A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease
- Conditions
- Chronic Graft-versus-host-disease
- Interventions
- Registration Number
- NCT06388564
- Lead Sponsor
- Incyte Corporation
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- ≥ 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Group A Axatilimab Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose. Treatment Group C Corticosteroids Corticosteroids alone will be administered at a protocol defined starting dose. Treatment Group A Ruxolitinib Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose. Treatment Group B Ruxolitinib Ruxolitinib will be administered at a protocol defined starting dose.
- Primary Outcome Measures
Name Time Method Objective Response Rate 6 months 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.
- Secondary Outcome Measures
Name Time Method Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score Up to 2 years Duration of Response Up to 2 years 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.
Proportion of participants who remain corticosteroid-free 4 weeks, 8 weeks and 6 months Axatilimab pharmacokinetic (PK) in Plasma Up to 2 years and 30 days Axatilimab concentration in plasma.
OR at 12 months, defined as CR or PR at 12 months (C14D1) in the absence of new systemic therapy for cGVHD. 12 months Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD
Best overall response in the first 6 months Up to 6 months Define as PR or CR in the first 6 months.
Failure-free Survival (FFS) Up to 2 years and 30 days 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.
Ruxolitinib PK in Plasma Up to 2 years and 30 days Ruxolitinib concentration in plasma.
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. Up to 2 years Based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD.
Number of participants with Treatment-emergent Adverse Events (TEAEs) Up to 2 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.
Trial Locations
- Locations (70)
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
University of California-Los Angeles Medl Cntr-Oncology Center Bowyer Clinic
🇺🇸Los Angeles, California, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Smilow Cancer Center-Yale
🇺🇸New Haven, Connecticut, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Scroll for more (60 remaining)Queen Elizabeth Hospital🇬🇧Birmingham, United Kingdom