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
- Conditions
- Chronic Graft-versus-host-disease
- Interventions
- Drug: INCA034176Drug: Best Available Therapy (BAT)
- Registration Number
- NCT06821542
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Axatilimab INCA034176 Axatilimab at the protocol-defined dose. Best available Treatment (BAT) Best Available Therapy (BAT) Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. Best available Treatment (BAT) Best Available Therapy (BAT) Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. Axatilimab INCA034176 Axatilimab at the protocol-defined dose.
- Primary Outcome Measures
Name Time Method Objective Response (OR) at 6 months 6 months Defined for each treatment group as complete response (CR) or partial response (PR) at 6 months (Cycle 7 Day 1, 28-day cycles) in the absence of new systemic therapy for cGVHD. Responses defined by the 2014 NIH consensus criteria.
- Secondary Outcome Measures
Name Time Method Failure-free survival (FFS) Up to 5 years Defined as the time from the date of randomization to the date of addition or initiation of another systemic therapy for cGVHD, relapse of underlying disease, or death due to any cause.
Proportion of participants with a ≥ 7-point improvement in modified Lee Symptom Scale (mLSS) total score Up to 5 years Overall Response at 12 months 12 months Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD.
Nonrelapse mortality (NRM) Up to 5 years Defined as the time from the date of randomization to the date of death not preceded by relapse of primary hematologic disease.
Best Overall Response (BOR) Up to 5 years Defined as the best response of CR or PR in the first 6 months (up to and including Cycle 7 Day 1), and at any timepoint up to the initiation of new therapy for cGVHD.
DOR (in responders only) Up to 5 years Defined as the time from the date of first response (PR or CR) to the date of progression of cGVHD from baseline scoring, start of new systemic treatment for cGVHD, or death from any cause, whichever comes first. An additional measure of response durability will consider DOR as the time from the date of first response to the date of new systemic therapy for cGVHD or death from any cause, whichever occurs first.
Organ-specific response Up to 5 years Organ-specific response as defined in the protocol.
Overall Survival (OS) Up to 5 years Defined as the time from the date of randomization to the date of death due to any cause.
Time to primary hematologic disease relapse Up to 5 years Defined as the time from the date of randomization to the date of relapse.
Percent reduction in daily corticosteroid dose at 6 months 6 months Proportion of participants who tapered off all corticosteroids at 6 months 6 months Number of participants with Treatment-emergent Adverse Events (TEAEs) Up to 5 years and 30 days Defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
Related Research Topics
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Trial Locations
- Locations (131)
Aou Policlinico Umberto I
🇮🇹Roma, Italy
Medical University of Graz
🇦🇹Graz, Austria
Medizinische Universitaet Innsbruck - Universitaetsklinik Fuer Innere Medizin Iii
🇦🇹Innsbruck, Austria
Krankenhaus Der Elisabethinen Linz Gmbh
🇦🇹Linz, Austria
St. Anna Childrens Hospital
🇦🇹Vienna, Austria
Medizinische Universitat Wien, Universitatsklinik Fur Innere Medizin I
🇦🇹Wien, Austria
Az Sint-Jan Brugge
🇧🇪Brugge, Belgium
Hopital Universitaire de Bruxelles (H.U.B)/ Academisch Ziekenhuis Brussel
🇧🇪Brussels, Belgium
Chu Ucl Namur Site Godinne
🇧🇪Godinne-mont, Belgium
Universitair Ziekenhuis (Uz) Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liege - Sart Tilman
🇧🇪Liege, Belgium
Algemeen Ziekenhuis Delta
🇧🇪Roeselare, Belgium
