Trial of efficacy and safety of MC0518 versus best available therapy in patients with steroid-refractory acute graft versus host disease
- Conditions
- Steroid refractory Acute Graft versus host Disease
- Registration Number
- 2023-503952-28-00
- Lead Sponsor
- Medac Gesellschaft fuer klinische Spezialprapaerate mbH
- Brief Summary
Comparative evaluation of the overall response rate in paediatric participants with steroid-refractory acute graft-versus-host disease (SR aGvHD) at Visit Day 28 after treatment with MC0518 or first used best available therapy (BAT)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 54
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 or neuroblastoma.
Participant has been clinically diagnosed with Grade II to IV aGvHD according to Harris et al. A biopsy of the involved organs with aGvHD is encouraged but not required.
Participant has experienced failure of previous first line aGvHD treatment (ie, SR aGvHD), defined as: - aGvHD progression within 3 to 5 days of therapy onset with ≥ 2 mg/kg/day of prednisone equivalent or - failure to improve within 5 to 7 days of treatment initiation with ≥ 2 mg/kg/day of prednisone equivalent or - incomplete response after > 28 days of immunosuppressive treatment including at least 5 days with ≥ 2 mg/kg/day of prednisone equivalent.
Male or female participant who is ≥ 28 days and < 18 years of age and has a minimum BW of 3.2 kg at the Screening Visit.
Participant has an estimated life expectancy of > 28 days.
Participant, if female and of childbearing potential, agrees to use a highly effective contraceptive measure starting at the Screening Visit and continuing throughout the entire trial period. The definition of women of childbearing potential and a complete list of highly effective contraceptive measures are included in an appendix to the protocol.
Participant, if a fertile male, agrees to sexual abstinence or to use a condom during sexual activity with their female partner of childbearing potential or pregnant partner. Additionally, if their partner is a woman of childbearing potential, then their partner must use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period. The definition of fertile men and a complete list of highly effective contraceptive measures are included in an appendix to the protocol.
A written informed consent of the participant’s parent(s) / legal guardian(s) (and participant’s assent, when applicable) has been obtained according to national regulations.
Participant has overt relapse or progression or persistence of the underlying disease.
Participant has an uncontrolled infection (eg, sepsis or multi-organ failure) including significant bacterial, fungal, viral, or parasitic infection requiring treatment.
Participant has received treatment with any other investigational agent within 30 days or 5 half lives (whichever is longer) before the Screening Visit
Participant has received the last HSCT for a solid tumour disease other than neuroblastoma.
Participant has graft-versus-host disease overlap syndrome as defined by Jagasia et al.
Participant has received systemic first line treatment for aGvHD other than steroids and a prophylaxis with other than calcineurin inhibitors, mammalian target of rapamycin inhibitors, anti thymocyte globulin, mycophenolate mofetil, methotrexate, abatacept, or cyclophosphamide. Please Note: In vitro or in vivo graft manipulation to prevent graft-versus-host disease (eg, T cell depletion) during HSCT is permitted. Restart of initial prophylaxis with calcineurin inhibitors, mammalian target of rapamycin inhibitors, or mycophenolate mofetil after aGvHD onset is permitted.
Participant has received prior mesenchymal stromal cell (MSC) treatment, including MC0518/Obnitix®.
Participant has a known pregnancy (as confirmed by a positive pregnancy test result at the Screening Visit) and / or is breastfeeding.
Participant has a known hypersensitivity to MC0518 and / or its excipients (dimethyl sulfoxide, human serum albumin, isotonic sodium chloride solution).
Participant has a known hypersensitivity or any contraindication to the Investigator’s choice BAT (extracorporeal photopheresis, anti thymocyte globulin, etanercept, infliximab, or ruxolitinib) and / or its excipients. For a list of excipients please refer to the respective Summary of Product Characteristics.
Participant has an underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant.
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall response (OR), defined as complete response (CR) or partial response (PR) at Visit Day 28 relative to the aGvHD status at baseline (Visit Day 1 prior to the first treatment). Overall response (OR), defined as complete response (CR) or partial response (PR) at Visit Day 28 relative to the aGvHD status at baseline (Visit Day 1 prior to the first treatment).
