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

Medac

Status and phase: Enrolling; Phase 3

Conditions: Steroid-refractory Acute Graft-versus-host Disease

Treatments: Biological: BAT; Biological: MC0518

Study type: Interventional

Funder types: Industry

Identifiers

NCT04629833

MC-MSC.1/aGvHD

Details and patient eligibility

About

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).

Enrollment: 210 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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210 participants in 2 patient groups

MC0518

Experimental group

Description:

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.

Treatment:

Biological: MC0518

Best Available Therapy (BAT)

Active Comparator group

Description:

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).

Treatment:

Biological: BAT