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)
Universitat de Valencia - Hospital Universitari I Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
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 Av
🇧🇪Brugge, Belgium
Hopital Universitaire de Bruxelles (H.U.B)/ Academisch Ziekenhuis Brussel
🇧🇪Brussels, Belgium
Chu Ucl Namur Site Godinne
🇧🇪Godinne-mont, Belgium
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