NCT07476872尚未招募1 期
A Single-Arm, Open-Label, Single-Center Phase Ib/IIa Clinical Study of Gecacitinib in the Treatment of Steroid-Refractory/Dependent Active Chronic Graf Versus Host Disease (cGVHD).
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 33
- 主要终点
- phase Ib: Maximal Tolerable Dose (MTD)
研究概览
简要总结
This study aims to evaluate the safety and efficacy of Gecacitinib in patients with steroid-refractory/dependent active chronic graft versus host disease (cGVHD).
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
- •Age ≥ 18 years, regardless of gender.
- •Underlying hematologic malignancies or non-malignant disorders having received allogeneic hematopoietic stem cell transplantation.
- •Diagnosis of active cGVHD according to the 2014 NIH consensus criteria, meeting the definition of steroid-refractory or steroid-dependent cGVHD. Prior lines of cGVHD therapy are not restricted. Definitions are as follows:
- •Steroid-refractory cGVHD is defined as meeting any of the following criteria: disease progression despite the use of prednisone ≥1 mg/kg/day (or equivalent dose of corticosteroids) for at least 1 week; OR, persistent disease symptoms with no improvement despite the use of prednisone ≥0.5 mg/kg/day or ≥1 mg/kg every other day (or equivalent dose of corticosteroids) for at least 4 weeks.
- •Steroid-dependent cGVHD is defined as the requirement for a maintenance dose of prednisone >0.25 mg/kg/day or >0.5 mg/kg every other day (or equivalent dose of corticosteroids) to prevent disease flare or progression, and failure to successfully taper the dose to a lower level in at least 2 separate attempts spaced ≥8 weeks apart.
- •Platelet count ≥50 × 10⁹/L and absolute neutrophil count (ANC) ≥0.5 × 10⁹/L, without the use of colony-stimulating factors, androgens, erythropoietin, thrombopoietin, or platelet transfusion within 7 days prior to screening.
- •Adequate major organ function, defined as meeting the following criteria: ALT and AST ≤ 2.5 × upper limit of normal (ULN); direct and total bilirubin ≤ 2.0 × ULN; serum creatinine ≤ 1.5 × ULN.
- •Stable underlying disease without evidence of progression or relapse.
- •Karnofsky Performance Status (KPS) ≥ 60%.
- •Voluntarily participate in this study, provide signed informed consent, demonstrate good compliance, and be able to adhere to the study and follow-up procedures
排除标准
- •Post-transplant lymphoproliferative disorder, or loss of full donor chimerism due to other reasons.
- •Previous use of, or current treatment with, other JAK inhibitors at the time of screening.
- •History or presence of major diseases or clinically significant organ dysfunction that cannot be adequately controlled by treatment and may interfere with study completion:
- •Congestive heart failure of New York Heart Association (NYHA) class III-IV, or documented history of diastolic or systolic dysfunction (e.g., left ventricular ejection fraction <40% by echocardiography), or uncontrolled/unstable angina or myocardial infarction.
- •Uncontrolled diabetes (blood glucose >250 mg/dL or >13.9 mmol/L).
- •Hypertension that cannot be adequately controlled to systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg despite combination antihypertensive therapy.
- •Peripheral neuropathy (Grade 2 or higher per NCI-CTCAE v5.0 criteria).
- •Patients with any uncontrolled bacterial, viral, or fungal infection.
- •Positive for HIV at screening, or active hepatitis B virus infection (HBsAg positive and HBV-DNA positive or above the upper limit of normal), or positive for HCV antibody with detectable HCV-RNA.
- •History of tuberculosis or positive interferon-γ release assay at screening.
- •Concurrent use of strong CYP3A4 inhibitors.
- •History of progressive multifocal leukoencephalopathy.
- •Known or suspected hypersensitivity to Gecacitinib hydrochloride, drugs of the same class, or any of their excipients.
- •Pregnant or lactating women, or patients unwilling to use effective contraception during Gecacitinib treatment and for 1 week after the last dose.
- •Inability to swallow oral tablets.
研究组 & 干预措施
Gecacitinib treatment
Experimental
干预措施: Gecacitinib (Drug)
结局指标
主要结局
phase Ib: Maximal Tolerable Dose (MTD)
时间窗: Baseline up to 28 days
If dose limiting toxicity (DLT) occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD. (Patients in phase Ib)
phase IIa: Overall response rate (ORR) on Cycle 7 Day 1
时间窗: Cycle 7 Day 1
Percentage of participants achieving complete response (CR) and partial response (PR) during the study according to the cGVHD 2014 NIH Consensus Criteria.
次要结局
- phase Ib: Recommended phase II dose (RP2D)(Baseline up to 28 days)
- phase IIa: Rate of Failure-free Survival (FFS)(Baseline to when the last participant reached Cycle 7 Day 1)
- phase IIa: Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score(Cycle 7 Day 1)
- phase IIa: Best overall response (BOR)(Cycle 7 Day 1)
- phase IIa: Proportion of patients who achieved ORR (CR+PR) at Cycle 4 Day 1.(Cycle 4 Day 1)
- phase IIa: Duration of Response (DOR)(From first response until cGVHD progression, death, or the date of change/addition of systemic therapies for cGVHD, whichever comes first, assessed up to Cycle 7 Day 1.)
- phase IIa: Organ-Specific Response Rate(Cycle 7 day 1)
- phase IIa: Proportion of patients with ≥50% reduction in daily steroid dose(Cycle 7 Day1)
- phase IIa: Proportion of patients successfully tapered off all steroids(Cycle 7 Day 1)
- phase IIa: Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)(Baseline; up to Cycle 7 Day 1)
- phase IIa: Change From Baseline in EQ-5D-5L(Baseline; up to Cycle 7 Day 1)
- phase IIa: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)(From first dose to 28 days post last dose, up to Cycle 8 Day 1)
研究者
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