NCT07124078招募中2 期
A Phase 2, Randomized, Open-Label Study of Axatilimab Versus Best Available Therapy in Pediatric Participants With Chronic Graft-Versus-Host Disease After at Least 2 Prior Lines of Systemic Therapy (AGAVE-256)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 85
- 主要终点
- Objective Response (OR) at 6 months
研究概览
简要总结
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.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 2 to < 18 years at the time of randomization.
- •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 C1D
- •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, ibrutinib, or pentostatin.
- •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.
排除标准
- •Receipt of more than 1 prior allo-HCT. Prior autologous HCT is allowed, including autologous CAR T-cell therapy given before the allo-SCT.
- •Documented evidence of relapse of the primary hematologic disease or receipt of treatment for relapse after allo-SCT, including DLI for treatment of any malignancy relapse, including molecular relapse. Autologous and allogeneic donor-derived CAR T-cell therapy after allo-SCT are not allowed. Note: Participants who received DLI solely for the management of mixed chimerism or as part of the planned transplant procedure and not for treatment of malignancy relapse (including molecular relapse), are eligible.
- •Systemic treatment with CNIs or mTOR inhibitors started within 2 weeks prior to C1D
- •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 or ALT > 3 × ULN or 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.
研究组 & 干预措施
Axatilimab
Experimental
Axatilimab at the protocol-defined dose.
干预措施: INCA034176 (Drug)
Best available Treatment (BAT)
Experimental
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.
干预措施: Best available Treatment (BAT) (Drug)
结局指标
主要结局
Objective Response (OR) at 6 months
时间窗: 6 months
Defined 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.
United States (US): Best overall Response (BOR)
时间窗: Up to 6 months
Defined as a best response of CR or PR in the first 6 months (up to and including Cycle 7 Day 1) in the absence of new systemic therapy for cGVHD.
次要结局
- Pharmacokinetics Parameter: AUC(0-t) of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: AUC 0-∞ of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: CL of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: Vz of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: t1/2 of axatilimab(Up to 5 years)
- Best Overall Response (BOR)(Up to 5 years)
- Overall Response at 12 months(12 months)
- Duration of Response (DOR) (in responders only)(Up to 5 years)
- Organ-specific response(Up to 5 years)
- Percent reduction in daily corticosteroid dose at 6 months(6 months)
- 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)
- Pharmacokinetics Parameter: Tmax of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: Cmin of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter (PK): Cmax of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: Tmax of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: Vz of axatilimab(Up to 5 years)
- Overall Response at 12 months(12 months)
- Pharmacokinetics Parameter: Cmin of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: AUC(0-t) of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: AUC 0-∞ of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: CL of axatilimab(Up to 5 years)
- Pharmacokinetics Parameter: t1/2 of axatilimab(Up to 5 years)
- Best Overall Response (BOR)(Up to 5 years)
- Duration of Response (DOR) (in responders only)(Up to 5 years)
- Organ-specific response(Up to 5 years)
- Percent reduction in daily corticosteroid dose at 6 months(6 months)
- 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)
- Best Overall Response (BOR) on study(Up to 5 years)
- BOR in the first 6 months(Up to 6 months)
- Overall Response (OR) at 12 months(12 months)
- US: OR at 6 months(6 months)
研究者
研究点 (85)
Loading locations...
相似试验
进行中（未招募）
1 期
A Ph1b/2 Study of Axatilimab Monotherapy in Chinese Participants With Recurrent or Refractory cGVHDNCT06843408Incyte Corporation32
进行中（未招募）
2 期
A Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host DiseaseChronic Graft-versus-host-diseaseNCT06388564Incyte Corporation130
招募中
3 期
A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host DiseaseChronic Graft-versus-host-diseaseNCT06585774Incyte Corporation240
招募中
1 期
Phase Ib Study of Axatilimab in Combination With Olaparib in BRCA1/2 and PALB2- Associated Metastatic HER2-negative Breast CancerPALB2-Mutated Breast CarcinomaHER2-negative Breast CancerBRCA1 MutationBRCA2 MutationBreast CancerNCT06488378Dana-Farber Cancer Institute20
招募中
2 期
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD)Chronic Graft-versus-host-diseaseNCT04710576Syndax Pharmaceuticals296