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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MC0518 | Biological | MC0518 will be intravenously infused immediately after thawing. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Freedom from Treatment Failure (FFTF) | FFTF is defined as death, relapse or progression of the underlying disease, or addition or change to any further systemic immunosuppressive aGvHD therapy. Number of participants with FFTF will be reported. | Up to 6 months |
| Acute Graft-versus-host Disease (aGvHD) Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Information | Contact | +49 40103 8006-0 | ClinicalTrialInformation@medac.de |
| Name | Affiliation | Role |
|---|---|---|
| Ann-Kristin Möller | medac GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud | Recruiting | Amiens | 80054 | France |
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| BAT |
| Biological |
BAT including MMF, ECP, ATG, everolimus, and RUX will be administered based on Investigator's decision. |
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Number of participants with aGvHD response will be reported. aGvHD response will be categorized as OR (CR + PR), CR, PR, and NR. NR is defined as the absence of CR or PR. |
| Days 28, 60, 100 and 180 |
| Change from Baseline in aGvHD Grades | aGvHD grades: Grade 0- no organ involvement (ie, Stage 0 skin, Stage 0 liver, and Stage 0 GI); Grade I-Stage 1 - 2 skin without liver/GI involvement; Grade II- Stage 3 skin and / or Stage 1 liver and / or Stage 1 GI; Grade III- Stage 2 - 3 liver and / or Stage 2 - 3 GI; Grade IV- Stage 4 skin and / or Stage 4 liver and/or Stage 4 GI. | Baseline and Days 8, 15, 22, 28, 60, 100 and 180 |
| Time to Response | Time to response is defined as the time from the date of the first treatment administration to the date of response. | Up to Month 24 |
| Duration of Response | Duration is calculated from time from the first OR (CR or PR) until the time point of no aGvHD response in comparison to baseline. | Up to Month 24 |
| Best Overall Response (OR) | Best OR is defined as the achievement of an OR at any time point up to and including Day 28. Number of participants with best OR will be reported. | Up to Day 28 |
| Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight | The cumulative dose of steroids given for SR-aGvHD per kg of body weight from baseline until Day 60 and until Visit Month 24 will be analyzed. | Up to Day 60 and Month 24 |
| Number of Participants with Chronic Graft-versus-host Disease (cGvHD) | Number of participants with cGvHD will be reported. | Day 60 to Month 24 |
| Time to Chronic Graft-versus-host Disease (cGvHD) | Time to cGvHD is defined as the time between the last day of haematopoietic stem cell transplantation (HSCT) to the first episode of cGvHD. | Day 60 to Month 24 |
| Number of Participants with Graft Failure (GF) | Number of participants with GF will be reported. | Up to Month 24 |
| Number of Participants with Relapse or Progression in Participants with Underlying Malignant Disease | Number of participants with relapse or progression in participants with underlying malignant disease will be reported. | Up to Month 24 |
| Time to Relapse or Progression in Participants with Underlying Malignant Disease | Time to relapse or progression in participants with underlying malignant disease will be reported. | Up to Month 24 |
| Event-free survival (EFS) | EFS is defined as the time from the date of randomization to the date of the event. An event is defined as GF, relapse or progression of the underlying disease, or death due to any cause. | Up to Month 24 |
| Non-relapse Mortality (NRM) | NRM is defined as the time from the date of randomisation to the date of the event. An event is defined as death without previous relapse or progression of the underlying disease. | Up to Month 24 |
| Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) | Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24) |
| Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) by Severity | Severity will be graded based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening consequences; urgent intervention indicated; Grade 4- Death related to the AE. | Until Day 60 or until 30 days after last administration of trial treatment, whichever is later (Up to Month 24) |
| Change from Baseline in Performance score based on Karnofsky scale (recipient age >= 16 years) | The Karnofsky performance score (KPS), which is reported on an ordinal scale from 0 to 100, provides a rough measure of the participant's well-being, including their ability to conduct activities of daily living and functional capacity. Higher score indicates normal, no complaints and no evidence of disease. | Baseline, Days 8, 15, 22, 28, 60 and 100 |
| Change from Baseline in Performance score based on Lansky Scale | A Lansky score (recipient age greater than or equal to [>=] 1 years and less than [<] 16 years) will be recorded pre-treatment and measured serially at regular intervals after treatment. The score is a standard performance score that measures overall function of the child with a scale range from 0 to 100. Higher score indicates full activeness. | Baseline, Days 8, 15, 22, 28, 60 and 100 |
| Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Health Status Index (HSI) | EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "TODAY". Responses were used to generate a HSI. HSI ranges from 0 (dead) to 1.00 (full health). | Baseline, Days 28, 60, 100 and 180 |
| Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Visual Analogue Scale (VAS) | EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). | Baseline, Days 28, 60, 100 and 180 |
| Change from Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Score | The FACT-BMT questionnaire was designed to measure the quality of life in subjects undergoing bone marrow (BM) transplantation. It consists of the following categories of assessment: physical well-being, social / family well-being, emotional well-being, functional well-being, and additional miscellaneous concerns that the subject may have concerning their healthcare, persons involved in their life, and other emotions and incapabilities. Score ranges from 0-164, with higher score indicating better quality of life. | Baseline, Days 28, 60, 100 and 180 |
| CHU Jean Minjoz | Recruiting | Besançon | 25030 | France |
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| Hopital Michallon | Recruiting | Grenoble | 38700 | France |
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| CHRU Lille- Hopital Claude Huriez | Recruiting | Lille | 59000 | France |
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| CHU de Nantes - Hotel Dieu | Recruiting | Nantes | 44093 | France |
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| CHU de Nice Hopital Archet 1 | Recruiting | Nice | 06200 | France |
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| Centre Hospitalier Lyon Sud Pavillon Marcel Berard 1G | Recruiting | Pierre-Bénite | 69630 | France |
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| Centre Hospitalier Universitaire CHU de Toulouse | Recruiting | Toulouse | 31059 | France |
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| Hopitaux De Brabois | Recruiting | Vandœuvre-lès-Nancy | 54511 | France |
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| Klinikum rechts der Isar | Recruiting | Munich | Bavaria | 81675 | Germany |
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| Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II - Zentrum fuer Allogene Blutstammzelltransplantation | Recruiting | Würzburg | Bavaria | 97080 | Germany |
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| Klinikum der Johann Wolfgang Goethe-Universitaet - Frankfurt am Main | Recruiting | Frankfurt am Main | Hesse | 60590 | Germany |
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| Medizinische Hochschule Hannover | Recruiting | Hanover | Lower Saxony | 30625 | Germany |
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| Uniklinik Koeln | Active, not recruiting | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Universitaetsklinikum Essen - Klinik fuer Knochenmarktransplantation (KMT) | Recruiting | Essen | North Rhine-Westphalia | 45147 | Germany |
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| Universitaetsklinikum Muenster | Recruiting | Münster | North Rhine-Westphalia | 48149 | Germany |
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| Universitaetsklinikum Carl Gustav Carus Dresden | Recruiting | Dresden | Saxony | 01307 | Germany |
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| Universitaetsklinikum Leipzig, Selbststaendige Abteilung fur Haematologie und Internistische Onkologie | Recruiting | Leipzig | Saxony | 04103 | Germany |
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| Universitaetsklinikum Jena Klinik fuer Innere Medizin II, Haematologie und Onkologie | Recruiting | Jena | Thuringia | 07740 | Germany |
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| Universitaetsklinikum Jena - Klinik fuer Paediatrische Haematologie und Onkologie | Terminated | Jena | Thuringia | 07747 | Germany |
| Charite Universitaetsmedizin | Withdrawn | Berlin | 13353 | Germany |
| Helios Klinikum Berlin-Buch | Recruiting | Berlin | 287706 | Germany |
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| University Hospital Bonn, Medizinische Klinik III | Recruiting | Bonn | 53127 | Germany |
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| Universitaetsklinikum Essen - Klinik fuer Paediatrische Haematologie und Onkologie | Terminated | Essen | 45147 | Germany |
| Klinikum der Johann Wolfgang Goethe University - University - Klinik fuer Paediatrische Haematologie und Onkologie | Recruiting | Frankfurt | 60590 | Germany |
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| Universitaetsklinikum Freiburg - Zentrum fuer Kinder- und Jugendmedizin (ZKJ) - Klinik fuer Paediatrische Haematologie und Onkologie | Terminated | Freiburg im Breisgau | 151595 | Germany |
| Universitaetsklinikum Freiburg | Recruiting | Freiburg im Breisgau | 79106 | Germany |
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| Universitatsklinikum | Recruiting | Kiel | 24105 | Germany |
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| University Medical Center Mainz | Recruiting | Mainz | 55131 | Germany |
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| Universitaetsklinikum Mannheim | Recruiting | Mannheim | 68167 | Germany |
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| University Hospital Tuebingen Medical Center | Recruiting | Tübingen | 72076 | Germany |
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| Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University | Terminated | Wroclaw | Lower Silesian Voivodeship | 50-556 | Poland |
| Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie, Paastwowy Instytut Badawczy | Recruiting | Gliwice | 44-102 | Poland |
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| Hospital Germans Trias i Pujol | Recruiting | Badalona | 08916 | Spain |
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| Hospital Universitario Vall dHebron | Recruiting | Barcelona | 08035 | Spain |
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| Institut Catal dOncologia | Recruiting | Barcelona | 08908 | Spain |
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| Hospital Universitario Ramon y Cajal | Recruiting | Madrid | 28034 | Spain |
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| Hospital Puerta De Hierro | Recruiting | Madrid | 28222 | Spain |
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| Hospital Universitario Carlos Haya | Recruiting | Málaga | 29010 | Spain |
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| Hospital Clinico Universitario de Valencia | Recruiting | Valencia | 46010 | Spain |
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| Hospital Universitari i politecnic La Fe | Recruiting | Valencia | 46026 | Spain |
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| Center for Allogeneic Stem Cell Transplantation and Cell Therapy (CAST), Karolinska Universitetssjukhuset Huddinge | Terminated | Huddinge | 126464 | Sweden |