Chronic Graft-versus-host-disease
Conditions
Keywords
cGVHD
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.
Interventions
DRUGINCA034176
Axatilimab at the protocol-defined dose.
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.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: Vz of axatilimab | Up to 5 years | Defined as the apparent oral dose volume of distribution 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. |
| Overall Response at 12 months | 12 months | Defined as CR or PR at 12 months in the absence 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. |
Countries
Belgium, Germany, Italy, Spain, United Kingdom, United States
Contacts
CONTACTIncyte Corporation Call Center (US)
CONTACTIncyte Corporation Call Center (ex-US)
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed