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

NCT05531266 | Unknown

• 1 other identifier: 20220831
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

aGVHD

Keywords

aGVHD; Umbilical Cord Mesenchymal Stem Cell

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Cumulative relapse incidence

  180 days

• cumulative incidence of chronic GVHD at one year

  180 days

• Cumulative Incidence of Infectious Complications

  180 days

• Cumulative Incidence of lymphoproliferative disease

  180 days

Study Arms (2)

hUC-MSCs combined with glucocorticoids group.

EXPERIMENTAL

91 patients will be involved in this group

Other: hUC-MSCs

glucocorticoids group

ACTIVE COMPARATOR

91 patients will be involved in this group

Other: glucocorticoids

Interventions

hUC-MSCs OTHER

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.

hUC-MSCs combined with glucocorticoids group.

glucocorticoids OTHER

Participants were treated with glucocorticoids only.

glucocorticoids group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300041, China

RECRUITING

MeSH Terms

Interventions

Glucocorticoids

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Erlie Jiang

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aiming Pang

CONTACT

+86-13820398091; pangaiming@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 7, 2022
• Study Start: September 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2025
• Last Updated: September 7, 2022

Record last verified: 2022-08

Locations

CN (1)