Clinical trial NCT06075706: Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants with Steroid-Refractory Acute Graft Versus Host Disease
Official title: A Randomised, Open-label, Controlled, Multicentre, Phase 2 Trial of First-line Treatment with Mesenchymal Stromal Cells MC0518 Versus Best Available Therapy in Paediatric Participants with Steroid-refractory Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation (BALDER Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Steroid-refractory Acute Graft-versus-host Disease
Lead sponsor: medac GmbH
Sponsor class: INDUSTRY
First posted: 2023-10-10
Enrollment: 48
Sex: ALL
Minimum age (years): 28
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is the comparative evaluation of overall response rate (ORR) in paediatric participants with steroid-refractory acute graft-versus-host disease (SR-aGvHD) at Visit Day 28 after treatment with MC0518 or first used best available therapy (BAT).


Eligibility criteria: Inclusion Criteria:

1. 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 hematological malignant disease or neuroblastoma.
2. Participant has been clinically diagnosed with Grade II to IV aGvHD according to Harris et al. A biopsy of the involved organs with aGvHD is encouraged but not required.
3. Participant has experienced failure of previous first-line aGvHD treatment (that is, SR-aGvHD), defined as:

   * aGvHD progression within 3 to 5 days of therapy onset with \>=2 milligram per kilogram per day (mg/kg/day) of prednisone equivalent or
   * failure to improve within 5 to 7 days of treatment initiation with \>=2 mg/kg/day of prednisone equivalent or
   * incomplete response after greater than (\>) 28 days of immunosuppressive treatment including at least 5 days with \>=2 mg/kg/day of prednisone equivalent.
4. Male or female participant who is \>=28 days and \<18 years of age and has a minimum body weight of 3.2 kilograms (kg) at the Screening Visit.
5. Participant has an estimated life expectancy of \>28 days.
6. Participant, if female and of childbearing potential, agrees to use a highly effective contraceptive measure starting at the Screening Visit and continuing throughout the entire trial period.
7. Participant, if a fertile male, agrees to sexual abstinence or to use a condom during sexual activity with their female partner of childbearing potential or pregnant partner. Additionally, if their partner is a woman of childbearing potential (WOCBP), then their partner must use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period.
8. A written informed consent of the participant's parent(s) / legal guardian(s) (and participant's assent, when applicable) has been obtained according to national regulations.

Exclusion Criteria:

1. Participant has overt relapse or progression or persistence of the underlying disease.
2. Participant has received the last HSCT for a solid tumor disease other than neuroblastoma.
3. Participant has graft-versus-host disease overlap syndrome.
4. 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, mycophenolate mofetil, methotrexate, abatacept, or cyclophosphamide. Note: In vitro or in vivo graft manipulation to prevent graft-versus-host disease (example, T-cell depletion) during HSCT is permitted. Restart of initial prophylaxis with calcineurin inhibitors, mammalian target of rapamycin inhibitors, or mycophenolate mofetil after aGvHD onset is permitted.
5. Participant has received prior mesenchymal stromal cell (MSC) treatment, including MC0518/Obnitix®.
6. Participant has a known pregnancy (as confirmed by a positive pregnancy test result at the Screening Visit) and / or is breastfeeding.
7. Participant has a known hypersensitivity to MC0518 and / or its excipients (dimethyl sulfoxide, human serum albumin, isotonic sodium chloride solution).
8. Participant has a known hypersensitivity or any contraindication to the Investigator's choice BAT (extracorporeal photopheresis, anti thymocyte globulin, etanercept, infliximab, or ruxolitinib) and / or its excipients. For a list of excipients please refer to the respective Summary of Product Characteristics.
9. Participant has an underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant.
10. Participant has an uncontrolled infection (examples, sepsis or multi-organ failure) including significant bacterial, fungal, viral, or parasitic infection requiring treatment.
11. Participant has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit.

