A Study of iMSC for the Prevention of Acute Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

A Prospective, Randomized Controlled Study of Human Induced Pluripotent Stem Cell-derived Mesenchymal Stromal Cells (iMSC) for the Prevention of Acute Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

An open-label, randomized, controlled clinical trial to explore the efficacy and safety of iMSC in preventing the development of acute graft-versus-host disease of degree III-IV in patients after allogeneic hematopoietic stem cell transplantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Graft-versus-Host Disease
• Intervention / Treatment: Combination product: conventional aGVHD prophylaxis; Biological: iMSC

Detailed Description

This is an open-label, randomized, controlled study, enrolled subjects(patients at risk for aGVHD of degree III-IV after allogeneic hematopoietic stem cell transplantation) will be 1:1 randomized to experimental group or control group. Control group will receive conventional aGVHD prophylaxis and the experimental group will receive iMSC injection plus conventional aGVHD prophylaxis, with 28 cases in each group, for a total of 56 subjects.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xiaoxia Hu, MD; Phone Number: +86 021-64370045; Email: hu_xiaoxia@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with malignant or nonmalignant hematologic diseases 7-21 days after allogeneic hematopoietic stem cell transplantation;
• No gender restrictions and age between 14-70 years old；
• Patients received aGVHD prophylaxis regimen of a calcium-modulated phosphatase inhibitor combined with mycophenolate mofetil wtih or without short-course methotrexate and rabbit anti-human thymocyte globulin (CNI+MMF± short-course MTX +ATG)；
• Patients had a MAGIC algorithm probability (MAP) score ≥ 0.14 at +7d or +14d after allogeneic hematopoietic stem cell transplantation(HSCT) (if patients had a MAP< 0.14 at +7d, another test was performed at +14d)；
• Estimated survival≥ 24 weeks；
• Eastern Cooperative Oncology Group（ECOG）≤ 2 points and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI)≤ 3 points；
• Subjects were be treated within 5 days after enrollment；
• Informed consent and willingness to participate in the study.

Exclusion Criteria:

• Serious organ dysfunction such as organ failure after allogeneic HSCT;
• Received more than once HSCT (including autologous transplants);
• Positive for Hepatitis B Surface Antigen (HBsAg) or Hepatitis B Core Antibody (HBcAb) and have Hepatitis B Virus (HBV) DNA titers above the normal range ; positive for Hepatitis C Virus (HCV) antibodies and have positive peripheral blood HCV RNA; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for syphilis;
• Subjects with severe hepatic veno-occlusive disease or sinus veno-occlusive syndrome;
• Primary malignant hematologic disease was not remission;
• Within 6 months prior to enrollment, subjects had other diseases or their physiological conditions may interfere the study results, or had life-threatening complications;
• Those who are suffering mental or neurological illnesses, unable to express will correctly;
• Those with active malignant solid tumors within 5 years prior to participation in this study, with the exception of radically treated cervical cancer, in situ limited prostate cancer, and nonmelanoma skin cancer;
• Subjects known to be potentially allergic or highly sensitized to the cell therapy in the study protocol;
• Have participated or are participating in another clinical trial within one month prior to enrollment;
• Those who are judged by the investigator to be unsuitable for participation in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; conventional aGVHD prophylaxis	Combination product: conventional aGVHD prophylaxis; Cyclosporine or tacrolimus(CNI)+Mycophenolate mofetil(MMF)± Short Course Methotrexate(MTX)+Anti-human T-lymphocyte Globulin（ATG）
Experimental: Trial group; conventional aGVHD prophylaxis + iMSC	Combination product: conventional aGVHD prophylaxis; Cyclosporine or tacrolimus(CNI)+Mycophenolate mofetil(MMF)± Short Course Methotrexate(MTX)+Anti-human T-lymphocyte Globulin（ATG）; Biological: iMSC; 1× 10^6/kg each time, twice a week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of degree III-IV aGvHD	Cumulative incidence of degree III-IV aGvHD at 100 days Within 100 days of first dose	Within 100 days of first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Recurrence Rate (CIR)	Cumulative Recurrence Rate (CIR) at Day 100, Month 6, Month 9, Month 12 , Month 18 , Month 24 after first dose	Day 100, Month 6, Month 9, Month 12 , Month 18 , Month 24 after first dose
Disease-free survival (DFS)	DFS at Day 100, Month 6, Month 9, Month 12 , Month 18 , Month 24 after first dose	Day 100, Month 6, Month 9, Month 12 , Month 18 , Month 24 after first dose
Adverse Event(AE) or Serious Adverse Event(SAE)	Number of participants with treatment-related adverse events or serious adverse events as assessed by CTCAE v5.0	Day 100 after initial infusion

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Xiaoxia Hu, MD, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: April 21, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: prophylaxis; allogeneic hematopoietic stem cell transplantation; iMSC; III-IV aGVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: RJ-BMT-GvHD-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No