cGVHDEarly Phase 1NCT06920199
Treatment of Refractory cGVHD by Donor-derived Treg Cell Injection Combined With Recombinant Human Interleukin-2
A Early Phase 1 study testing Donor-derived Treg cell injection combined with interleukin 2 in people with cGVHD, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
This study is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, tolerability, changes and persistence of peripheral blood Treg cells, and pharmacodynamic characteristics of donor-derived Treg cell injection combined with recombinant human interleukin-2 in treating subjects with… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- cGVHD
- What is being tested?
- Donor-derived Treg cell injection combined with interleukin 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 14 Jun 2025to 15 Sep 2027
- Phase
- Early 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects aged 18-70 years old, male or female;
- The subjects had received allo-HSCT, including cord blood transplantation;
- TSubjects with moderate/severe cGVHD that meets the NIH diagnostic criteria (031) for steroid dependence or resistance, meeting one of the following:
- There was no improvement in cGVHD in initial treatment patients treated with > 0.5mg/kg/ day or 1 mg/kg/ day every other day for at least 4 weeks;
- Steroid dependence: predtisone dose > 0.25 mg/kg/d or > 0.5 mg/kg/qod cGVHD relapse or progression; cGVHD recurred after two attempts to gradually reduce prednisone dose at an interval of at least 8 weeks, with prednisone dose > 0.25 mg/kg/day to be maintained.
- Prednisone dose > 0.25 mg/kg/d for more than 4 weeks; Subjects must maintain a stable prednisone dose for 4 weeks prior to the first Treg cell infusion and not increase or discontinue other immunosuppressants (including cyclosporine, tacrolimus, and sirolimus);
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- The ECOG score of the subjects was 0-2;
- the expected survival of the subject is more than 3 months;
- Liver, kidney, heart and lung function meet the following requirements (except liver and kidney dysfunction caused by cGVHD) :
- Creatinine clearance (calculated by Cockcroft Gault formula) ≥60 mL/min;
- Cardiac ejection fraction greater than 50%, no clinically significant electrocardiogram changes;
- Forced expiratory volume (FEV1) in the first second of baseline lung function ≥50%, and FEV1 decline caused by cGVHD could be included;
- Total bilirubin ≤2.0ULN; ALT and AST≤3ULN, ALT and AST increases caused by cGVHD could be included in the group.
- Hematopoietic function: neutrophils >1×10^9/L, platelets >25×10^9/L; Supportive treatments such as platelet transfusion and other cytokines are excluded.
- The subject or the subject's guardian can understand this experiment and has signed the informed consent.
- Donor age 14-70 years old, male or female;
- The ECOG score of the donor is 0-1;
- The donor must be a hematopoietic stem cell donor who underwent allo-HSCT prior to the subject;
- Female donors must test negative for serum or urine beta-human chorionic gonadotropin (HCG) within 3 weeks of blood collection;
- The donor can establish the necessary venous access for collection, without the contraindication of white blood cell collection; If peripheral venous leukocyte collection is insufficient, be willing to insert a central catheter; (15) The donor agrees to donate and signs a consent form.
Who cannot join
- Subjects had a recurrence of primary malignant disease before receiving Treg treatment;
- The subjects had persistent, recurrent or delayed aGVHD;
- Continuous use of prednisone >1 mg/kg/day is required;
- The severity of the subject's cGVHD cannot be assessed by physical examination or laboratory examination;
- overlap syndrome；
- The subjects had major organ (cardio-cerebrovascular, pulmonary) dysfunction not caused by cGVHD, and had previous (within 3 months) gastrointestinal active bleeding; History of uncontrolled hypertension or hypertensive crisis or hypertensive encephalopathy, history or evidence of significant cardiovascular and cerebrovascular risk, including any of the following conditions: congestive heart failure, unstable angina pectoris, clinically significant arrhythmias (e.g., ventricular fibrillation, ventricular tachycardia, etc.); History of arterial thrombosis (such as stroke, transient ischemic attack) within the last 3 months; A history of symptomatic deep vein thrombosis, pulmonary embolism, or coronary angiogenesis, defibrillation, or any clinically relevant complication or disease within the last 6 months that could pose a risk to subject safety or interfere with study evaluation, procedure, or completion;
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- The subjects are hemodialysis patients;
- The subject or donor has an active, uncontrolled bacterial, viral, or fungal infection that requires treatment；
- The subjects are pregnant or lactating women; Subjects who plan to become pregnant during the post-transfusion study, or within 1 year of completion or withdrawal from the study;
- Participants who had received IL-2 therapy or drug therapy targeting IL-2 within 4 weeks prior to enrollment；
- Received DLI treatment within 100 days before enrollment;
- Received CAR-T or similar engineered cell therapy within 100 days prior to enrollment;
- Had received new cGVHD therapies (including imatinib, BTK inhibitors, rituximab and other immunosuppressants) within 4 weeks before enrollment after transplantation;
- Have a history of microvascular diseases such as TMA, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, etc；
- Subjects with poor IL-2 treatment compliance;
- Participants who participated in other CGVHD-related clinical studies within 4 weeks prior to enrollment;
- Subjects who are known to be allergic to any component of Treg cell injection;
- Any situation that the investigator believes would compromise the safety of the subject or interfere with the study purpose, or that the investigator considers it inappropriate to participate in the study;
- Having a medical condition that affects the signing of written informed consent or the inability to follow study procedures; Unwilling or unable to comply with research requirements;
- The donor was a pregnant woman.
