Efficacy and Safety of UC-MSCs for the Treatment of Steroid-resistant aGVHD Following Allo-HSCT

Efficacy and Safety of UC-MSCS for the Treatment of Steroid-resistant aGVHD Following Allo-HSCT: A Multicenter, Randomized, Open-label Trial

Randomized, open-label, multicenter study to investigate the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSC) for the treatment of steroid-resistant acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a view to establishing an effective treatment protocol for steroid-resistant aGVHD.

Study Overview

• Status: Completed
• Conditions: Graft Vs Host Disease
• Intervention / Treatment: Drug: UC-MSC; Drug: Anti-CD25 mAb

Detailed Description

A total of 130 patients with steroid-resistant aGVHD after allo-HSCT are enrolled in this multicenter, randomized, controlled trial. Patients were randomized to UC-MSC + anti-CD25 monoclonal antibodies (mAb) group and anti-CD25 mAb group. The complete response (CR) rate after 4 weeks of treatment in the two groups will be compared. Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Peking University Insititute of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Confirmed diagnosed steroid-resistant aGVHD after allo-HSCT. 2. Neutrophile granulocyte (ANC) ≥ 0.5 x 10^9/L. 3. Creatinine below 2 times normal upper limit . 4. Willing and able to sign written informed consent.

Exclusion Criteria:

- 1. Untoleratation of the treatment. 2. Primary disease are not effectively controlled or are progressing. 3. Active infection (Bacteria, fungi, viruses ). 4. Combined with dysfunction of multiple organ. 5. Female patients who are nursing or pregnant, or who contemplate pregnancy during the study period.

6. Patients who are deemed unsuitable for the study by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UC-MSC and anti-CD25 mAb; UC-MSC, iv, 1×10^6 cells/kg, once a week, for 4 weeks. Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, 4 weeks. Other treatment would replace it according to clinical experience if aGVHD continue to progress within 3 weeks of treatment or patients are lack of response after 4 weeks of treatment. The treatment would be repeated in another 4 weeks if patients receive partial response after the first 4 weeks of treatment.	Drug: UC-MSC; UC-MSC, iv, 1×10^6 cells/kg, once a week, for 4 weeks.; Other Names: Umbilical cord-derived mesenchymal stem cells; Drug: Anti-CD25 mAb; Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, for 4 weeks.; Other Names: Basiliximab
Active Comparator: Anti-CD25 mAb; Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, for 4 weeks. Other treatment would replace it according to clinical experience if aGVHD continue to progress within 3 weeks of treatment or patients are lack of response after 4 weeks of treatment. The treatment would be repeated in another 4 weeks if patients receive partial response after first 4 weeks of treatment.	Drug: Anti-CD25 mAb; Anti-CD25 mAb, iv, 20mg，twice in first week and once a week thereafter, for 4 weeks.; Other Names: Basiliximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete remission	Complete remission of aGVHD related symptoms and indicators	4 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time from randomization to death for any reason ( the last follow-up time for missing patients; end date of follow-up for patients who are live at the end of the study).	At the end of Week 4 / 8 / 12 / 24 / 52.
Rate of partial remission	improvement of aGVHD staging in one or more organs without progression in other organs	4 weeks after treatment
Infusion toxicity	Acute toxicity responses include impaired function of heart, kidney and liver	From the beginning of to four hours after every infusion of UC-MSC

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Sun Yat-sen University; Third Military Medical University; Southern Medical University, China
• Investigators: Principal Investigator: Xiaohui Zhang, doctor, Peking University People's Hospital, Peking University Insititute of Hematology

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): May 30, 2022
• Study Completion (Actual): May 2, 2023

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Basiliximab
• Other Study ID Numbers: GVHD-PKU2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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