Clinical trial • Phase III • Immunology|Rare Disease

MESENCHYMAL STROMAL CELLS, EX VIVO CULTURED for Steroid-refractory acute graft-versus-host disease|Acute graft-versus-host disease

Phase III trial of MESENCHYMAL STROMAL CELLS, EX VIVO CULTURED for Steroid-refractory acute graft-versus-host disease|Acute graft-versus-host disease.

Overview

Trial Therapeutic Area
Immunology|Rare Disease
Trial Disease
Steroid-refractory acute graft-versus-host disease|Acute graft-versus-host disease
Trial Stage
Phase III
Drug Modality
Cell therapy|Small molecule|Other antibody
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
16-02-2024
First CTIS Authorization Date
28-03-2024

Trial design

Randomised, open-label, best available therapy (bat) — investigator-selected standard of care; may include agents such as everolimus, mycophenolate mofetil, antithymocyte immunoglobulin; specific doses/schedules per investigator/bat not specified-controlled Phase III trial in Spain, Poland, France and others.

Randomised
Yes
Open Label
Yes
Comparator
Best Available Therapy (BAT) — investigator-selected standard of care; may include agents such as EVEROLIMUS, MYCOPHENOLATE MOFETIL, ANTITHYMOCYTE IMMUNOGLOBULIN; specific doses/schedules per investigator/BAT not specified
Target Sample Size
210
Trial Duration For Participant
730

Eligibility

Recruits 210 paediatric patients.

Pregnancy Exclusion
Subject has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit.
Vulnerable Population
The trial includes adolescents (subjects ≥ 12 years of age). Consent/assent handling: "Subject or parent(s) / legal guardian(s) have read, understood, and signed the informed consent form (and informed assent form, if applicable) according to national regulations." Age-specific informed consent and assent forms and parent information forms are provided (child/adolescent ICFs and parent ICFs are included in the submitted documents).

Inclusion criteria

  • {"criterion_text":"- Subject 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"}
  • {"criterion_text":"- Subject has been clinically diagnosed with Grade II to IV aGvHD at the Screening Visit."}
  • {"criterion_text":"- Subject 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."}
  • {"criterion_text":"- Male or female subject who is ≥ 12 years of age and ≥ 15 kg at the Screening Visit."}
  • {"criterion_text":"- Subject has an estimated life expectancy > 28 days at the Screening Visit."}
  • {"criterion_text":"- Subject, 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 (WOCBP) and a complete list of highly effective contraceptive measures are included in an appendix to the protocol."}
  • {"criterion_text":"- Subject, 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 WOCBP, then their partner has to use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period. For the definition of fertile men and a complete list of highly effective contraceptive measures are included in an appendix to the protocol."}
  • {"criterion_text":"- Subject or parent(s) / legal guardian(s) have read, understood, and signed the informed consent form (and informed assent form, if applicable) according to national regulations."}

Exclusion criteria

  • {"criterion_text":"- Subject has overt relapse or progression or persistence of the underlying disease at the Screening Visit."}
  • {"criterion_text":"- Subject has received the last HSCT for a solid tumour disease."}
  • {"criterion_text":"- Subject has GvHD overlap syndrome at the Screening Visit."}
  • {"criterion_text":"- Subject 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. Please Note: In vitro or in vivo graft manipulation to prevent GvHD (eg, T-cell depletion) during HSCT is permitted. Restart of initial prophylaxis with calcineurin inhibitors or mTOR inhibitors after aGvHD onset is permitted."}
  • {"criterion_text":"- Subject has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit."}
  • {"criterion_text":"- Subject has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Overall response (OR) as defined by complete response (CR) or partial response (PR) at Visit Day 28 relative to aGvHD status at baseline (Visit Day 1 before the first treatment).","definition_or_measurement_approach":"OR defined by CR or PR at Visit Day 28 compared with aGvHD status at baseline (Visit Day 1 before first treatment)."}
  • {"endpoint_text":"- OS until Visit Month 24, defined as the time from the date of randomisation to the date of death due to any cause","definition_or_measurement_approach":"Overall survival measured as time from randomisation to death from any cause, up to Visit Month 24."}