Cliniques Universitaires Ucl Saint-Luc
🇧🇪Woluwe-saint-lambert, Belgium
Fakultni Nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni Nemocnice Ostrava (Fno)
🇨🇿Ostrava-poruba, Czechia
Ustav Hematologie A Krevni Transfuze (Uhkt), the Institute of Hematology and Blood Transfusion (Ihbt
🇨🇿Praha 2, Czechia
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
New Children'S Hospital, University of Helsinki and Helsinki University Hospital
🇫🇮Helsinki, Finland
Turku University Hospital
🇫🇮Turku, Finland
Chu D'Amiens-Picardie - Hopital Sud
🇫🇷Amiens, France
Centre Hospitalier Universitaire de Bordeaux - Hopital Haut-Leveque
🇫🇷Bordeaux, France
CHU CAEN
🇫🇷Caen, France
Centre Hospitalier Regional Universitaire (Chru) de Lille - Hopital Claude Huriez
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Chu de Nantes
🇫🇷Nantes, France
Centre Hospitalier Universitaire de Nice,Hopital L Archet
🇫🇷Nice Cedex 3, France
Hospital Saint-Louis - Aphp
🇫🇷Paris, France
Hopital Universitaire Robert Debre
🇫🇷Paris, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite Cedex, France
Centre Henri Becquerel
🇫🇷Rouen, France
Institut Claudius Regaud Cancer Comprehensive Center - Iuct Oncopole
🇫🇷Toulouse, France
Chru Nancy
🇫🇷Vandoeuvre-les-nancy, France
Institut Gustave Roussy-Gustave Roussy Cancer Center -Ditep
🇫🇷Villejuif Cedex, France
Uniklinik Rwth Aachen Medizinische Klinik Iv
🇩🇪Aachen, Germany
Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
University Hospital Carl Gustav Carus
🇩🇪Dresden, Germany
Universitatsklinikum Erlangen
🇩🇪Erlangen, Germany
Klinikum Der Johann Wolfgang Goethe-Universitaet
🇩🇪Frankfurt Am Main, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg I. Breisgau, Germany
Universitaetsmedizin Goettingen
🇩🇪Gottingen, Germany
Universitaetsklinikum Halle
🇩🇪Halle, Germany
Universitaetsklinikum Des Saarlandes
🇩🇪Homburg/saar, Germany
Universitaetsklinikum Schleswig-Holstein, Uksh-Campus Kiel
🇩🇪Kiel, Germany
Universitaetsklinikum Koeln
🇩🇪Koln, Germany
University Hospital Leipzig
🇩🇪Leipzig, Germany
Universitaetsmedizin Der Johannes - Gutenberg Universitaet Mainz
🇩🇪Mainz, Germany
Klinikum Der Philipps-Universitaet Marburg
🇩🇪Marburg, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
University Clinic Regensburg
🇩🇪Regensburg, Germany
University Hospital of Ulm, Universitatsklinikum Ulm
🇩🇪ULM, Germany
University of Wuerzburg
🇩🇪Wurzburg, Germany
General Hospital of Athens Evangelismos - Eye Hospital
🇬🇷Athens, Greece
Attikon Hospital and Cutaneous Lymphoma Clinic-Athens University Medical School
🇬🇷Athens, Greece
University Hospital of Patras
🇬🇷Patras, Greece
General Hospital of Thessalonikis George Papanikolaou - Gene and Cell Therapy Center
🇬🇷Pilea Chortiatis, Greece
St. James Hospital
🇮🇪Dublin 8, Ireland
Ss Antonio & Biagio and C. Arrigo Hospital
🇮🇹Alessandria, Italy
Azienda Ospedaliero Universitaria Delle Marche Clinica Ematologica
🇮🇹Ancona, Italy
Azienda Ospedaliera Papa Giovanni Xxiii
🇮🇹Bergamo, Italy
Aou Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S. Orsola-Malpighi - Istituto Di Ematolog
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Azienda Policlinico Vittorio Emanuele, Presidio G Rodolico, Universita Di Catania
🇮🇹Catania, Italy
Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
🇮🇹Firenze, Italy
Irccs - Azienda Ospedaliera Universitaria - Ist San Martino
🇮🇹Genova, Italy
Pia Fondazione Cardinale Giovanni Panico Azienda Ospedaliera
🇮🇹Lecce, Italy
Ospedale San Raffaele Irccs
🇮🇹Milano, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore
🇮🇹Milan, Italy
Azienda Ospedaliera Niguarda Ca Granda
🇮🇹Milan, Italy
Azienda Ospedaliera San Gerardo Di Monza
🇮🇹Monza, Italy
Azienda Ospedaliera Universitaria Federico Ii
🇮🇹Naples, Italy
Azienda Ospedaliera Di Rilievo Nazionale (Aorn) 'Antonio Cardarelli'
