A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease

Chronic Graft-versus-host-disease Clinical Trial

Official title:

A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06388564
• Other study ID #: INCA34176-254
• Secondary ID: 2022-502168-19-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 8, 2024
• Est. completion date: September 5, 2028

Study information

• Verified date: April 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be conducted to determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: September 5, 2028
• Est. primary completion date: March 5, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 1 allo-SCT (any type of stem cell donor, any conditioning regimen, and source of hematopoietic stem cells).
• Adequate hematologic function independent of platelet transfusion and growth factors for at least 7 days prior to study entry: ANC = 0.75 × 109/L and platelet count = 20 × 109/L.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Received more than 1 prior allo-SCT. Prior autologous HCT is allowed.
• Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
• Received previous systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis.
• Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication.
• Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1.
• Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for the treatment of aGVHD are eligible only if they achieved a response (CR or PR) to JAK inhibitor treatment and did not discontinue due to toxicity.
• Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-SCT was performed, including DLIs for the treatment of molecular relapse.
• History of acute or chronic pancreatitis.
• History of thromboembolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) in the 6 months prior to study entry.
• Active symptomatic myositis.
• 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 end-stage renal disease on dialysis. Participants with CrCl of 30 to 59 mL/min on treatment with fluconazole are not eligible.
• 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.
• Currently active significant cardiac disease, such as uncontrolled arrhythmias, uncontrolled hypertension, or Class 3 or 4 congestive heart failure as defined by New York Heart Association, or a history of myocardial infarction or unstable angina within 6 months prior to randomization.
• Pregnant or breastfeeding. Other protocol-defined Inclusion/Exclusion Criteria may apply.

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft-versus-host-disease
• Graft vs Host Disease

Intervention

Drug:
• Axatilimab
Axatilimab will be administered at protocol defined dose.
• Ruxolitinib
Ruxolitinib will be administered at protocol defined dose.
• Corticosteroids
Corticosteroids will be administered at protocol defined dose.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Defined as Complete Response (CR) or Partial Response (PR) at 6 months in the absence of new systemic therapy for cGVHD. Response assessment will be based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	6 months
Secondary	Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment.	Up to 2 years and 30 days
Secondary	Duration of Response	Defined as the time from the first response (PR or CR) to the date of progression of cGVHD, start of new systemic therapy or death from any cause.	Up to 2 years
Secondary	Proportion of participants with a = 7-point improvement in modified Lee symptom scale (mLSS) score		Up to 2 years
Secondary	Best overall response in the first 6 months	Define as PR or CR in the first 6 months.	Up to 6 months
Secondary	OR at 12 months, defined as CR or PR at 12 months (C14D1) in the absence of new systemic therapy for cGVHD.	Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD	12 months
Secondary	Proportion of participants who remain corticosteroid-free		4 weeks, 8 weeks and 6 months
Secondary	Organ-specific response in the first 6 cycles and on study, based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	Based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.	Up to 2 years
Secondary	Failure-free Survival (FFS)	Defined as the time from date of randomization to date of initiation of a new cGVHD treatment, malignancy relapse, or death due to any cause.	Up to 2 years and 30 days
Secondary	Axatilimab pharmacokinetic (PK) in Plasma	Axatilimab concentration in plasma.	Up to 2 years and 30 days
Secondary	Ruxolitinib PK in Plasma	Ruxolitinib concentration in plasma.	Up to 2 years and 30 days