Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease

Clinical Study of Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease

Allogenic haemopoietic stem cell transplantation (allo-HSCT) is the effective treatment for many hematologic malignancies and some non-malignant diseases. In recent years, with the rapid improvement of economy and medical level, the number of cases of hematopoietic stem cell transplantation (HSCT) develops rapidly in China. In 2019, 12,323 cases of HSCT were completed in China, with allo-HSCT accounting for 9600 cases of which.

However, Graft versus host disease (GVHD) is one of the most common and serious complications after Allo-HSCT. The incidence of acute GVHD (aGVHD) is as high as 40%-60% in HLA-matched sibling transplantation, and the incidence is even higher in haplo-hematopoietic stem cell transplantation(haplo-HSCT) and unrelated donor transplantation. By Glucksberg grading standard, the 5-year survival rates of grade III and IV aGVHD are 25% and 5% respectively, indicating severe GVHD directly affects the survival of Allo-HSCT patients.

The first-line treatment for aGVHD is still glucocorticoid, while the effective rate is only 30%-50%. Moreover, due to immunosuppression and increasing risk of infection, the efficacy of second-line treatments including polyclonal antibodies, monoclonal antibodies, immunosuppressants, immunotoxins, chemotherapy drugs, and light therapy for steroid resistant aGVHD is also poor, with the overall survival rate of 5%-30%.

Mesenchymal stem cells (MSCs) are multipotent cells, which can promote engraftment and hematopoietic reconstruction by secreting a variety of hematopoietic promoting factors, expressing adhesion molecules supporting hematopoietic stem cells, guiding homing of hematopoietic stem cells and providing hematopoietic microenvironment. At the same time, MSCs can modulate immune responses by affecting the proliferation of T cells and the migration of T cells and DC, inducing the expansion of Treg cells, inhibiting the secretion of antibodies by B lymphocytes, and regulating the secretion of soluble factors such as NO and IDO. As a result of these characteristics and the poor immunogenicity, MSCs are a promising alternative treatment for GVHD.

Currently, UK and EU guidelines has recommended MSC as a third-line treatment for grade 2-4 acute GVHD, and the safety and efficacy of umbilical cord derived MSCs in the prevention and treatment of GVHD has also been reported by several transplantation centers in China.However, MSCs have not been used for first-line treatment of aGVHD. Therefore, the investigators designed this study to evaluate the safety and efficacy of UC-derived MSCs as the first line treatment in patients with aGVHD.

Study Overview

• Status: Recruiting
• Conditions: aGVHD
• Intervention / Treatment: Other: hUC-MSCs; Other: glucocorticoids

Detailed Description

This prospective, randomized and controlled study is to investigate the efficacy and safety of Umbilical Cord Mesenchymal Stem Cells as First-line Treatment for Patients With Acute Graft Versus Host Disease. Investigators will recruit 182 patients with acute leukemia, with 91 of them entering the hUC-MSCs combined with glucocorticoids group. and receiving hUC-MSCs at a dose of 1×10^6 /kilogram (kg) actual body weight at Screening for twice per week in 1-2 weeks and once a week in 3-4 weeks after being rolled into this study, with the glucocorticoid given at the same time. while the other 91 entering the glucocorticoids group receiving glucocorticoids only. Then primary outcomes including the ORR at day 180 post initiation of therapy, as well the secondary outcomes including cumulative relapse incidence、cumulative incidence of chronic GVHD 、cumulative Incidence of infectious complications and cumulative Incidence of lymphoproliferative disease will be measured during 180 days after the intervention being finished.

• Study Type: Interventional
• Enrollment (Anticipated): 182
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300041
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
      • Principal Investigator: Erlie Jiang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient who has undergone an allogeneic haematopoietic stem cell transplantation (HSCT) and developed acute graft versus host disease (aGVHD)
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
• serum creatinine less than twice the upper limit of normal or creatinine clearance greater 50 ml/min within 28 days.
• Patients had recovered from previous treatments
• Signing written informed consent and agreeing with taking designated umbilical cord blood

Exclusion Criteria:

• Patients had severe allergy history
• Patients with unstable angina or whose cardiac function grading III-IV.
• Patients with chronic respiratory disease requiring continuous oxygen supplement
• Patients with active hepatitis B or active hepatitis C or AIDS infection
• Patients with Uncontrolled viral or bacterial infections
• Patients with severe psychiatric or physical illness that would limit compliance with study requirements
• Patients who received any other investigational study or treatment within 30 days
• Secondary malignancy
• Allergic to blood products
• Other causes which are not suitable for the trial in investigator's consideration

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: hUC-MSCs combined with glucocorticoids group.; 91 patients will be involved in this group	Other: hUC-MSCs; Participants will be treated with hUC-MSCs at a dose of 1×10^6 /kilogram (kg) actual body weight at Screening for twice per week in 1-2 weeks and once a week in 3-4 weeks after being rolled into this study. At the same time, patients will be treated with glucocorticoids according to patients' condition.
Active Comparator: glucocorticoids group; 91 patients will be involved in this group	Other: glucocorticoids; Participants were treated with glucocorticoids only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy	ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) according to aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative relapse incidence	Defined as the cumulative incidence of relapse after the day of transplantation.	180 days
cumulative incidence of chronic GVHD at one year	chronic graft versus host disease will be diagnosed and graded by National Institute of Health Consensus (NIH Consensus).	180 days
Cumulative Incidence of Infectious Complications	Defined as cumulative incidence of viral, fungal and bacterial infections.	180 days
Cumulative Incidence of lymphoproliferative disease	Defined as the cumulative incidence of lymphoproliferative disease after the day of transplantation.	180 days

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: aGVHD; Umbilical Cord Mesenchymal Stem Cell
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: 20220831

Drug and device information, study documents

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