Clinical trial NCT06388564: A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease
Official title: A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Graft-versus-host-disease
Keywords: cGVHD
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2024-04-29
Enrollment: 120
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 determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with 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 1 allo-SCT (any type of stem cell donor, any conditioning regimen, and source of hematopoietic stem cells).
* Adequate hematologic function independent of platelet transfusion and growth factors for at least 7 days prior to study entry: ANC ≥ 0.75 × 109/L and platelet count ≥ 20 × 109/L.
* Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

* Received more than 1 prior allo-SCT. Prior autologous HCT is allowed.
* Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
* Received previous systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis.
* Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication.
* Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1.
* Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for the treatment of aGVHD are eligible only if they achieved a response (CR or PR) to JAK inhibitor treatment and did not discontinue due to toxicity.
* Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-SCT was performed, including DLIs for the treatment of molecular relapse.
* History of acute or chronic pancreatitis.
* History of thromboembolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) in the 6 months prior to study entry.
* Active symptomatic myositis.
* 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 end-stage renal disease on dialysis. Participants with CrCl of 30 to 59 mL/min on treatment with fluconazole are not eligible.
* 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.
* Currently active significant cardiac disease, such as uncontrolled arrhythmias, uncontrolled hypertension, or Class 3 or 4 congestive heart failure as defined by New York Heart Association, or a history of myocardial infarction or unstable angina within 6 months prior to randomization.
* Pregnant or breastfeeding.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: Objective Response Rate
timeFrame: 6 months
Secondary outcomes:
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years and 30 days
measure: Duration of Response
timeFrame: Up to 2 years
measure: Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score
timeFrame: Up to 2 years
measure: Best overall response in the first 6 months
timeFrame: Up to 6 months
measure: OR at 12 months, defined as CR or PR at 12 months (C14D1) in the absence of new systemic therapy for cGVHD.
timeFrame: 12 months
measure: Proportion of participants who remain corticosteroid-free
timeFrame: 4 weeks, 8 weeks and 6 months
measure: Organ-specific response in the first 6 cycles and on study, based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.
timeFrame: Up to 2 years
measure: Failure-free Survival (FFS)
timeFrame: Up to 2 years and 30 days
measure: Axatilimab pharmacokinetic (PK) in Plasma
timeFrame: Up to 2 years and 30 days
measure: Ruxolitinib PK in Plasma
timeFrame: Up to 2 years and 30 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California-Los Angeles Medl Cntr-Oncology Center Bowyer Clinic
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Center-Yale
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland-Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Fred and Pamela Buffett Cancer Center
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children'S Hospital
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert & the Medical College of Wisconsin
state: Wisconsin
city: Brugge
country: Belgium
facility: Az Sint-Jan Brugge - Oostende Av - Campus Sint-Jan
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis (Uz) Leuven
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire (Chu) de Liege
city: Roeselare
country: Belgium
facility: AZ DELTA
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Chu Sainte-Justine
state: Quebec
city: Vancouver
country: Canada
facility: Vancouver General Hospital
city: Frankfurt Am Main
country: Germany
facility: Klinikum Der Johann Wolfgang Goethe University
city: Freiburg I. Breisgau
country: Germany
facility: Universitatklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
city: Bologna
country: Italy
facility: Aou Policlinico S. Orsola-Malpighi
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore Policlinico Di Milano Uo Dermatologia
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesu Irccs
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Torino
country: Italy
facility: A.O.U. Citta Della Salute E Della Scienza Di Torino
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona Main
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Granvia DE L'hospitalet 199-203
country: Spain
facility: Ico Institut Catala D Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
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: 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
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital,
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals Nhs Foundation Trust
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Center
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: