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

Официальное название

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)

Обзор

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).

Вмешательства

• Биопрепарат MC0518
  MC0518 will be intravenously infused immediately after thawing.
• Биопрепарат BAT
  BAT including MMF, ECP, ATG, everolimus, and RUX will be administered based on Investigator's decision.

Первичные конечные точки

• Overall Response (OR) [Срок оценки: Day 28]
• Overall Survival [Срок оценки: Up to Month 24]

Вторичные конечные точки (12)

• Freedom from Treatment Failure (FFTF) [Срок оценки: Up to 6 months]
• Acute Graft-versus-host Disease (aGvHD) Response [Срок оценки: Days 28, 60, 100 and 180]
• Change from Baseline in aGvHD Grades [Срок оценки: Baseline and Days 8, 15, 22, 28, 60, 100 and 180]
• Time to Response [Срок оценки: Up to Month 24]
• Duration of Response [Срок оценки: Up to Month 24]
• Best Overall Response (OR) [Срок оценки: Up to Day 28]
• Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight [Срок оценки: Up to Day 60 and Month 24]
• Number of Participants with Chronic Graft-versus-host Disease (cGvHD) [Срок оценки: Day 60 to Month 24]
• Time to Chronic Graft-versus-host Disease (cGvHD) [Срок оценки: Day 60 to Month 24]
• Number of Participants with Graft Failure (GF) [Срок оценки: Up to Month 24]
• Number of Participants with Relapse or Progression in Participants with Underlying Malignant Disease [Срок оценки: Up to Month 24]
• Time to Relapse or Progression in Participants with Underlying Malignant Disease [Срок оценки: Up to Month 24]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 22 центра

• Klinikum rechts der Isar — Munich
• Universitaetsklinikum Wuerzburg - Medizinische Klinik und Poliklinik II - Zentrum fuer All — Würzburg
• Klinikum der Johann Wolfgang Goethe-Universitaet - Frankfurt am Main — Frankfurt am Main
• Medizinische Hochschule Hannover — Hanover
• Uniklinik Koeln — Cologne
• Universitaetsklinikum Essen - Klinik fuer Knochenmarktransplantation (KMT) — Essen
• Universitaetsklinikum Muenster — Münster
• Universitaetsklinikum Carl Gustav Carus Dresden — Dresden
• … и ещё 14 центров

Франция · 9 центров

• Centre Hospitalier Universitaire (CHU) Amiens-Picardie - Hopital Sud — Amiens
• CHU Jean Minjoz — Besançon
• Hopital Michallon — Grenoble
• CHRU Lille- Hopital Claude Huriez — Lille
• CHU de Nantes - Hotel Dieu — Nantes
• CHU de Nice Hopital Archet 1 — Nice
• Centre Hospitalier Lyon Sud Pavillon Marcel Berard 1G — Pierre-Bénite
• Centre Hospitalier Universitaire CHU de Toulouse — Toulouse
• … и ещё 1 центр

Испания · 8 центров

• Hospital Germans Trias i Pujol — Badalona
• Hospital Universitario Vall dHebron — Barcelona
• Institut Catal dOncologia — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Puerta De Hierro — Madrid
• Hospital Universitario Carlos Haya — Málaga
• Hospital Clinico Universitario de Valencia — Valencia
• Hospital Universitari i politecnic La Fe — Valencia

Польша · 2 центра

• Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University — Wroclaw
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie, Paastwowy Instytut Badawczy — Gliwice

Швеция · 1 центр

• Center for Allogeneic Stem Cell Transplantation and Cell Therapy (CAST), Karolinska Univer — Huddinge

Идентификаторы

NCT: NCT04629833 · MC-MSC.1/aGvHD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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