Treatment of Refractory cGVHD by Donor-derived Treg Cell Injection Combined With Recombinant Human Interleukin-2

NCT06920199 | Recruiting Early Phase 1

• 1 other identifier: SHSYXY-Treg-cGVHD-2024
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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 refractory cGVHD，and to preliminarily observe the efficacy of the study drugs in subjects with refractory cGVHD.

Conditions

cGVHD

Keywords

Steroid dependence; Refractory cGVHD

Outcome Measures

Primary Outcomes (2)

• 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: 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.

  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.

  Through study completion, an average of 2 year

Secondary Outcomes (11)

• Evaluate the number of Treg cells in subjects' peripheral blood

  An average of 1 year

• Analysis of the number changes of lymphocyte subsets in peripheral blood.

  Through study completion, an average of 2 year

• Score changes in the 36-Item Short Form Health Survey (SF-36)

  Through study completion, an average of 2 year

• Score changes in Lee Chronic Graft-versus-Host Disease Symptom Scale

  Through study completion, an average of 2 year

• Changes in cGVHD severity

  Through study completion, an average of 2 year

Study Arms (1)

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.

Biological: Donor-derived Treg cell injection combined with interleukin 2

Interventions

Donor-derived Treg cell injection combined with interleukin 2 BIOLOGICAL

Subjects received Treg cell infusion at day D0, and interleukin 2 was administered subcutaneously daily from 1 week before to 12 weeks after infusion.

Donor-derived Treg cell injection combined with interleukin 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai General Hospital

Shanghai, 200080, China

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• xianmin song, Doctor

  Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xianmin song, Doctor

CONTACT

18616705298; shongxm@139.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: single-arm, open-label, dose-escalation clinical trial

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: April 9, 2025
• Study Start: June 14, 2025
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): September 15, 2027
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)