- Secondary Outcome Measures
Name Time Method Freedom from treatment failure until 6 months (Visit Day 180), defined as the time from the date of randomisation to the date of the event. An event is defined as death, relapse or progression of the underlying disease, or addition of or change to any further systemic aGvHD therapy (except changes in steroid treatment). The diagnosis of cGvHD is a competing event Freedom from treatment failure until 6 months (Visit Day 180), defined as the time from the date of randomisation to the date of the event. An event is defined as death, relapse or progression of the underlying disease, or addition of or change to any further systemic aGvHD therapy (except changes in steroid treatment). The diagnosis of cGvHD is a competing event
OS until Visit Month 24, defined as the time from the date of randomisation to the date of death due to any cause OS until Visit Month 24, defined as the time from the date of randomisation to the date of death due to any cause
aGvHD response at Visit Day 28 assessed by CR, PR, and NR and at Visit Day 60, Visit Day 100, and Visit Day 180 assessed by OR, CR, PR, and NR relative to baseline aGvHD response at Visit Day 28 assessed by CR, PR, and NR and at Visit Day 60, Visit Day 100, and Visit Day 180 assessed by OR, CR, PR, and NR relative to baseline
Change of aGvHD grade at Visit Day 8, Visit Day 15, Visit Day 22, Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 relative to baseline Change of aGvHD grade at Visit Day 8, Visit Day 15, Visit Day 22, Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 relative to baseline
Time to response, defined as the time from the date of the first treatment administration to the date of the first response (CR or PR) Time to response, defined as the time from the date of the first treatment administration to the date of the first response (CR or PR)
Duration of response until Visit Month 24, defined as the time from the date of the first OR (CR or PR) to the date of aGvHD assessed as NR compared to the baseline assessment, or the date of addition of or change to any further systemic aGvHD therapy (except changes in steroid treatment), in responders Duration of response until Visit Month 24, defined as the time from the date of the first OR (CR or PR) to the date of aGvHD assessed as NR compared to the baseline assessment, or the date of addition of or change to any further systemic aGvHD therapy (except changes in steroid treatment), in responders
Best OR until Visit Day 28, defined as the achievement of an OR at any time point up to and including Visit Day 28 Best OR until Visit Day 28, defined as the achievement of an OR at any time point up to and including Visit Day 28
Cumulative dose of steroids given for SR-aGvHD per kg body weight (BW) from the date of the first treatment administration until Visit Day 28, Visit Day 60, and until Visit Month 24 Cumulative dose of steroids given for SR-aGvHD per kg body weight (BW) from the date of the first treatment administration until Visit Day 28, Visit Day 60, and until Visit Month 24
Incidence of and time to cGvHD from Visit Day 60 until Visit Month 24 Incidence of and time to cGvHD from Visit Day 60 until Visit Month 24
Incidence of graft failure (GF) from baseline until Visit Month 24 Incidence of graft failure (GF) from baseline until Visit Month 24
Incidence of and time to relapse or progression of the underlying disease in participants with underlying malignant disease from randomisation until Visit Month 24 Incidence of and time to relapse or progression of the underlying disease in participants with underlying malignant disease from randomisation until Visit Month 24
Event free survival until Visit Month 24, defined as the time from the date of randomisation 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 Event free survival until Visit Month 24, defined as the time from the date of randomisation 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
Non-relapse mortality until Visit Month 24, 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. Relapse or progression are competing events Non-relapse mortality until Visit Month 24, 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. Relapse or progression are competing events
The incidence and severity of all adverse events (AEs), including viral, bacterial, and fungal infections until Visit Day 60, and of adverse reactions (ARs) until Visit Month 24 The incidence and severity of all adverse events (AEs), including viral, bacterial, and fungal infections until Visit Day 60, and of adverse reactions (ARs) until Visit Month 24
Performance score (Karnofsky / Lansky scale) at Visit Day 8, Visit Day 15, Visit Day 22, Visit Day 28, Visit Day 60, and Visit Day 100 compared to baseline Performance score (Karnofsky / Lansky scale) at Visit Day 8, Visit Day 15, Visit Day 22, Visit Day 28, Visit Day 60, and Visit Day 100 compared to baseline
HRQoL measures: Paediatric Quality of Life InventoryTM (PedsQL™) 4.0 Generic Core Scales with the PedsQL™ Stem Cell Transplant Module at Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 compared to baseline HRQoL measures: Paediatric Quality of Life InventoryTM (PedsQL™) 4.0 Generic Core Scales with the PedsQL™ Stem Cell Transplant Module at Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 compared to baseline
Trial Locations
- Locations (38)
Robert Debre University Hospital
🇫🇷Paris, France
Hospices Civils De Lyon
🇫🇷Lyon, France
Centre Hospitalier Universitaire De Nantes
🇫🇷Nantes, France
Centre Hospitalier Universitaire De Bordeaux
🇫🇷Bordeaux, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille Cedex, France
Assistance Publique Hopitaux De Marseille
🇫🇷Marseille, France
CHRU De Nancy
🇫🇷Vandoeuvre Les Nancy, France
Centre Hospitalier Universitaire Grenoble Alpes
🇫🇷Grenoble Cedex 9, France
CHU De Rouen
🇫🇷Rouen Cedex, France
Les Hopitaux Universitaires De Strasbourg
🇫🇷Strasbourg Cedex 2, France
Scroll for more (28 remaining)Robert Debre University Hospital🇫🇷Paris, FranceJean-Hugues DALLESite contact+33140033692jean-hugues.dalle@aphp.fr