Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age12+
Sponsormedac GmbH
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
MC0518
Biological/VaccineMC0518 will be intravenously infused immediately after thawing.
BAT
Biological/VaccineBAT including MMF, ECP, ATG, everolimus, and RUX will be administered based on Investigator's decision.
Treatment groups
210 Participants
are divided into 2 treatment groupsGroup A: MC0518Experimental treatment 1 intervention
Group B: Best Available Therapy (BAT)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Day 282
Overall Survival
Overall survival is defined as the time from randomization to the date of death due to any cause.
Time frame
Up to Month 24Secondary outcomes
1
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.
Time frame
Up to 6 months2
Acute Graft-versus-host Disease (aGvHD) Response
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.
Time frame
Days 28, 60, 100 and 1803
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.
Time frame
Baseline and Days 8, 15, 22, 28, 60, 100 and 1804
Time to Response
Time to response is defined as the time from the date of the first treatment administration to the date of response.
Time frame
Up to Month 24 Source ClinicalTrials.gov