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
Shanghai General Hospital
Shanghai, 200080
xianmin song, Doctor, 18616705298, shongxm@139.com
About this study
Official title: Clinical Study to Evaluate the Safety and Efficacy of Donor-derived Treg Cell Injection Combined With Recombinant Human Interleukin-2 in the Treatment of Refractory cGVHD Subjects
This study is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, tolerability, changes and persistence of peripheral blood Treg cells, and pharmacodynamic characteristics of donor-derived Treg cell injection combined with recombinant human interleukin-2 in treating subjects with refractory cGVHD，and to preliminarily observe the efficacy of the study drugs in subjects with refractory cGVHD.
Read the detailed description
This study is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, tolerability, changes and persistence of peripheral blood Treg cells, and pharmacodynamic characteristics of donor-derived Treg cell injection combined with recombinant human interleukin-2 in treating subjects with refractory cGVHD，and to preliminarily observe the efficacy of the study drugs in subjects with refractory cGVHD.In this study, rapid titration of the first dose group and a "3+3" rule design were used for dose escalation to minimize patient exposure to ineffective doses while minimizing the occurrence of risk.Three dose groups were set up: 1×10^6 Treg cells /kg dose group, 5.0×10^6 Treg cells /kg dose group and 10×10^6Treg cells /kg dose group.One infusion per dose group.
- Conditions
- cGVHD
- Being tested
- Donor-derived Treg cell injection combined with interleukin 2
- Keywords
- Steroid dependence, Refractory cGVHD
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor-derived Treg cell injection combined with interleukin 2Biological
Subjects received Treg cell infusion at day D0, and interleukin 2 was administered subcutaneously daily from 1 week before to 12 weeks after infusion.
| Study group | Role | What they receive |
|---|---|---|
| Donor-derived Treg cell injection combined with interleukin 2 | Experimental | Donor-derived Treg cell injection, injections, The first dose was 1.0× 10^6Treg cells /kg, the second dose was 5.0×10^6Treg cells /kg, and the third dose was 10.0×10^6Treg cells /kg,single-dose.
Interleukin 2,1 million IU/m2/d,last 13 weeks. Receives: Biological: Donor-derived Treg cell injection combined with interleukin 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection。
DLT is defined as any of the following conditions related to the study drug within 28 days after the subject's infusion of Treg cell injection, despite treatment:
- Grade 4 or 5 cytokine release syndrome caused by Treg cell injection treatment;
- Grade 3 cytokine syndrome caused by Treg cell injection treatment and no remission to grade 2 or below within 7 days;
- Occurrence of grade 3 or higher neurotoxicity;
- Grade 4 hematologic toxicity: caused by non-underlying disease and lasting ≥ 28 days (except for lymphopenia, neutrophil and thrombocytopenia caused by chemotherapy pretreatment);
- Any unanticipated toxicity that necessitates discontinuation of treatment at the discretion of the investigator or collaborating unit.
Measured: Up to day 28
Incidence of grade 3 and above adverse reactions
Incidence of adverse events associated with the study products；Adverse events assessed according to NCI-CTCAE v5.0.
