Clinical trial NCT06585774: A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
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: 2024-09-19
Enrollment: 240
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 the efficacy of axatilimab versus placebo in combination with corticosteroids as initial treatment for moderate or severe chronic graft-versus-host disease (cGVHD).


Eligibility criteria: Inclusion Criteria:

* ≥ 12 years of age at the time of informed consent.
* New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy.
* 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.
* Adequate hematologic function with ANC ≥ 0.5 × 109/L independent of growth factors for at least 7 days prior to study entry.
* Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

* Received more than 1 prior allo-HCT. Prior autologous HCT is allowed.
* Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
* Received more than 7 days of systemic corticosteroid treatment for cGVHD or unable to begin a prednisone dose ≥ 1.0 mg/kg per day (or methylprednisolone equivalent) for cGVHD.
* Received previous systemic treatment for cGVHD, including extracorporeal photopheresis.
* Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D1.
* Prior treatment with CSF-1R targeted therapies.
* Active, uncontrolled bacterial, fungal, parasitic, or viral infection.
* Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-HCT was performed, including DLIs for the treatment of molecular relapse.
* History of acute or chronic pancreatitis.
* Active symptomatic myositis.
* History or current diagnosis of cardiac disease indicating significant risk of safety for participation in the study, such as uncontrolled or significant cardiac disease.
* Severe renal impairment, that is, estimated CrCl \< 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or endstage 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.
* Pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: Event Free Survival (EFS)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: 6 months
measure: Event Free Survival 2
timeFrame: Up to 3 years
measure: Proportion of participants with a ≥ 7-point improvement in mLSS total score
timeFrame: Up to 3 years
measure: Overall Response
timeFrame: 12 Months
measure: DOR (in responders only)
timeFrame: Up to 3 years
measure: Best Overall Response (BOR)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Nonrelapse mortality (NRM)
timeFrame: Up to 3 years
measure: Failure-free survival (FFS)
timeFrame: Up to 3 years
measure: Relapse of hematologic diseases
timeFrame: Up to 3 years
measure: Time to primary hematologic disease relapse
timeFrame: Up to 3 years
measure: Percent reduction in daily corticosteroid dose
timeFrame: 6 months
measure: Proportion of participants who tapered off all corticosteroids
timeFrame: 6 months
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 3 years and 30 days
measure: Change from baseline in circulating monocyte number and phenotype (CD14/16)
timeFrame: Up to 3 years and 30 days
measure: Change from baseline in soluble markers for bone resorption and formation, including bone-specific alkaline phosphatase (BAP) and C-terminal telopeptide (CTX)
timeFrame: Up to 3 years and 30 days
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Medical Center, Moores Cancer Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Orlando
country: United States
facility: Orlando Health Cancer Institute Downtown Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Hematology Oncology
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of Nj
state: New Jersey
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Salt Lake City
country: United States
facility: Intermountain Blood and Marrow Transplant
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute
state: West Virginia
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health Medical Oncology and Clinical Haematology
state: Victoria
city: Innsbruck
country: Austria
facility: Innsbruck University Hospital
city: Linz Cet
country: Austria
facility: Ordensklinikum Linz Gmbh Elisabethinen
city: Wien
country: Austria
facility: St. Anna Childrens Hospital
city: Calgary
country: Canada
facility: Alberta'S Children Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Vancouver
country: Canada
facility: Vancouver General Hospital
city: Amiens Cedex 1
country: France
facility: Chu Amiens Picardie - Hopital Sud
city: Nancy
country: France
facility: Hopitaux de Brabois
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
city: Nice Cedex 3
country: France
facility: Chu de Nice - Hospital L Archet
city: Paris
country: France
facility: Hospital Saint Louis
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon Centre Hospitalier Lyon Sud
city: Aachen
country: Germany
facility: University Medical Center Rwth Aachen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn, University Hospital Bonn
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus Technical University Dresden
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Halle
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
city: Dublin 8
country: Ireland
facility: St. James Hospital
city: Alessandria
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Alessandria Ss.Antonio E Biagio E Cesare Arrigo
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Delle Marche
city: Napoli
country: Italy
facility: Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesu Irccs
city: San Giovanni Rotondo
country: Italy
facility: I.R.C.C.S. Casa Sollievo Della Sofferenza
city: Tricase
country: Italy
facility: Azienda Ospedaliera Card. G. Panico
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona
city: Aichi-ken
country: Japan
facility: Anjo Kosei Hospital
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
city: Hyogo
country: Japan
facility: Kobe City Medical Center General Hospital
city: Isehara Kanagawa
country: Japan
facility: Tokai University Hospital
city: Kumamoto Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Maebashi
country: Japan
facility: Gunma Saiseikai Maebashi Hospital
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Okayama-ken
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Sapporo Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: London
country: United Kingdom
facility: University College London Hospitals (Uclh)
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals Nhs Trust
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, MD
role: STUDY_DIRECTOR
References: