH or EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.
- Being tested
- EBV-TCR-T cells
- 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-TCR-T cellsBiological
The patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10^6/kg to 1×10^8/kg EBV-TCR-T cells per dose.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: EBV-TCR-T cells | Experimental | The patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10^6/kg to 1×10^8/kg EBV-TCR-T cells per dose Receives: Biological: EBV-TCR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Percentage of participants with adverse events
Measured: 1 year after EBV-TCR-T treatment
Secondary outcomes (9)
Dose-limiting toxicity (DLT)
Toxic effects considered by the investigators to be related to the EBV-TCR-T
Measured: 28 days after EBV-TCR-T treatment
Maximum tolerated dose （MTD）
The highest dose of DLT was seen in 1/6 of subjects
Measured: 28 days after EBV-TCR-T treatment
The proportion of EBV-DNA negative patients
The proportion of patients EBV-DNA negative after EBV-TCR-T treatment
Measured: 180 days after EBV-TCR-T treatment
The time to EBV-DNA negative
The time from the start of therapy to EBV-DNA negative detected
Measured: 180 days after EBV-TCR-T treatment
Changes of EBV-DNA copies number
Quantitative PCR will be used to determine viral copy numbers in peripheral blood.
Measured: 1 year after EBV-TCR-T treatment
Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells
Cmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Measured: 28 days after EBV-TCR-T treatment
Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells
AUC of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Measured: 28 days after EBV-TCR-T treatment
Time to peak (Tmax) of EBV-TCR-T cells
Tmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Measured: 28 days after EBV-TCR-T treatment
Half life time (T1/2) of EBV-TCR-T cells
T1/2 of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Measured: 28 days after EBV-TCR-T treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start1 Aug 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EBV-associated Hemophagocytic LymphohistiocytosisStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daihong Liu, Chinese PLA General Hospital
- Investigators
- Daihong Liu, Doctor, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06135922
- Sponsor's protocol ID
- S2022-381-01
- Status last verified
- Oct 2023
- First submitted
- 12 Nov 2023
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
- ClinicalTrials.gov ID
- NCT06135922
- Acronym / sponsor ID
- S2022-381-01
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Nov 2023 (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 is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection
Detailed description
Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and asymptomatic EBV shedders. The inability to control EBV infection can lead to some patients developing EBV-positive B-cell lymphomas, chronic active EBV infections, and hemophagocytic lymphohistiocytosis (HLH). In this prospective study, HLA-A*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 1×10^6/kg to 1×10^8/kg of EBV-TCR-T cells will be infused into patients with EBV-HLH or EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: EBV-TCR-T cells | Experimental | Biological: EBV-TCR-T cellsThe patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10^6/kg to 1×10^8/kg EBV-TCR-T cells per dose |
Who may qualify
- Ages
- 1 year to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Age 1-60 years, gender unlimited.
- Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
- Fully understood and informed the study and signed the ICF.
- Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
- TCRT-T cell donor inclusion criteria: 1)Age >=8 years, gender unlimited; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.
Key exclusion criteria (12 listed)
- Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
- Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV or left ventricular ejection fraction<50%) one week before TCR-T cell infusion.
- Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
- Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
- Have tumours, active and uncontrolled malignant diseases.
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-TCR-T cellsThe patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10^6/kg to 1×10^8/kg EBV-TCR-T cells per dose. | Biological | Experimental: EBV-TCR-T cells |
Primary outcome
Adverse events
Time frame: 1 year after EBV-TCR-T treatment
Percentage of participants with adverse events
9 secondary outcomes
Dose-limiting toxicity (DLT)
Time frame: 28 days after EBV-TCR-T treatment
Maximum tolerated dose （MTD）
Time frame: 28 days after EBV-TCR-T treatment
The proportion of EBV-DNA negative patients
Time frame: 180 days after EBV-TCR-T treatment
The time to EBV-DNA negative
Time frame: 180 days after EBV-TCR-T treatment
Changes of EBV-DNA copies number
Time frame: 1 year after EBV-TCR-T treatment
Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells
Time frame: 28 days after EBV-TCR-T treatment
Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells
Time frame: 28 days after EBV-TCR-T treatment
Time to peak (Tmax) of EBV-TCR-T cells
Time frame: 28 days after EBV-TCR-T treatment
Half life time (T1/2) of EBV-TCR-T cells
Time frame: 28 days after EBV-TCR-T treatment
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 18 Nov 2023.
Related trials for EBV-associated Hemophagocytic Lymphohistiocytosis
Active, not recruitingPhase 1
CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene
Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma
Recruiting
Letermovir Prophylaxis in Children With EBV-Positive T/NK-Cell Lymphoproliferative Disease and Refractory/Relapsed EBV-Associated Hemophagocytic Lymphohistiocytosis
EBV-associated T/NK-cell Lymphoproliferative Diseases, Refractory/Relapsed EBV-related Hemophagocytic Lymphohistiocytosis
Not yet recruitingObservational study
Segmental Resection Combined With DEP Regimen for EBV-HLH Patients With Intestinal Involvement
Hemophagocytic Lymphohistiocytosis, Epstein-Barr Virus
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.
Daihong Liu, Doctor principal investigator
Chinese PLA General Hospital
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 EBV-TCR-T cells in people with EBV-associated Hemophagocytic Lymphohistiocytosis and EBV Infection, run by Chinese PLA General Hospital at 1 site in China.
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 5 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: looking for participants now, as of the sponsor's last update on 18 Nov 2023. 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 China. 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?
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?
Contact Daihong Liu, Doctor (+86 18301339032, daihongrm@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 1 year after EBV-TCR-T treatment). 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 18 Nov 2023.