Safety and Efficacy of Baricitinib in Thrombopoietin-Receptor-Agonist-Refractory Persistent Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplantation: A Phase Ib/II Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Adverse events in the Ib part
研究概览
简要总结
This is a prospective, open-label phase 1b/2 clinical trial to explore the safety and efficacy profiles of baricitinib in patients with thrombopoietin-receptor-agonist-refractory persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation.
详细描述
Phase 1 part:
The phase 1b part will use a standard 3+3 design to explore the safety profiles and to establish the recommended phase 2 dose (RP2D) of baricitinib. The initial dose is 2 mg once daily, and the maximum dose is 4 mg once daily. Additional patients may be enrolled to further explore a selected dose defined by dose escalation cohorts (up to 9 patients in each dose level).
Phase 2 part:
The phase 2 part is a single-arm, open-label study to assess the efficacy and safety of baricitinib at RP2D in patients with thrombopoietin-receptor-agonist-refractory persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation. Patients in phase 1b who were treated with baricitinib at the RP2D will be included in the phase 2 efficacy endpoint analyses.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-70 years;
- •Underwent allo-HSCT;
- •Meet the diagnostic criteria for delayed platelet engraftment (DPE) or secondary failure of platelet recovery (SFPR);
- •Have platelet counts consistently <20 ×10^9/L or transfusion-dependent within 14 days prior to enrollment;
- •Have received adequate corticosteroid and TPO-RA therapy for persistent thrombocytopenia for no less than 4 weeks, with treatment failure or intolerance;
- •Complete donor chimerism.
排除标准
- •Relapse of hematologic malignancy or MRD positivity;
- •Active infection;
- •Active graft-versus-host disease;
- •Thrombotic microangiopathy;
- •Primary graft failure or poor graft function;
- •Presence of other factors that may lead to secondary thrombocytopenia at the time of PT diagnosis;
- •History of systemic herpes zoster infection within 12 weeks prior to enrollment screening;
- •Acute or chronic infection with HBV, HCV, or HIV;
- •Evidence of active tuberculosis, or history of active tuberculosis without documented standard anti-tuberculosis treatment, or close contact with active tuberculosis without documented standard tuberculosis prophylaxis;
- •Receipt of a live vaccine within 12 weeks prior to enrollment screening, or planned receipt of a live vaccine during the study period;
- •Clinically significant thromboembolic event within 24 weeks prior to enrollment screening, or current use of anticoagulant medications deemed by the investigator to carry an uncontrollable risk;
- •Estimated glomerular filtration rate <50 mL/min/1.73 m^2;
- •Severe pre-existing or current conditions involving the cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, nervous, or neuropsychiatric systems, or other severe or unstable illnesses or laboratory abnormalities that will make the study drug unacceptable for the patient or can interfere study data;
- •Participation in another clinical trial within 30 days prior to enrollment.
研究组 & 干预措施
Baricitinib
Group A: Open label baricitinib at 2 mg daily (Phase 1) Group B: Open label baricitinib at 4 mg daily (Phase 1) Group C: Open label baricitinib at the RP2D (Phase 2)
干预措施: Baricitinib (Drug)
结局指标
主要结局
Adverse events in the Ib part
时间窗: 24 weeks
The incidence and severity of adverse events are assessed using the criteria of CTCAE 5.0.
Overall response rate (ORR) for the IIa part
时间窗: 12 weeks
The proportion of patients achieving an overall response (OR), defined as a platelet count ≥20×10\^9/L maintained for more than 7 days without transfusion support. Platelet counts obtained within 4 weeks after rescue therapy were not included in the efficacy assessment.
次要结局
- Overall response rate (ORR) for the Ib part(12 weeks)
- Complete response (CR)(12 weeks)
- Durable response(24 weeks)
- Time to response(12 weeks)
- Bleeding events(24 weeks)
- Rescue medication(24 weeks)
- Adverse events in the IIa part(24 weeks)
- Overall Survival (OS)(104 weeks)
- Transplantation-related mortality (TRM)(104 weeks)
- Relapse or progression of underlying disease(104 weeks)
- Graft-versus-host disease(104 weeks)
研究者
Peng Zhao
Associate Research Fellow
Peking University People's Hospital