Primary outcomes:
measure: Number of Participants With Overall Response (OR)
timeFrame: At Day 28
Secondary outcomes:
measure: Number of Participants With Freedom From Treatment Failure (FFTF) Until 6 Months (Day 180)
timeFrame: Up to 6 months (Day 180)
measure: Overall Survival (OS)
timeFrame: Up to Month 24
measure: Number of Participants With aGvHD Response
timeFrame: At Days 28, 60, 100 and 180
measure: Change From Baseline in aGvHD Grades
timeFrame: Baseline, Days 8, 15, 22, 28, 60, 100 and 180
measure: Time to Response
timeFrame: From the date of the first treatment administration to the date of the first response (CR or PR) (up to 5 years)
measure: Duration of Response
timeFrame: Up to Month 24
measure: Number of Participants With Best Overall Response (OR)
timeFrame: Up to Day 28
measure: Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight
timeFrame: From the date of the first treatment administration up to Day 28, Day 60, and Month 24
measure: Number of Participants With Chronic Graft-versus-host Disease (cGvHD)
timeFrame: From Day 60 up to Month 24
measure: Time to Chronic Graft-versus-host Disease (cGvHD)
timeFrame: From Day 60 up to Month 24
measure: Number of Participants With Graft Failure (GF)
timeFrame: Baseline up to Month 24
measure: Number of Participants With Relapse or Progression in Participants With Underlying Malignant Disease
timeFrame: From randomization up to Month 24
measure: Time to Relapse or Progression in Participants With Underlying Malignant Disease
timeFrame: From randomization up to Month 24
measure: Event-free Survival (EFS)
timeFrame: From the date of randomization to date of GF, relapse or progression of the underlying disease, or death due to any cause, whichever occurs first (up to Month 24)
measure: Non-relapse Mortality (NRM)
timeFrame: From the date of randomization to the date of death without previous relapse or progression of the underlying disease (up to Month 24)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to Month 24
measure: Number of Participants With Adverse Reactions (ARs) by Severity
timeFrame: Up to Month 24
measure: Change From Baseline in Performance Score Based on Karnofsky Scale
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: Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scale Score
timeFrame: Baseline, Days 28, 60, 100 and 180
measure: Change From Baseline in PedsQL™ Stem Cell Transplant Module Scale Score
timeFrame: Baseline, Days 28, 60, 100 and 180
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hopital des Enfants
city: La Tronche
country: France
facility: CHU Grenoble Alpes - Hopital Couple Enfant (HCE)
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille CHU Lille - Hopital Jeanne de Flandre HJF
city: Lyon
country: France
facility: Institut d'Hematologie et d'Oncologie Pediatrique (IHOPe)
city: Marseille
country: France
facility: CHU de Marseille-Hopital de la Timone
city: Montpellier
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) Montpellier - hopital Arnaud de Villeneuve
city: Nantes Cedex 01
country: France
facility: CHU de Nantes - Hopital Mere Enfant
city: Paris
country: France
facility: Hopital Robert Debre
city: Rennes
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Rouen
country: France
facility: CHU de Rouen - Hopital Charles Nicolle
city: Strasbourg
country: France
facility: CHRU de Strasbourg - Hopital de Hautepierre
city: Vandoeuvre-les-Nancy
country: France
facility: CHRU Nancy, Hopitaux de Brabois
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen, Klinik fur Kinder- und Jugendmedizin
city: Dusseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg - Zentrum fuer Kinder- und Jugendmedizin (ZKJ)
city: Giessen
country: Germany
facility: Justus-Liebig-Universitaet Giessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover MHH
city: Jena
country: Germany
facility: Department of Pediatrics, Jena University Hospital
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig - Abteilung fuer Paediatrische Onkologie, Haematologie und Haemostaseologie
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster (UKM) - Klinik fuer Kinder- und Jugendmedizin - Paediatrische Haematologie und Onkologie
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi
city: Monza
country: Italy
facility: Pediatric Clinic Onco Hematology San Gerardo Hospital
city: Pavia
country: Italy
facility: U.O.C. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo
city: Rome
country: Italy
facility: Hematology and Cellular Therapy Ospedale Bambino Gesu
city: Turin
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino Ospedale Infantile Regina Margherita
city: Wroclaw
country: Poland
facility: Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University
state: Dolnoslaskie
city: Lublin
country: Poland
facility: Dzieciecy Szpital Kliniczny im. A.Gebali w Lublinie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Karola Jonschera UM
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall dHebron
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu Barcelona (HSJDB)
city: Madrid
country: Spain
facility: Hospital NiÃ±o Jesus
city: Madrid
country: Spain
facility: Hospital Infantil Universitario La Paz
city: Malaga
country: Spain
facility: Instituto de Investigacion Biomedica de Malaga IBIMA - sede Hospital Regional Universitario de Malaga HRUM Hospital Carlos Haya
city: Murcia
country: Spain
facility: Instituto Murciano de Investigacion Biosanitaria (IMIB) Virgen de la Arrixaca
city: Valencia
country: Spain
facility: Hospital Universitari I politecnic La Fe Jose
Study officials:
References: