Clinical trial NCT06821542: A Study to Evaluate Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy
Official title: A Phase 3, Randomized, Open-Label Study of Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Graft-versus-host-disease
Keywords: cGVHD
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2025-02-12
Enrollment: 300
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be conducted to compare Axatilimab Versus Best Available Therapy in Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 12 years at the time of signing the ICF.
* Active, moderate to severe cGVHD, requiring systemic immune suppression.
* Participants with refractory or recurrent cGVHD who have received at least 2 lines of systemic therapy, including corticosteroids and ruxolitinib.
* Concomitant use of systemic corticosteroids is allowed. Participants on systemic corticosteroids must be on a stable dose of corticosteroids for at least 2 weeks prior to C1D1. Topical and inhaled corticosteroid agents are allowed.
* Participants must accept to be treated with one of the following BAT options on C1D1: CNI (cyclosporine or tacrolimus), ECP, MMF, an mTOR inhibitor (everolimus or sirolimus), rituximab, pentostatin, proteasome inhibitors, imatinib, or ibrutinib.
* History of allo-HCT from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative, nonmyeloablative, or reduced-intensity conditioning are eligible.

Exclusion Criteria:

* Receipt of more than 1 prior allo-HCT. Prior autologous HCT is allowed.
* Evidence of relapse of hematologic disease or treatment for relapse after the allo-SCT was performed, including DLI for the treatment of molecular relapse. Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
* Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
* Severe renal impairment, that is, estimated creatinine clearance \< 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or end-stage renal disease on dialysis.
* Impaired liver function, defined as total bilirubin \> 1.5 × ULN and/or ALT and AST \> 3 × ULN in participants with no evidence of liver cGVHD.
* History of acute or chronic pancreatitis.
* Active, symptomatic myositis.
* Pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: Objective Response (OR) at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Failure-free survival (FFS)
timeFrame: Up to 5 years
measure: Proportion of participants with a ≥ 7-point improvement in modified Lee Symptom Scale (mLSS) total score
timeFrame: Up to 5 years
measure: Overall Response at 12 months
timeFrame: 12 months
measure: Best Overall Response (BOR)
timeFrame: Up to 5 years
measure: DOR (in responders only)
timeFrame: Up to 5 years
measure: Organ-specific response
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Nonrelapse mortality (NRM)
timeFrame: Up to 5 years
measure: Time to primary hematologic disease relapse
timeFrame: Up to 5 years
measure: Percent reduction in daily corticosteroid dose at 6 months
timeFrame: 6 months
measure: Proportion of participants who tapered off all corticosteroids at 6 months
timeFrame: 6 months
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 5 years and 30 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck - Universitaetsklinik Fuer Innere Medizin Iii
city: Linz
country: Austria
facility: Krankenhaus Der Elisabethinen Linz Gmbh
city: Vienna
country: Austria
facility: St. Anna Childrens Hospital
city: Wien
country: Austria
facility: Medizinische Universitat Wien, Universitatsklinik Fur Innere Medizin I
city: Brugge
country: Belgium
facility: Az Sint-Jan Brugge Av
city: Brussels
country: Belgium
facility: Hopital Universitaire de Bruxelles (H.U.B)/ Academisch Ziekenhuis Brussel
city: Godinne-mont
country: Belgium
facility: Chu Ucl Namur Site Godinne
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Liege
country: Belgium
facility: Chu Liege -Centre Hospitalier Universitaire Sart Tilman
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta
city: Woluwe-saint-lambert
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Hradec Kralove
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Ostrava-poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Ustav Hematologie A Krevni Transfuze (Uhkt), the Institute of Hematology and Blood Transfusion (Ihbt
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Helsinki
country: Finland
facility: New Children'S Hospital, University of Helsinki and Helsinki University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Amiens
country: France
facility: Chu D'Amiens-Picardie - Hopital Sud
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque
city: Caen
country: France
facility: CHU CAEN
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire (Chru) de Lille - Hopital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Chu de Nantes
city: Nice Cedex 3
country: France
facility: Centre Hospitalier Universitaire de Nice,Hopital L Archet
city: Paris
country: France
facility: Hospital Saint-Louis - Aphp
city: Paris
country: France
facility: Hopital Universitaire Robert Debre
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Institut Claudius Regaud Cancer Comprehensive Center - Iuct Oncopole
city: Vandoeuvre-les-nancy
country: France
facility: Chru Nancy
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy-Gustave Roussy Cancer Center -Ditep
city: Aachen
country: Germany
facility: Uniklinik Rwth Aachen Medizinische Klinik Iv
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Frankfurt Am Main
country: Germany
facility: Klinikum Der Johann Wolfgang Goethe-Universitaet
city: Freiburg I. Breisgau
country: Germany
facility: Universitaetsklinikum Freiburg
city: Gottingen
country: Germany
facility: Universitaetsmedizin Goettingen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Homburg/saar
country: Germany
facility: Universitaetsklinikum Des Saarlandes
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein, Uksh-Campus Kiel
city: Koln
country: Germany
facility: Universitaetsklinikum Koeln
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Mainz
country: Germany
facility: Universitaetsmedizin Der Johannes - Gutenberg Universitaet Mainz
