Chronic Graft-versus-host-disease
Conditions
Keywords
cGVHD
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).
Interventions
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Percent reduction in daily corticosteroid dose | 6 months | — |
| 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 | — |
Countries
Australia, Austria, Canada, Denmark, France, Germany, Ireland, Italy, Japan, Netherlands, Spain, United Kingdom, United States
Contacts
CONTACTIncyte Corporation Call Center (US)
CONTACTIncyte Corporation Call Center (ex-US)
STUDY_DIRECTORAlbert Assad, MD
Incyte Corporation
Outcome results
None listed