The Safety and Efficacy of Gecacitinib (Also Known as Jaktinib) Combined Glucocorticoids as First-line Treatment for Grade II-IV Acute Graft-versus-host Disease.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Reactions by Dosage Group in Patients with Grade II-IV Acute GVHD Treated with First-Line Gecacitinib (also known as Jaktinib) and corticosteroids
研究概览
简要总结
This study aims to evaluate the optimal dose (Recommended Phase 2 Dose, RP2D), preliminary safety, and efficacy of gecacitinib (also known as jaktinib) in combination with glucocorticoids as first-line therapy for patients with grade II-IV acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
详细描述
This study is a single-center, single-arm, prospective interventional trial utilizing a 3+3 dose escalation design to evaluate the safety and efficacy of first-line gecacitinib (also known as jaktinib) in combination with glucocorticoids for the treatment of grades II-IV acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
A total of 35 patients will be enrolled across both the dose exploration phase (using the 3+3 design to determine the Recommended Phase 2 Dose [RP2D]) and the efficacy evaluation phase (where additional patients are treated at the RP2D to further assess efficacy and safety).
The primary objectives include:
- Determining the RP2D of gecacitinib (also known as jaktinib) in combination with glucocorticoids.
- Assessing the safety profile (e.g., incidence and severity of adverse events).
- Evaluating efficacy (e.g., overall response rate at Day 28). Secondary endpoints may include duration of response, survival outcomes, and biomarker analyses.
This design is appropriate for early-phase trials seeking to establish dosing and preliminary activity of a novel combination therapy in a high-risk population.
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 provide signed informed consent and be ≥18 years of age at the time of consent.
- •Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood.
- •Have received systemic glucocorticoid therapy for no more than 2 days prior to enrollment.
- •Demonstrate clear myeloid and platelet engraftment: absolute neutrophil count (ANC) > 1.0 × 10⁹/L and platelet count > 50 × 10⁹/L (permitted use of growth factors or transfusion support).
- •Clinical diagnosis of grade II-IV acute GVHD (aGVHD) per the MAGIC (Mount Sinai Acute GVHD International Consortium) criteria (Appendix 1).
- •ECOG performance status of 0-
- •Life expectancy > 4 weeks.
- •Able to swallow tablets.
- •Willing and able to comply with study procedures and follow-up.
排除标准
- •History of ≥2 allo-HSCT procedures.
- •Development of aGVHD following unplanned donor lymphocyte infusion (DLI) for relapse of underlying malignancy. Note: Planned DLI as part of the transplant protocol is permitted.
- •Concurrent treatment with another JAK inhibitor. Note: Patients who previously discontinued JAK inhibitors due to toxicity (not refractory aGVHD) are eligible.
- •Active bleeding.
- •Diagnosed or suspected chronic GVHD.
- •Uncontrolled active infection, defined as sepsis-induced hemodynamic instability or progressive symptoms/signs/imaging findings attributable to infection. Asymptomatic or persistent fever alone is not exclusionary.
- •unresolved toxicity or complications from allo-HSCT (excluding aGVHD).
- •Clinically significant abnormalities that may compromise safety, including: a) Uncontrolled diabetes (fasting glucose >13.9 mmol/L); b) Hypertension unresponsive to ≥2 agents (systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg); c) Peripheral neuropathy ≥Grade 2 (per NCI CTCAE v5.0).
- •Within 6 months prior to screening: NYHA Class III/IV heart failure, unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism.
- •Arrhythmia requiring treatment or QTcB interval >480 ms at screening.
- •Severe renal impairment (serum creatinine >1.5 × ULN) at screening.
- •Pre-transplant history of gastrointestinal ulcers, gastrectomy, or intestinal resection that may impair drug absorption.
- •Major surgery within 4 weeks prior to screening without full recovery.
- •Cholestatic disorders or hepatic sinusoidal obstruction syndrome (SOS/VOD) at screening (defined as persistent hyperbilirubinemia and organ dysfunction unrelated to GVHD).
- •Active uncontrolled viral infections at screening: HBV: HBsAg⁺ with detectable HBV-DNA, or detectable HBV-DNA regardless of HBsAg status; HCV: Anti-HCV antibody⁺ with detectable HCV-RNA.
- •History of active tuberculosis within 6 months prior to screening.
- •Epilepsy or current use of psychotropic/sedative medications.
- •Pregnancy, lactation, or intention to conceive; male patients unwilling to use condoms during treatment and for 2 days after the last dose.
- •Other active malignancies (excluding the transplanted hematologic malignancy) within 5 years.
- •Current use of anticoagulants or antiplatelet agents (except low molecular weight heparin).
- •Any condition that, in the investigator's judgment, may compromise patient safety or protocol compliance.
- •Known hypersensitivity to jaktinib, its analogs, or excipients.
- •Participation in another interventional clinical trial within 4 weeks prior to screening.
- •Investigator determination of unsuitability for the study.
研究组 & 干预措施
Gecacitinib (also known as Jaktinib) group
Patients accept Gecacitinib (also known as Jaktinib) combined glucocorticoids treatment
干预措施: Gecacitinib (also known as Jaktinib) combined glucocorticoids (Drug)
结局指标
主要结局
Incidence of Adverse Reactions by Dosage Group in Patients with Grade II-IV Acute GVHD Treated with First-Line Gecacitinib (also known as Jaktinib) and corticosteroids
时间窗: 28 days
The primary outcome of this study was the incidence of adverse reactions, stratified by Gecacitinib (also known as Jaktinib) dosage group, in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) receiving first-line treatment with Gecacitinib (also known as Jaktinib) in combination with corticosteroids.
The Day 28 Overall Response Rate (ORR) in patients with grade II-IV acute graft-versus-host disease (GVHD) treated with Ggecacitinib (also known as Jaktinib) in combination with corticosteroids as first-line therapy.
时间窗: 28 days
The Day 28 Overall Response Rate (ORR) in patients with grade II-IV acute graft-versus-host disease (GVHD) treated with Gecacitinib (also known as Jaktinib) in combination with corticosteroids as first-line therapy.
次要结局
- To determine the Recommended Phase 2 Dose (RP2D) of Jaktinib for the efficacy evaluation phase.(28 days)
- Overall Response Rate (ORR) at Weeks 1, 2, 6, 8, 12, and 24 following treatment with Jaktinib in combination with corticosteroids.(Weeks 1, 2, 6, 8, 12, and 24)
- Duration of Response (DOR)(1 year)
- 180-day cumulative non-relapse mortality (NRM)(180 days)
- Change in levels of serum biomarkers(Days 7, 14, and 28)
- 1-year GVHD-free, relapse-free survival (GRFS)(1 year)
- 1-year cumulative incidence of moderate-to-severe chronic graft-versus-host disease (cGVHD).(1 year)
- Immune reconstitution at Weeks 4, 12, and 24 post-transplantation(Weeks 4, 12, and 24 post-transplantation)
研究者
Yi Luo
Professor
First Affiliated Hospital of Zhejiang University