Measured: Through study completion, an average of 2 year
Secondary outcomes (11)
Evaluate the number of Treg cells in subjects' peripheral blood
Evaluate the number of Treg cells in subjects' peripheral blood after donor-derived Treg cell injection administration
Measured: An average of 1 year
Analysis of the number changes of lymphocyte subsets in peripheral blood.
Analysis of the number changes of lymphocyte subsets in peripheral blood, Including T/B/NK cells.
Measured: Through study completion, an average of 2 year
Score changes in the 36-Item Short Form Health Survey (SF-36)
Adopt 36-Item Short Form Survey (SF-36)to analyze the changes in patients' scores after medication compared with baseline.
Measured: Through study completion, an average of 2 year
Score changes in Lee Chronic Graft-versus-Host Disease Symptom Scale
Adopt 36-Item Short Form Survey (SF-36)to analyze the changes in patients' scores after medication compared with baseline.
Measured: Through study completion, an average of 2 year
Changes in cGVHD severity
Changes in cGVHD severity,according to chronic graft-versus-host disease grading system.
Measured: Through study completion, an average of 2 year
Objective Response Rate (ORR)
To evaluate the efficacy of donor-derived Treg cells combined with low-dose IL-2 in the treatment of refractory cGVHD subjects, including 12 and 24 weeks of ORR.
Measured: Through study completion, an average of 2 year
Patient-reported Outcomes
Reports directly from patients on their own health, functional status, and treatment experience, excluding explanations from health care workers or anyone else. A score of ≥7 on the Lee cGVHD Symptom Scale was associated with improved quality of life.
Measured: Through study completion, an average of 2 year
Proportion of subjects able to reduce steroid requirement to <0.25 mg/kg/ day.
Proportion of subjects able to reduce steroid requirement to <0.25 mg/kg/ day.
Measured: Through study completion, an average of 2 year
Duration of response after administration (DOR)
Duration of response after administration (DOR),Defined as the time between first remission and disease progression, new cGvHD systemic treatment, or all-cause death, whichever occurs first.
Measured: Through study completion, an average of 2 year
Failure-free survival after administration (FFS)
Failure-free survival after administration (FFS),The time from the beginning of cell reinfusion to the first disease progression, recurrence after remission, or death from any cause.
Measured: Through study completion, an average of 2 year
Overall survival
The time from cell retransfusion to death from any cause.
Measured: Through study completion, an average of 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2025
- Study start14 Jun 2025
- Primary completion15 May 2027 (estimated)
- Study completion15 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for cGVHDStudies of the same condition, open and under way.
- More trials run by Shanghai General Hospital, Shanghai Jiao Tong University School 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single-arm, open-label, dose-escalation clinical trial
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
- Investigators
- xianmin song, Doctor, Principal investigator, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06920199
- Sponsor's protocol ID
- SHSYXY-Treg-cGVHD-2024
- Status last verified
- Sep 2025
- First submitted
- 19 Mar 2025
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study to Evaluate the Safety and Efficacy of Donor-derived Treg Cell Injection Combined With Recombinant Human Interleukin-2 in the Treatment of Refractory cGVHD Subjects
- ClinicalTrials.gov ID
- NCT06920199
- Acronym / sponsor ID
- SHSYXY-Treg-cGVHD-2024
- Conditions
- cGVHD
- Keywords
- Steroid dependence, Refractory cGVHD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 14 Jun 2025 (actual)
- Primary completion
- 15 May 2027 (estimated)
- Study completion
- 15 Sep 2027 (estimated)
- First posted
- 9 Apr 2025 (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 study is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, tolerability, changes and persistence of peripheral blood Treg cells, and pharmacodynamic characteristics of donor-derived Treg cell injection combined with recombinant human interleukin-2 in treating subjects with refractory cGVHD，and to preliminarily observe the efficacy of the study drugs in subjects with refractory cGVHD.