Secondary endpoints

  • {"endpoint_text":"- FFTF until 6 months, 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 or change to any further systemic immunosuppressive aGvHD therapy. The diagnosis of cGvHD is considered to be a competing event.","definition_or_measurement_approach":"Time from randomisation to event (death, relapse/progression, or addition/change of systemic aGvHD therapy) up to 6 months; cGvHD is a competing event."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessment of aGvHD response categories (CR, PR, NR, OR) at specified visits relative to baseline."}
  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Change in aGvHD grade at specified visits compared with baseline."}
  • {"endpoint_text":"- 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)","definition_or_measurement_approach":"Time from first administration to first documented CR or PR."}
  • {"endpoint_text":"- Duration of the 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 with the baseline assessment, or the date of addition or change to any further systemic aGvHD therapy, in responders.","definition_or_measurement_approach":"Time from first OR to loss of response (NR vs baseline) or addition/change of systemic aGvHD therapy, up to Month 24."}
  • {"endpoint_text":"- Best OR until Visit Day 28 defined as the achievement of an OR at any time point up to and including Visit Day 28","definition_or_measurement_approach":"Achievement of OR at any time point through Day 28."}
  • {"endpoint_text":"- Cumulative dose of steroids given for SR-aGvHD from baseline until Visit Day 60 and until Visit Month 24","definition_or_measurement_approach":"Total cumulative steroid dose from baseline to Day 60 and to Month 24."}
  • {"endpoint_text":"- Incidence of and time to cGvHD from Visit Day 60 until Visit Month 24","definition_or_measurement_approach":"Incidence and time-to-event analysis for chronic GvHD between Day 60 and Month 24."}
  • {"endpoint_text":"- Incidence of graft failure (GF) from baseline until Visit Month 24","definition_or_measurement_approach":"Incidence of graft failure from baseline through Month 24."}
  • {"endpoint_text":"- Incidence of and time to relapse or progression in subjects with underlying malignant disease from randomisation until Visit Month 24","definition_or_measurement_approach":"Incidence and time-to-relapse/progression in subjects with malignant disease from randomisation to Month 24."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomisation to event (GF, relapse/progression, or death) up to Month 24."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Same as above (duplicate entry in source)."}
  • {"endpoint_text":"- The incidence and severity of all adverse events (AEs) until Visit Day 60 or until 30 days after last administration of trial treatment, whichever is later. Thereafter, the incidence of adverse reactions (ARs) will be documented until Visit Month 24.","definition_or_measurement_approach":"Incidence and severity of AEs through Day 60 or 30 days after last treatment (whichever later); incidence of ARs documented through Month 24."}
  • {"endpoint_text":"- 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 in comparison to the baseline.","definition_or_measurement_approach":"Performance status (Karnofsky/Lansky) measured at specified visits versus baseline."}
  • {"endpoint_text":"- HRQoL measures: EuroQol 5D 5L (EQ 5D 5L) and the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACTBMT) at Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 in comparison to the baseline.","definition_or_measurement_approach":"HRQoL measured by EQ-5D-5L and FACT-BMT at specified visits vs baseline."}

Recruitment

Planned Sample Size
210
Recruitment Window Months
116
Consent Approach
Informed consent is required from subjects or parent(s)/legal guardian(s); informed assent form is required when applicable. Age-specific information and consent/assent forms are provided (including child/adolescent ICFs: Child 12-14, Child 15-17, Adolescent 15-17, parent ICFs). Multiple language versions of SIS/ICF documents are available in the submission (examples include Polish, Ukrainian, French, German, Russian, Turkish, Spanish, English). Consent/assent is handled according to national regulations.