city: Marburg
country: Germany
facility: Klinikum Der Philipps-Universitaet Marburg
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Regensburg
country: Germany
facility: University Clinic Regensburg
city: ULM
country: Germany
facility: University Hospital of Ulm, Universitatsklinikum Ulm
city: Wurzburg
country: Germany
facility: University of Wuerzburg
city: Athens
country: Greece
facility: General Hospital of Athens Evangelismos - Eye Hospital
city: Athens
country: Greece
facility: Attikon Hospital and Cutaneous Lymphoma Clinic-Athens University Medical School
city: Patras
country: Greece
facility: University Hospital of Patras
city: Pilea Chortiatis
country: Greece
facility: General Hospital of Thessalonikis George Papanikolaou - Gene and Cell Therapy Center
city: Dublin 8
country: Ireland
facility: St. James Hospital
city: Alessandria
country: Italy
facility: Ss Antonio & Biagio and C. Arrigo Hospital
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Delle Marche Clinica Ematologica
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: Azienda Ospedaliera Sant'Orsola Malpighi
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S. Orsola-Malpighi - Istituto Di Ematolog
city: Brescia
country: Italy
facility: Universita Degli Studi Di Brescia - Azienda Ospedaliera Spedali Civili Di Brescia
city: Catania
country: Italy
facility: Azienda Policlinico Vittorio Emanuele, Presidio G Rodolico, Universita Di Catania
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
city: Genova
country: Italy
facility: Irccs - Azienda Ospedaliera Universitaria - Ist San Martino
city: Lecce
country: Italy
facility: Pia Fondazione Cardinale Giovanni Panico Azienda Ospedaliera
city: Milano
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) - Ospedale San Raffaele (Hsr) (Istituto
city: Milan
country: Italy
facility: Fondazione Irccs Ca' Granda - Ospedale Maggiore Policlinico
city: Milan
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo Di Monza
city: Naples
country: Italy
facility: Azienda Ospedaliero Universitaria Federico Ii Di Napoli
city: Napoli
country: Italy
facility: Azienda Ospedaliera Di Rilievo Nazionale (Aorn) 'Antonio Cardarelli'
city: Padova
country: Italy
facility: Azienda Ospedale Universita Di Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico San Matteo
city: Pescara
country: Italy
facility: Presidio Ospedaliero Spirito Santo Azienda U.S.L. Pescara
city: Reggio Calabria
country: Italy
facility: Morelli Hospital
city: Roma
country: Italy
facility: Aou Policlinico Umberto I
city: Roma
country: Italy
facility: A. Gemelli University Hospital, Catholic University of the Sacred Heart
city: Rome
country: Italy
facility: Fondazione Ptv Policlinico Tor Vergata
city: Rome
country: Italy
facility: Irccs Ospedale Pediatrico Bambino Gesu
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: San Giovanni Rotondo
country: Italy
facility: Fondazione Ircss Casa Sollievo Della Sofferenza
city: Torino
country: Italy
facility: A.O.U. Citta Della Salute E Della Scienza Di Torino
city: Treviso
country: Italy
facility: Ospedale Santa Maria Di Ca' Foncello
city: Udine
country: Italy
facility: Clinica Ematologica, Dism Azienda Ospedaliero Universitaria
city: Verona
country: Italy
facility: Uoc Ematologia E Centro Trapianti Midollo Osseo Br, Ospedale Borgo Roma
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center (Amsterdam Umc), Vrije University Medical Center (Vumc)
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center (Mumc)
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum 1
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht (Umc Utrecht)
city: ZA Leiden
country: Netherlands
facility: Leiden University Medical Center (Leids Universitair Medisch Centrum (Lumc))
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Rikshospitalet University Hospital
city: Lisboa
country: Portugal
facility: Ipo Lisboa Francisco Gentil
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario Lisboa Norte Epe
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E
city: Badalona
country: Spain
facility: Institut Catala D'Oncologia Badalona, Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (Hospital Clinic I Provincial)
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Institut Catala D Oncologia
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de La Arrixaca
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu Barcelona - Children'S Hospital
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrín
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon (Hgugm)
city: Madrid
country: Spain
facility: Hospital Universitario Infantil Nino Jesus
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: SAN Sebasttian
country: Spain
facility: Hospital Universitario de Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia (Instituto de Investigacion Sanitaria Incliva)
city: Valencia
country: Spain
facility: Universitat de Valencia - Hospital Universitari I Politecnic La Fe de Valencia (Hospital La Fe Bulev
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Gothenburg
country: Sweden
facility: University of Gothenburg and Queen Silvia Children S Hospital At Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus - Universitetssjukhuset I Lund
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Centrum For Cellterapi Och Allogen Stamcellstransplantation
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve (Hug) - Centre de Recherche Clinique (Crc)
city: Zurich
country: Switzerland
facility: Universitats- Kinderspital Zurich ¿ Eleonorenstiftung
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale Nhs Trust - University Hospital of Wales (Uhw)
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital - Nhs Greater Glasgow & Clyde - South Glasgow University Hospita
city: Leeds
country: United Kingdom
facility: St James'S University Hospital - Leeds Teaching Hospitals Nhs Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester Nhs Trust-Leicester Royal Infirmary
city: London
country: United Kingdom
facility: King'S College Hospital Nhs Foundation Trust
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: