A Study to Evaluate Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy
- Conditions
- Chronic Graft-versus-host-disease
- Interventions
- Drug: Best available Treatment (BAT)
- Registration Number
- NCT07124078
- Lead Sponsor
- Incyte Corporation
- Brief Summary
This study will be conducted to compare Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft Versus Host Disease After at Least 2 Prior Lines of Systemic Therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Aged ≥ 2 to < 18 years at the time of signing the informed consent.
- 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, imatinib, methotrexate, 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, GFR < 30 mL/min/1.73 m2 as estimated using modified Schwartz formula, 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.
- Female adolescent participants who are 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 Treatment (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.
- 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 Pharmacokinetics Parameter (PK): Cmax of axatilimab Up to 5 years Defined as maximum observed plasma concentration of axatilimab.
Pharmacokinetics Parameter: Tmax of axatilimab Up to 5 years Defined as the time to reach the maximum plasma concentration of axatilimab.
Pharmacokinetics Parameter: Vz of axatilimab Up to 5 years Defined as the apparent oral dose volume of distribution of axatilimab.
Overall Response at 12 months 12 months Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD.
Pharmacokinetics Parameter: Cmin of axatilimab Up to 5 years Defined as the minimum observed plasma concentration of axatilimab.
Pharmacokinetics Parameter: AUC(0-t) of axatilimab Up to 5 years Defined as the area under the concentration-time curve up to the last measurable concentration of axatilimab.
Pharmacokinetics Parameter: AUC 0-∞ of axatilimab Up to 5 years Defined as the area under the concentration-time curve from 0 to infinity of axatilimab.
Pharmacokinetics Parameter: CL of axatilimab Up to 5 years Defined as the apparent oral dose clearance of axatilimab.
Pharmacokinetics Parameter: t1/2 of axatilimab Up to 5 years Defined as the apparent terminal phase disposition half-life of axatilimab.
Best Overall Response (BOR) Up to 5 years Defined as 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 systemic therapy for cGVHD.
Duration of Response (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, initiation 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.
Percent reduction in daily corticosteroid dose at 6 months 6 months Defined as Percent reduction in daily corticosteroid dose at Cycle 7 Day 1, and participants successfully tapered off all corticosteroids at Cycle 7 Day 1.
Changes in parameters collected using the pediatric stem cell quality of life (Q0L) questionnaire (PedsQL Stem Cell Transplant Module) Up to 5 years 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.