Geography

Total Number Of Sites
37
Total Number Of Participants
210

Spain

Earliest CTIS Part Ii Submission Date
08-03-2024
Latest Decision Or Authorization Date
09-09-2025
Processing Time Days
550
Number Of Sites
8
Number Of Participants
30

Sites

Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Hematología/ Hematology
Contact Person Name
Javier López Jiménez
Contact Person Email
jlopezj.hrc@salud.madrid.org
Site Name
Hospital Germans Trias I Pujol
Department Name
Hematología/ Hematology
Contact Person Name
Anna Torrent Catarineu
Contact Person Email
atorrent@iconcologia.net
Site Name
Hospital Universitari Vall D Hebron
Department Name
Hematología/ Hematology
Contact Person Name
Maria Sola Soto
Contact Person Email
mariasola@vhio.net
Site Name
Hospital Universitario Regional De Malaga
Department Name
Hematología y Hemoterapia/ Hematology and Hemotherapy
Contact Person Name
María Jesús Pascual
Contact Person Email
mjcascon@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Clinical Haematology Service/ Servicio de hematología clínica
Contact Person Name
Alberto Mussetti
Contact Person Email
amussetti@iconcologia.net
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Hematología/ Hematology
Contact Person Name
Rafael Duarte
Contact Person Email
rduarte.work@gmail.com
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Hematología/ Hematology
Contact Person Name
Jaime Sanz Caballer
Contact Person Email
jaime.sanz@uv.es
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Hematología y Hemoterapia/ Hematology and Hemotherapy
Contact Person Name
Carlos Solano Vercet
Contact Person Email
carlos.solano@uv.es

Poland

Earliest CTIS Part Ii Submission Date
08-03-2024
Latest Decision Or Authorization Date
19-04-2024
Processing Time Days
42
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Transplantacji Szpiku i Onkohematologii
Contact Person Name
Sebastian Giebel
Contact Person Email
sebastian.giebel@io.gliwice.pl
Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Transplantacji SzpikuOnkologii i Hematologii Dziecięcej
Contact Person Name
Krzysztof Kalwak
Contact Person Email
krzysztof.kalwak@gmail.com

France

Earliest CTIS Part Ii Submission Date
08-03-2024
Latest Decision Or Authorization Date
12-09-2025
Processing Time Days
553
Number Of Sites
9
Number Of Participants
40

Sites

Site Name
CHU Besancon
Department Name
Service d Hematologie
Contact Person Name
Etienne DAGUINDAU
Contact Person Email
edaguindau@chu-besancon.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Service d Hematologie Clinique et Therapie Cellulaire
Contact Person Name
Amandine CHARBONNIER
Site Name
CHRU De Nancy
Department Name
Service d Hematologie
Contact Person Name
Maud D AVENI-PINEY
Contact Person Email
m.daveni-piney@chru-nancy.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Service des Maladies du Sang
Contact Person Name
Ibrahim YAKOUB-AGHA
Site Name
Centre Hospitalier Lyon Sud
Department Name
Service d Hematologie
Contact Person Name
Helene LABUSSIERE-WALLET
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Laboratoire d Hematologie
Contact Person Name
Martin CARRE
Contact Person Email
mcarre1@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Service d Hematologie
Contact Person Name
Michael LOSCHI
Contact Person Email
loschi.m@chu-nice.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service d Hematologie Clinique
Contact Person Name
Patrice CHEVALLIER
Site Name
Institut Universitaire Du Cancer Toulouse-Oncopole
Department Name
Service d Hematologie
Contact Person Name
Anne HUYNH
Contact Person Email
huynh.anne@iuct-oncopole.fr

Germany

Earliest CTIS Part Ii Submission Date
08-03-2024
Latest Decision Or Authorization Date
11-03-2026
Processing Time Days
733
Number Of Sites
18
Number Of Participants
130

Sites

Site Name
Universitaet Leipzig
Department Name
Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie
Contact Person Name
Georg-Nikolaus Franke
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Medizinische Klinik
Contact Person Name
Wolfgang Bethge
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
Contact Person Name
Matthias Eder
Contact Person Email
eder.matthias@mh-hannover.de
Site Name
Universitaetsklinikum Jena KöR
Department Name
Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische Onkologie
Contact Person Name
Inken Hilgendorf
Site Name
University Hospital Cologne AöR
Department Name
Klinik I für Innere Medizin
Contact Person Name
Udo Holtick
Contact Person Email
udo.holtick@uk-koeln.de
Site Name
Medical Center - University Of Freiburg
Department Name
Klinik für Innere Medizin I Klinik für Tumorbiologie Hämatologie, Onkologie und Stammzelltransplant
Contact Person Name
Robert Zeiser
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Innere Medizin II Hämatologie und Onkologie
Contact Person Name
Friedrich Stölzel
Contact Person Email
friedrich.stoelzel@uksh.de
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Universitätsklinikum Münster
Contact Person Name
Matthias Stelljes
Contact Person Email
stelljes@uni-muenster.de
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Medizinische Klinik und Poliklinik III
Contact Person Name
Martin Schumacher
Contact Person Email
martin.schumacher@ukbonn.de
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
III. Medizinische Klinik und Poliklinik Studienzentrale, Geb. 302, 2. OG
Contact Person Name
Eva-Maria Wagner-Drouet
Contact Person Email
eva.wagner@unimedizin-mainz.de
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Medizinische Klinik und Poliklinik II - Zentrum für Allogene Blutstammzelltransplantation
Contact Person Name
Sabrina Kraus
Contact Person Email
kraus_S3@ukw.de
Site Name
Universitaetsklinikum Mannheim GmbH
Department Name
III. Medizinische Klinik Hämatologie und Onkologie
Contact Person Name
Stefan Klein
Contact Person Email
stefan.klein@umm.de
Site Name
Universitaetsklinikum Frankfurt AöR
Department Name
Zentrum der Inneren Medizin: Medizinische Klinik II
Contact Person Name
Gesine Bug
Contact Person Email
gesine.bug@kgu.de
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Medizinische Klinik und Poliklinik 1
Contact Person Name
Désirée Kunadt
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie und Stammzelltransplantation KMT
Contact Person Name
Thomas Schroeder
Contact Person Email
Thomas.schroeder@uk-essen.de
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Klinik und Poliklinik für Innere Medizin III
Contact Person Name
Peter Herhaus
Contact Person Email
peter.herhaus@tum.de
Site Name
HELIOS Klinikum Berlin-Buch GmbH
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Contact Person Name
Judith Niederland
Site Name
Universitaetsklinikum Frankfurt AöR
Department Name
Klinik für Kinder- und Jugendmedizin
Contact Person Name
Peter Bader
Contact Person Email
peter.bader@kgu.de

Sponsor

Primary sponsor

Full Name
Medac Gesellschaft fuer klinische Spezialprapaerate mbH
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
Syneos Health Inc.
Responsibilities
Sponsor duties codes: 1,10,11,12,13,15 (TMF operations),2,5,6,8,9 (TMF operations explicitly listed)
Name
Medidata Solutions Inc.
Responsibilities
Sponsor duties codes: 3,7

Third parties

  • {"country":"France","full_name":"Novasco","duties_or_roles":"Patients' reimbursement","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"FACIT.Org Inc.","duties_or_roles":"Patient questionnaires","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Sponsor duties codes present in submission (codes: 1,10,11,12,13,15 (TMF operations),2,5,6,8,9); TMF operations","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"DRK Blutspendedienst Baden-Wuerttemberg-Hessen gGmbH","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties codes present (codes: 3,7)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Stichting EuroQol Research Foundation","duties_or_roles":"Patient questionnaires","organisation_type":"Patient organisation/association"}
  • {"country":"Germany","full_name":"Universitaetsklinikum Regensburg AöR","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
MC0518
Active Substance
MESENCHYMAL STROMAL CELLS, EX VIVO CULTURED
Modality
Cell therapy
Routes Of Administration
Intravenous use
Route
Intravenous
Orphan Designation
Yes
Maximum Dose
2000000 (unit: Other) - max daily dose amount
Investigational Product Name
EVEROLIMUS
Active Substance
EVEROLIMUS
Modality
Small molecule
Routes Of Administration
Oral use
Route
Oral
Maximum Dose
10 mg (max daily dose amount)
Investigational Product Name
MYCOPHENOLIC ACID
Active Substance
MYCOPHENOLATE MOFETIL / MYCOPHENOLIC ACID
Modality
Small molecule
Routes Of Administration
Oral use
Route
Oral
Maximum Dose
3 g (max daily dose amount for one product entry)
Investigational Product Name
ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)
Active Substance
MYCOPHENOLIC ACID (product entry labeling inconsistency present in source for ATG)
Modality
Other antibody
Routes Of Administration
Intravenous use
Route
Intravenous
Maximum Dose
5 mg/kg (max daily dose amount for product entry)

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