🇮🇹Napoli, Italy
Azienda Ospedale Universita Di Padova
🇮🇹Padova, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
🇮🇹Palermo, Italy
Irccs Fondazione Policlinico San Matteo
🇮🇹Pavia, Italy
Presidio Ospedaliero Ospedale Civile Spirito Santo
🇮🇹Pescara, Italy
Morelli Hospital
🇮🇹Reggio Calabria, Italy
A. Gemelli University Hospital, Catholic University of the Sacred Heart
🇮🇹Roma, Italy
Fondazione Ptv Policlinico Tor Vergata
🇮🇹Rome, Italy
Irccs Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Fondazione Ircss Casa Sollievo Della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
A.O.U. Citta Della Salute E Della Scienza Di Torino
🇮🇹Torino, Italy
Ospedale Santa Maria Di Ca' Foncello
🇮🇹Treviso, Italy
Clinica Ematologica, Dism Azienda Ospedaliero Universitaria
🇮🇹Udine, Italy
Uoc Ematologia E Centro Trapianti Midollo Osseo Br, Ospedale Borgo Roma
🇮🇹Verona, Italy
Amsterdam University Medical Center (Amsterdam Umc), Vrije University Medical Center (Vumc)
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Maastricht University Medical Center (Mumc)
🇳🇱Maastricht, Netherlands
Erasmus Medisch Centrum 1
🇳🇱Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht (Umc Utrecht)
🇳🇱Utrecht, Netherlands
Leiden University Medical Center (Leids Universitair Medisch Centrum (Lumc))
🇳🇱ZA Leiden, Netherlands
Haukeland University Hospital
🇳🇴Bergen, Norway
Rikshospitalet University Hospital
🇳🇴Oslo, Norway
Ipo Lisboa Francisco Gentil
🇵🇹Lisboa, Portugal
Centro Hospitalar Universitario Lisboa Norte Epe
🇵🇹Lisboa, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E
🇵🇹Porto, Portugal
Hospital Universitari Germans Trias I Pujol
🇪🇸Badalona, Spain
Hospital Universitario Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona (Hospital Clinic I Provincial)
🇪🇸Barcelona, Spain
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Institut Catala D Oncologia
🇪🇸Barcelona, Spain
Hospital Clinico Universitario Virgen de La Arrixaca
🇪🇸El Palmar, Spain
Hospital Sant Joan de Deu Barcelona - Children'S Hospital
🇪🇸Esplugues de Llobregat, Spain
Hospital Universitario Virgen de Las Nieves
🇪🇸Granada, Spain
Hospital Universitario de Gran Canaria Doctor Negrín
🇪🇸Las Palmas de Gran Canaria, Spain
Hospital General Universitario Gregorio Maranon (Hgugm)
🇪🇸Madrid, Spain
Hospital Infantil Unversitario Nino Jesus
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Donostia
🇪🇸SAN Sebasttian, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia (Instituto de Investigacion Sanitaria Incliva)
🇪🇸Valencia, Spain
Universitat de Valencia - Hospital Universitari I Politecnic La Fe de Valencia (Hospital La Fe Bulev
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Sahlgrenska University Hospital
🇸🇪Goteborg, Sweden
University of Gothenburg and Queen Silvia Children S Hospital At Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Skanes Universitetssjukhus - Universitetssjukhuset I Lund
🇸🇪Lund, Sweden
Karolinska Universitetssjukhuset, Centrum For Cellterapi Och Allogen Stamcellstransplantation
🇸🇪Stockholm, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden
University Hospital Basel
🇨🇭Basel, Switzerland
Hopitaux Universitaires de Geneve (Hug) - Centre de Recherche Clinique (Crc)
🇨🇭Geneva, Switzerland
Universitats- Kinderspital Zurich ¿ Eleonorenstiftung
🇨🇭Zurich, Switzerland
Cardiff and Vale Nhs Trust - University Hospital of Wales (Uhw)
🇬🇧Cardiff, United Kingdom
Queen Elizabeth University Hospital - Nhs Greater Glasgow & Clyde - South Glasgow University Hospita
🇬🇧Glasgow, United Kingdom
Leeds Teaching Hospital
🇬🇧Leeds, United Kingdom
University Hospitals of Leicester Nhs Trust-Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
King'S College Hospital Nhs Foundation Trust
🇬🇧London, United Kingdom