Clinical trial NCT04629833: Treatment of Steroid-Refractory Acute Graft-versus-host Disease with Mesenchymal Stromal Cells Versus Best Available Therapy
Official title: A Randomised, Open-label, Multicentre, Phase 3 Trial of First-line Treatment with Mesenchymal Stromal Cells MC0518 Versus Best Available Therapy in Adult and Adolescent Subjects with Steroid-refractory Acute Graft-versus-host Disease After Allogeneic Haematopoietic Stem Cell Transplantation (IDUNN Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Steroid-refractory Acute Graft-versus-host Disease
Lead sponsor: medac GmbH
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 210
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Overall Response (OR)
timeFrame: Day 28
measure: Overall Survival
timeFrame: Up to Month 24
Secondary outcomes:
measure: Freedom from Treatment Failure (FFTF)
timeFrame: Up to 6 months
measure: Acute Graft-versus-host Disease (aGvHD) Response
timeFrame: Days 28, 60, 100 and 180
measure: Change from Baseline in aGvHD Grades
timeFrame: Baseline and Days 8, 15, 22, 28, 60, 100 and 180
measure: Time to Response
timeFrame: Up to Month 24
measure: Duration of Response
timeFrame: Up to Month 24
measure: Best Overall Response (OR)
timeFrame: Up to Day 28
measure: Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight
timeFrame: Up to Day 60 and Month 24
measure: Number of Participants with Chronic Graft-versus-host Disease (cGvHD)
timeFrame: Day 60 to Month 24
measure: Time to Chronic Graft-versus-host Disease (cGvHD)
timeFrame: Day 60 to Month 24
measure: Number of Participants with Graft Failure (GF)
timeFrame: Up to Month 24
measure: Number of Participants with Relapse or Progression in Participants with Underlying Malignant Disease
timeFrame: Up to Month 24
measure: Time to Relapse or Progression in Participants with Underlying Malignant Disease
timeFrame: Up to Month 24
measure: Event-free survival (EFS)
timeFrame: Up to Month 24
measure: Non-relapse Mortality (NRM)
timeFrame: Up to Month 24
measure: Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs)
timeFrame: Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24)
measure: Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) by Severity
timeFrame: Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24)
measure: Change from Baseline in Performance score based on Karnofsky scale (recipient age >= 16 years)
timeFrame: Baseline, Days 8, 15, 22, 28, 60 and 100
measure: Change from Baseline in Performance score based on Lansky Scale
timeFrame: Baseline, Days 8, 15, 22, 28, 60 and 100
measure: Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Health Status Index (HSI)
timeFrame: Baseline, Days 28, 60, 100 and 180
measure: Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Visual Analogue Scale (VAS)
timeFrame: Baseline, Days 28, 60, 100 and 180
measure: Change from Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Score
timeFrame: Baseline, Days 28, 60, 100 and 180
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud
city: Besancon
country: France
facility: CHU Jean Minjoz
city: Grenoble
country: France
facility: Hopital Michallon
city: Lille
country: France
facility: CHRU Lille- Hopital Claude Huriez
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Nice
country: France
facility: CHU de Nice Hopital Archet 1
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud Pavillon Marcel Berard 1G
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire CHU de Toulouse
city: Vandoeuvre les Nancy
country: France
facility: Hopitaux De Brabois
city: Munich
country: Germany
facility: Klinikum rechts der Isar
state: Bavaria
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II - Zentrum fuer Allogene Blutstammzelltransplantation
state: Bavaria
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet - Frankfurt am Main
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen - Klinik fuer Knochenmarktransplantation (KMT)
state: North Rhine-Westphalia
city: Koeln
country: Germany
facility: Uniklinik Koeln
state: North Rhine-Westphalia
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig, Selbststaendige Abteilung fur Haematologie und Internistische Onkologie
state: Saxony
city: Jena
country: Germany
facility: Universitaetsklinikum Jena Klinik fuer Innere Medizin II, Haematologie und Onkologie
state: Thueringen
city: Jena
country: Germany
facility: Universitaetsklinikum Jena - Klinik fuer Paediatrische Haematologie und Onkologie
state: Thueringen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Bonn
country: Germany
facility: University Hospital Bonn, Medizinische Klinik III
city: Essen
country: Germany
facility: Universitaetsklinikum Essen - Klinik fuer Paediatrische Haematologie und Onkologie
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe University - University - Klinik fuer Paediatrische Haematologie und Onkologie
city: Freiburg im Breisgau
country: Germany
facility: Universitaetsklinikum Freiburg - Zentrum fuer Kinder- und Jugendmedizin (ZKJ) - Klinik fuer Paediatrische Haematologie und Onkologie
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Kiel
country: Germany
facility: Universitatsklinikum
city: Mainz
country: Germany
facility: University Medical Center Mainz
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen Medical Center
city: Wrocław
country: Poland
facility: Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University
state: Dolnoslaskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie, Paastwowy Instytut Badawczy
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Universitario Vall dHebron
city: Barcelona
country: Spain
facility: Institut Catal dOncologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Puerta De Hierro
city: Málaga
country: Spain
facility: Hospital Universitario Carlos Haya
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i politecnic La Fe
city: Huddinge
country: Sweden
facility: Center for Allogeneic Stem Cell Transplantation and Cell Therapy (CAST), Karolinska Universitetssjukhuset Huddinge
Study officials:
affiliation: Syneos Health
name: Dmitrii Tkachenko
role: STUDY_DIRECTOR
References: