MSC for Treatment of cGVHD After Allo-HSCT

Mesenchymal Stem Cell for Treatment of Chronic Graft-versus-host Disease After Allogenetic Hematopoietic Stem Cell Transplantation

The purpose of this study is to evaluate the efficacy of mesenchymal stem cells in patients with chronic graft-versus-host disease.

Study Overview

• Status: Recruiting
• Conditions: Chronic Graft-versus-host Disease
• Intervention / Treatment: Biological: Mesenchymal stem cells; Drug: Glucocorticoids; Drug: cyclosporine

Detailed Description

Allogeneic hematopoietic stem cell transplantation(allo-HSCT) can cure many hematologic diseases. Although great progress has been made in the prevention and treatment of side effects associated with transplantation,chronic graft-versus-host disease(cGVHD) remains an important complication that occurs in about 50% patients. The mortality of cGVHD and its complication could reach up to 50%,and cGVHD seriously influence the quality of life. At present, the first line treatment of cGVHD remains in discussion.

Mesenchymal stem cells (MSCs) are a form of multipotent adult stem cells that can be isolated from bone marrow (BM), adipose tissue, and cord blood. Clinical applications of human MSCs are evolving rapidly with goals of improving hematopoietic engraftment, preventing and treating GVHD after allo-HSCT and so on. However, the efficacy of treatment of cGVHD remains undetermined.

In the present study, the investigators will prospectively evaluate the efficacy and safety of ex-vivo-expanded MSCs in treating patients with cGVHD.

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A patient age of 18-65 years
• Recipients of allogeneic hematopoietic stem cell transplantation Patients with moderate/ severe cGVHD without systemic treatment
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Primary disease relapse
• Expected lifetime less than 3 months
• Patients with any conditions not suitable for the trial (investigators' decision)

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: MSCs group; MSCs group refers to treatment with mesenchymal stem cells (1×10^6 cells/kg, intravenously) weekly for 8 doses. Besides, glucocorticoids and cyclosporine (CsA) will be used for treatment concurrently.	Biological: Mesenchymal stem cells; Mesenchymal stem cells (MSCs) will be intravenously infused via a central venous catheter(at a dose of 1×10^6 cells/kg, over 15 mins) weekly. MSCs will be administrated for 8 doses.; Drug: Glucocorticoids; Glucocorticoids (i.e. Methylprednisolone) will be used with an initial dose of 1mg/kg.; Drug: cyclosporine; Cyclosporine (CsA) will be used with an initial dose of 2.5mg/kg/d and adjusted according to the concentration of CsA. The targeted concentration is 200-300 ng/Ml.
Active Comparator: Control group; Glucocorticoids and CsA will be used for treatment.	Drug: Glucocorticoids; Glucocorticoids (i.e. Methylprednisolone) will be used with an initial dose of 1mg/kg.; Drug: cyclosporine; Cyclosporine (CsA) will be used with an initial dose of 2.5mg/kg/d and adjusted according to the concentration of CsA. The targeted concentration is 200-300 ng/Ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall response rate （ORR）includes complete response (CR) and part response (PR).	12 weeks after the first dose of MSCs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS)	1 year after the first dose of MSCs
DFS	Disease-free survival (DFS)	1 year after the first dose of MSCs
Response rate		4 weeks after the first dose of MSCs
EBV DNA-emia	EBV DNA-emia refers to detection of EBV DNA in peripheral blood via PCR.	1 year after the first dose of MSCs
CMV DNA-emia	CMV DNA-emia refers to detection of CMV DNA in peripheral blood via PCR.	1 year after the first dose of MSCs
PGF	Poor graft function (PGF) refers to a slow or incomplete recovery of blood cell counts (ANC ≤0.5x10^9/L and PLT ≤20x10^9/L) by +28 days after allo-HSCT or a fall in blood cell counts to levels fulfilling the diagnostic criteria for PGF after successful and prompt hematopoietic engraftment.	1 year after the first dose of MSCs

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Peking University People's Hospital; Sun Yat-sen University; Xinqiao Hospital, Army Medical University
• Investigators: Principal Investigator: Qi-fa Liu, MD, Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 10, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: December 26, 2020
• First Submitted That Met QC Criteria: December 29, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Actual): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 29, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; Hematopoietic Stem Cell Transplantation; Chronic Graft-versus-host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Glucocorticoids
• Other Study ID Numbers: MSC-cGVHD-2020

Drug and device information, study documents

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