NCT06388564进行中（未招募）2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 130
- 试验地点
- 129
- 主要终点
- Objective Response Rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 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.
排除标准
- •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 C1D
- •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.
研究组 & 干预措施
Treatment Group C
Experimental
Corticosteroids alone will be administered at a protocol defined starting dose.
干预措施: Corticosteroids (Drug)
Treatment Group A
Experimental
Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose.
干预措施: Axatilimab (Drug)
Treatment Group A
Experimental
Axatilimab will be administered at a protocol defined starting dose plus ruxolitinib at a protocol defined starting dose.
干预措施: Ruxolitinib (Drug)
Treatment Group B
Experimental
Ruxolitinib will be administered at a protocol defined starting dose.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 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.
次要结局
- Best overall response in the first 6 months(Up to 6 months)
- Duration of Response(Up to 2 years)
- 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)
- Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score(Up to 2 years)
- OR at 12 months, defined as CR or PR at 12 months (C14D1) in the absence of new systemic therapy for cGVHD.(12 months)
- Failure-free Survival (FFS)(Up to 2 years and 30 days)
- Ruxolitinib PK in Plasma(Up to 2 years and 30 days)
- 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)
- Number of participants with Treatment-emergent Adverse Events (TEAEs)(Up to 2 years and 30 days)
研究者
研究点 (129)
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