Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy

NCT04629833 | Recruiting Phase 3 DMC

• 1 other identifier: MC-MSC.1/aGvHD
• Study Type: interventional
• Target: 210
• Locations: 5 countries
• Sites: 42

Brief Summary

The primary purpose of this trial is to demonstrate the superiority of MC0518 compared to the first used best available therapy (BAT) with respect to overall response rate (ORR) at Day 28 and/or overall survival (OS) until Visit Month 24 in adult and adolescent subjects with steroid-refractory acute graft-versus-host disease (SR-aGvHD).

Conditions

Steroid-refractory Acute Graft-versus-host Disease

Outcome Measures

Primary Outcomes (2)

• Overall Response (OR)

  OR is defined as complete response (CR) or partial response (PR) at Day 28 relative to aGvHD status at baseline. CR is defined as resolution of aGvHD in all involved organs. PR is defined as improvement in 1 stage in 1 or more organs involved with aGvHD symptoms without progression in others. Number of participants with OR will be reported.

  Day 28

• Overall Survival

  Overall survival is defined as the time from randomization to the date of death due to any cause.

  Up to Month 24

Secondary Outcomes (21)

• Freedom from Treatment Failure (FFTF)

  Up to 6 months

• Acute Graft-versus-host Disease (aGvHD) Response

  Days 28, 60, 100 and 180

• Change from Baseline in aGvHD Grades

  Baseline and Days 8, 15, 22, 28, 60, 100 and 180

• Time to Response

  Up to Month 24

• Duration of Response

  Up to Month 24

Study Arms (2)

MC0518

EXPERIMENTAL

Participants will receive MC0518 1-2 million cells/ kilogram infusions (based on body weight at the Screening Visit) once a week for 4 weeks (Visit Day 1, 8, 15, and 22). Participants with partial response (PR) on Day 28 will have 2 additional MC0518 infusions administered on Day 29 and 36.

Biological: MC0518

Best Available Therapy (BAT)

ACTIVE COMPARATOR

Participants will receive any one of the following systemic BATs based on the Investigator's decision: mycophenolate mofetil (MMF), extracorporeal photopheresis (ECP), anti-thymocyte globulin (ATG), everolimus, and ruxolitinib (RUX).

Biological: BAT

Interventions

MC0518 BIOLOGICAL

MC0518 will be intravenously infused immediately after thawing.

MC0518

BAT BIOLOGICAL

BAT including MMF, ECP, ATG, everolimus, and RUX will be administered based on Investigator's decision.

Best Available Therapy (BAT)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant had a previous allogeneic HSCT as indicated for non-malignant (including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies, and bone marrow failure syndromes) or haematological malignant disease, irrespective of human leukocyte antigen match
• Participant has been clinically diagnosed with Grade II to IV aGvHD at the Screening Visit
• Participant has experienced failure of previous first-line aGvHD treatment (ie, SR-aGvHD), defined as: a) aGvHD progression within 3 to 5 days of therapy onset with \>= 2 mg/kg/day of prednisone equivalent or b) failure to improve within 5 to 7 days of treatment initiation with \>= 2 mg/kg/day of prednisone equivalent or c) incomplete response after \> 28 days of immunosuppressive treatment including at least 5 days with \>= 2 mg/kg/day of prednisone equivalent
• Participant has an estimated life expectancy \> 28 days at the Screening Visit
• Male or female participant who is \>= 12 years of age at the Screening Visit

You may not qualify if:

• Participant has overt relapse or progression or persistence of the underlying disease at the Screening Visit
• Participant has received the last HSCT for a solid tumour disease
• Participant has GvHD overlap syndrome at the Screening Visit
• Participant has received systemic first line treatment for aGvHD other than steroids and a prophylaxis with other than calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, anti-thymocyte globulin (ATG), mycophenolate mofetil (MMF), methotrexate (MTX), and / or cyclophosphamide before the Screening Visit
• Participant has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit
• Participant has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit (compliance to be confirmed for the period between the Screening Visit and the Baseline Visit at the Baseline Visit).

Sponsors & Collaborators

• medac GmbH: lead

Study Sites (42)

Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud

Amiens, 80054, France

RECRUITING

CHU Jean Minjoz

Besançon, 25030, France

RECRUITING

Hopital Michallon

Grenoble, 38700, France

RECRUITING

CHRU Lille- Hopital Claude Huriez

Lille, 59000, France

RECRUITING

CHU de Nantes - Hotel Dieu

Nantes, 44093, France

RECRUITING

CHU de Nice Hopital Archet 1

Nice, 06200, France

RECRUITING

Centre Hospitalier Lyon Sud Pavillon Marcel Berard 1G

Pierre-Bénite, 69630, France

RECRUITING

Centre Hospitalier Universitaire CHU de Toulouse

Toulouse, 31059, France

RECRUITING

Hopitaux De Brabois

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

Klinikum rechts der Isar

Munich, Bavaria, 81675, Germany

RECRUITING

Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II - Zentrum fuer Allogene Blutstammzelltransplantation

Würzburg, Bavaria, 97080, Germany

RECRUITING

Klinikum der Johann Wolfgang Goethe-Universitaet - Frankfurt am Main

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

RECRUITING

Uniklinik Koeln

Cologne, North Rhine-Westphalia, 50937, Germany

ACTIVE NOT RECRUITING

Universitaetsklinikum Essen - Klinik fuer Knochenmarktransplantation (KMT)

Essen, North Rhine-Westphalia, 45147, Germany

RECRUITING

Universitaetsklinikum Muenster

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

Universitaetsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, 01307, Germany

RECRUITING

Universitaetsklinikum Leipzig, Selbststaendige Abteilung fur Haematologie und Internistische Onkologie

Leipzig, Saxony, 04103, Germany

RECRUITING

Universitaetsklinikum Jena Klinik fuer Innere Medizin II, Haematologie und Onkologie

Jena, Thuringia, 07740, Germany

RECRUITING

Universitaetsklinikum Jena - Klinik fuer Paediatrische Haematologie und Onkologie

Jena, Thuringia, 07747, Germany

TERMINATED

Charite Universitaetsmedizin

Berlin, 13353, Germany

WITHDRAWN

Helios Klinikum Berlin-Buch

Berlin, 287706, Germany

RECRUITING

University Hospital Bonn, Medizinische Klinik III

Bonn, 53127, Germany

RECRUITING

Universitaetsklinikum Essen - Klinik fuer Paediatrische Haematologie und Onkologie

Essen, 45147, Germany

TERMINATED

Klinikum der Johann Wolfgang Goethe University - University - Klinik fuer Paediatrische Haematologie und Onkologie

Frankfurt, 60590, Germany

RECRUITING

Universitaetsklinikum Freiburg - Zentrum fuer Kinder- und Jugendmedizin (ZKJ) - Klinik fuer Paediatrische Haematologie und Onkologie

Freiburg im Breisgau, 151595, Germany

TERMINATED

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

Universitatsklinikum

Kiel, 24105, Germany

RECRUITING

University Medical Center Mainz

Mainz, 55131, Germany

RECRUITING

Universitaetsklinikum Mannheim

Mannheim, 68167, Germany

RECRUITING

University Hospital Tuebingen Medical Center

Tübingen, 72076, Germany

RECRUITING

Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

TERMINATED

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie, Paastwowy Instytut Badawczy

Gliwice, 44-102, Poland

RECRUITING

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

RECRUITING

Hospital Universitario Vall dHebron

Barcelona, 08035, Spain

RECRUITING

Institut Catal dOncologia

Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Puerta De Hierro

Madrid, 28222, Spain

RECRUITING

Hospital Universitario Carlos Haya

Málaga, 29010, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitari i politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Center for Allogeneic Stem Cell Transplantation and Cell Therapy (CAST), Karolinska Universitetssjukhuset Huddinge

Huddinge, 126464, Sweden

TERMINATED

Study Officials

• Ann-Kristin Möller

  medac GmbH

  STUDY DIRECTOR

Central Study Contacts

Clinical Trial Information

CONTACT

+49 40103 8006-0; ClinicalTrialInformation@medac.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 16, 2020
• Study Start: August 16, 2021
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2030
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DE (22); ES (8); FR (9); PL (2)