A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
- Conditions
- Chronic Graft-versus-host-disease
- Interventions
- Registration Number
- NCT06585774
- Lead Sponsor
- Incyte Corporation
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
- ≥ 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Axatilimab + Corticosteroids INCA034176 Axatilimab and Corticosteroids at the protocol-defined dose. Axatilimab + Corticosteroids Corticosteroids Axatilimab and Corticosteroids at the protocol-defined dose. Placebo + Corticosteroids Placebo Matching placebo and Corticosteroids at the protocol-defined dose. Placebo + Corticosteroids Corticosteroids Matching placebo and Corticosteroids at the protocol-defined dose.
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) Up to 3 years Defined from the date of randomization to the date of any predefined event, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Objective Response (OR) 6 months Defined for each treatment group as CR or PR at 6 months Cycle 7 (28-day cycles), Day 1, in the absence of new systemic therapy for cGVHD. Responses defined by the 2014 NIH consensus criteria.
Event Free Survival 2 Up to 3 years Defined from the date of randomization to the date of any predefined event, whichever occurs first.
Proportion of participants with a ≥ 7-point improvement in mLSS total score Up to 3 years Overall Response 12 Months Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD.
DOR (in responders only) Up to 3 years Defined as the time from the date of first response (PR or CR) to the date of progression of cGVHD from nadir in any organ, start of new systemic treatment for cGVHD, or death from any cause, whichever comes first.
Overall Survival (OS) Up to 3 years Defined as the time from the date of randomization to the date of death due to any cause.
Nonrelapse mortality (NRM) Up to 3 years Defined as the time from the date of randomization to the date of death in the absence of primary hematologic disease relapse.
Failure-free survival (FFS) Up to 3 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.
Relapse of hematologic diseases Up to 3 years Defined as the reappearance of symptoms of underlying disease.
Time to primary hematologic disease relapse Up to 3 years Defined as the time from the date of randomization to the date of relapse.
Proportion of participants who tapered off all corticosteroids 6 months Number of participants with Treatment-emergent Adverse Events (TEAEs) Up to 3 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.
Change from baseline in circulating monocyte number and phenotype (CD14/16) Up to 3 years and 30 days Change from baseline in soluble markers for bone resorption and formation, including bone-specific alkaline phosphatase (BAP) and C-terminal telopeptide (CTX) Up to 3 years and 30 days Best Overall Response (BOR) Up to 3 years Defined as the best response of CR or PR at any timepoint up to the initiation of new therapy for cGVHD.
Percent reduction in daily corticosteroid dose 6 months
Trial Locations
- Locations (88)
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
🇩🇪Mainz, Germany
Klinikum Der Philipps-Universitaet Marburg
🇩🇪Marburg, Germany
University of California San Diego Medical Center, Moores Cancer Center
🇺🇸La Jolla, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Childrens National Hospital
🇺🇸Washington, District of Columbia, United States
Orlando Health Cancer Institute Downtown Orlando
🇺🇸Orlando, Florida, United States
Memorial Cancer Institute
🇺🇸Pembroke Pines, Florida, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
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