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)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- medac GmbH
- 入组人数
- 210
- 试验地点
- 42
- 主要终点
- Overall Survival
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
MC0518
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.
干预措施: MC0518 (Biological)
Best Available Therapy (BAT)
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).
干预措施: BAT (Biological)
结局指标
主要结局
Overall Survival
时间窗: Up to Month 24
Overall survival is defined as the time from randomization to the date of death due to any cause.
Overall Response (OR)
时间窗: Day 28
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.
次要结局
- Time to Response(Up to Month 24)
- Duration of Response(Up to Month 24)
- Best Overall Response (OR)(Up to Day 28)
- Time to Chronic Graft-versus-host Disease (cGvHD)(Day 60 to Month 24)
- Number of Participants with Graft Failure (GF)(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))
- Freedom from Treatment Failure (FFTF)(Up to 6 months)
- Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight(Up to Day 60 and Month 24)
- Event-free survival (EFS)(Up to Month 24)
- Non-relapse Mortality (NRM)(Up to Month 24)
- Number of Participants with Adverse Events (AEs) and Adverse Reactions (ARs) by Severity(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 Lansky Scale(Baseline, Days 8, 15, 22, 28, 60 and 100)
- Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Visual Analogue Scale (VAS)(Baseline, Days 28, 60, 100 and 180)
- Number of Participants with Chronic Graft-versus-host Disease (cGvHD)(Day 60 to Month 24)
- 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)
- Number of Participants with Relapse or Progression in Participants with Underlying Malignant Disease(Up to Month 24)
- Time to Relapse or Progression in Participants with Underlying Malignant Disease(Up to Month 24)
- Change from Baseline in Performance score based on Karnofsky scale (recipient age >= 16 years)(Baseline, Days 8, 15, 22, 28, 60 and 100)
- Change from Baseline in EuroQol-5D-5L (EQ-5D-5L): Health Status Index (HSI)(Baseline, Days 28, 60, 100 and 180)
- Change from Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) Score(Baseline, Days 28, 60, 100 and 180)