Detailed description
This study is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, tolerability, changes and persistence of peripheral blood Treg cells, and pharmacodynamic characteristics of donor-derived Treg cell injection combined with recombinant human interleukin-2 in treating subjects with refractory cGVHD，and to preliminarily observe the efficacy of the study drugs in subjects with refractory cGVHD.In this study, rapid titration of the first dose group and a "3+3" rule design were used for dose escalation to minimize patient exposure to ineffective doses while minimizing the occurrence of risk.Three dose groups were set up: 1×10^6 Treg cells /kg dose group, 5.0×10^6 Treg cells /kg dose group and 10×10^6Treg cells /kg dose group.One infusion per dose group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single-arm, open-label, dose-escalation clinical trial
| Arm | Type | Receives |
|---|---|---|
| Donor-derived Treg cell injection combined with interleukin 2 | Experimental | Biological: Donor-derived Treg cell injection combined with interleukin 2Donor-derived Treg cell injection, injections, The first dose was 1.0× 10^6Treg cells /kg, the second dose was 5.0×10^6Treg cells /kg, and the third dose was 10.0×10^6Treg cells /kg,single-dose. Interleukin 2,1 million IU/m2/d,last 13 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Subjects aged 18-70 years old, male or female;
- The subjects had received allo-HSCT, including cord blood transplantation;
- TSubjects with moderate/severe cGVHD that meets the NIH diagnostic criteria (031) for steroid dependence or resistance, meeting one of the following:
- Prednisone dose > 0.25 mg/kg/d for more than 4 weeks; Subjects must maintain a stable prednisone dose for 4 weeks prior to the first Treg cell infusion and not increase or discontinue other immunosuppressants (including cyclosporine, tacrolimus, and sirolimus);
- The ECOG score of the subjects was 0-2;
Key exclusion criteria (20 listed)
- Subjects had a recurrence of primary malignant disease before receiving Treg treatment;
- The subjects had persistent, recurrent or delayed aGVHD;
- Continuous use of prednisone >1 mg/kg/day is required;
- The severity of the subject's cGVHD cannot be assessed by physical examination or laboratory examination;
- overlap syndrome；
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 |
|---|---|---|
| Donor-derived Treg cell injection combined with interleukin 2Subjects received Treg cell infusion at day D0, and interleukin 2 was administered subcutaneously daily from 1 week before to 12 weeks after infusion. | Biological | Donor-derived Treg cell injection combined with interleukin 2 |
Primary outcome
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection
Time frame: Up to day 28
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection。 DLT is defined as any of the following conditions related to the study drug within 28 days after the subject's infusion of Treg cell injection, despite treatment: 1. Grade 4 or 5 cytokine release syndrome caused by Treg cell injection treatment; 2. Grade 3 cytokine syndrome caused by Treg cell injection treatment and no remission to grade 2 or below within 7 days; 3. Occurrence of grade 3 or higher neurotoxicity; 4. Grade 4 hematologic toxicity: caused by non-underlying disease and lasting ≥ 28 days (except for lymphopenia, neutrophil and thrombocytopenia caused by chemotherapy pretreatment); 5. Any unanticipated toxicity that necessitates discontinuation of treatment at the discretion of the investigator or collaborating unit.
Incidence of grade 3 and above adverse reactions
Time frame: Through study completion, an average of 2 year
Incidence of adverse events associated with the study products；Adverse events assessed according to NCI-CTCAE v5.0.
11 secondary outcomes
Evaluate the number of Treg cells in subjects' peripheral blood
Time frame: An average of 1 year
Analysis of the number changes of lymphocyte subsets in peripheral blood.
Time frame: Through study completion, an average of 2 year
Score changes in the 36-Item Short Form Health Survey (SF-36)
Time frame: Through study completion, an average of 2 year
Score changes in Lee Chronic Graft-versus-Host Disease Symptom Scale
Time frame: Through study completion, an average of 2 year
Changes in cGVHD severity
Time frame: Through study completion, an average of 2 year
Objective Response Rate (ORR)
Time frame: Through study completion, an average of 2 year
Patient-reported Outcomes
Time frame: Through study completion, an average of 2 year
Proportion of subjects able to reduce steroid requirement to <0.25 mg/kg/ day.
Time frame: Through study completion, an average of 2 year
Duration of response after administration (DOR)
Time frame: Through study completion, an average of 2 year
Failure-free survival after administration (FFS)
Time frame: Through study completion, an average of 2 year
Overall survival
Time frame: Through study completion, an average of 2 year
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 30 Sep 2025.
- 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.
xianmin song, Doctor principal investigator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Donor-derived Treg cell injection combined with interleukin 2 in people with cGVHD, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine 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 20 inclusion and 20 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 30 Sep 2025. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 xianmin song, Doctor (18616705298, shongxm@139.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection (time frame: Up to day 28). The study lists 2 primary outcomes in all. 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 30 Sep 2025.