A Study on the Safety and Efficacy of Gecacitinib in Patients With Chronic Graft-versus-Host Disease (cGVHD) Who Have Received Prior Treatment With Two or More Systemic Therapies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) at Week 24
研究概览
简要总结
Chronic Graft-versus-Host Disease (cGVHD) is a common late complication following allogeneic hematopoietic stem cell transplantation and a leading non-relapse cause of death. It is often treatment-refractory, significantly affecting patients' quality of life and prognosis. This study will evaluate the feasibility, safety, and tolerability of gecacitinib, a novel JAK and ACVR1 inhibitor, in 24 patients with moderate-to-severe cGVHD who have undergone two or more prior therapies. Participants will receive gecacitinib hydrochloride tablets for at least 24 weeks. Patients demonstrating disease stability, as assessed by the investigator, may continue treatment with the study drug until week 60, unless intolerability, disease progression, or initiation of new systemic therapy, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily Signed informed consent and aged ≥18 years
- •Undergone nonmyeloablative, myeloablative, or reduced-intensity allo-HSCT using bone marrow, peripheral blood stem cells, or umbilical cord blood from any donor source
- •Confirmed myeloid and platelet engraftment: ANC >1.0×10⁹/L and platelet count >25×10⁹/L; no hematopoietic growth factors or blood product transfusions within 7 days before screening
- •Clinically diagnosed moderate-to-severe cGVHD according to the 2014 NIH
- •Received 2-5 prior systemic cGVHD therapies with persistent disease
- •ECOG PS score of 0-2
- •Able to swallow tablets
- •Concomitant use of non-interacting immunosuppressants permitted
排除标准
- •Recurrence of malignancy or loss of full donor chimerism
- •Concurrent use of other JAK inhibitors, mesenchymal stem cells, or belumosudil (Eligible if discontinued for >8 weeks post-aGVHD treatment or stopped JAK inhibitors for cGVHD due to side effects.)
- •Severe pulmonary cGVHD (FEV1 ≤39% or NIH lung symptom score of 3)
- •Post-transplant lymphoproliferative disease
- •Significant abnormalities affecting safety assessment, such as uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) despite ≤2 antihypertensives; ALT/AST >3×ULN; DBIL/TBIL >1.5×ULN; serum creatinine >1.5×ULN
- •History of major cardiovascular events within 6 months.
- •Arrhythmia requiring treatment at screening
- •Gastrointestinal conditions impairing drug absorption
- •Surgery within 4 weeks of screening with incomplete recovery
- •Active/uncontrolled infections (viral, bacterial, parasitic, fungal) requiring treatment
- •Active tuberculosis within 6 months
- •Epilepsy or use of psychotropic/sedative drugs
- •Pregnant/breastfeeding or unwilling to use contraception during and 4 weeks post-study
- •Malignancy within 5 years (except the indication for transplant)
- •Use of anticoagulants/platelet inhibitors (except low-molecular-weight heparin)
- •Herbal medicine use within 1 week prior to enrollment
- •Hypersensitivity to gecacitinib or its components
- •Participation in another clinical trial within 4 weeks (or 5 half-lives of the previous study drug, whichever is longer)
- •Deemed unsuitable by the investigator
研究组 & 干预措施
Gecacitinib
干预措施: Gecacitinib Hydrochloride Tablets (Drug)
结局指标
主要结局
Overall Response Rate (ORR) at Week 24
时间窗: Week 24
ORR was defined as the proportion of patients achieving complete response (CR) or partial response (PR) without requiring additional systemic therapy for cGVHD.
次要结局
- ORR at Week 12, 48 and 60(week 12, 48 and 60)
- Overall Survival (OS)(Up to 24 months)
- Failure-free Survival (FFS)(Up to 24 months)
- Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose for ≥4 Weeks(Up to Day 180)
- Change From Baseline in Lee cGVHD Symptom Scale Scores(Through study completion, an average of 24 months)
- Best Overall Response (BOR)(Up to week 24)
- Duration of Response (DOR)(Up to 24 months)
- Relapse Rate(Up to 24 months)
- Change from Baseline in FACT-BMT(Through study completion, an average of 24 months)
- Change from Baseline in EQ-5D-5L(Through study completion, an average of 24 months)
- Adverse Events (AEs) and Adverse Drug Reactions (ADRs)(Up to 28 days after the last dose)
研究者
Yujun DONG
Director of the Hematology Department
Peking University First Hospital