Luvometinib Monotherapy or Combined With Cytarabine for Langerhans Cell Histiocytosis: A Response-adapted, Interventional, Prospective Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Objective response rate after six cycles of luvometinib induction by blinded independent central review
研究概览
简要总结
This single-center, prospective, interventional phase 2 study evaluates a response-adapted treatment strategy for patients aged 10 years and older with histologically confirmed Langerhans cell histiocytosis requiring systemic therapy. All participants receive six 35-day cycles of luvometinib induction. Post-induction treatment follows the cycle 6 PET/CT response: participants with complete metabolic response continue luvometinib maintenance without cytarabine, whereas participants without complete metabolic response who are judged suitable to continue protocol treatment receive luvometinib plus cytarabine followed by luvometinib maintenance; participants with progression or otherwise unsuitable to continue protocol treatment may receive other standard therapy or discontinue study treatment per protocol. The primary endpoint is objective response rate after six cycles by blinded independent central review.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Open-label treatment. Protocol-defined PET/CT response endpoints are assessed by blinded independent central review (BICR). Post-discontinuation clinically performed imaging or documentation used only for PFS event recording may be investigator-adjudicated, with BICR review or audit when feasible. BICR reviewers are not involved in treatment decisions, safety management, or emergency medical handling.
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed Langerhans cell histiocytosis (LCH).
- •Age 10 years or older.
- •Systemic treatment indication and at least one PET response criteria-evaluable lesion.
- •Expected survival of at least 12 weeks, as judged by the investigator, and able to undergo protocol-specified treatment, assessments, and follow-up.
- •ECOG performance status 0-2 or Lansky score >=
- •Adequate organ function as defined in the protocol.
- •Written informed consent from adult participants or legal guardians, with participant assent when applicable.
排除标准
- •Hypersensitivity to luvometinib or any excipient.
- •Concurrent other malignant tumor.
- •Pregnancy or breastfeeding.
- •Failure to meet protocol contraception requirements.
- •Active bacterial, fungal, or viral infection.
- •Significant retinal disease or glaucoma.
- •NYHA class >=3 heart failure or LVEF <50%.
- •Psychiatric disease or other condition preventing protocol compliance.
- •Investigator judgment that participation is unsuitable.
结局指标
主要结局
Objective response rate after six cycles of luvometinib induction by blinded independent central review
时间窗: At completion of six 35-day cycles, approximately week 30 / target C7D1 +/- 7 days
Proportion of full analysis set participants achieving complete metabolic response (CMR) or partial metabolic response (PMR) by PET response criteria at the cycle 6 assessment window (target C7D1 +/- 7 days), as determined by blinded independent central review. No subsequent confirmatory PET/CT is required. The analysis is descriptive and will report the point estimate with an exact two-sided 95% confidence interval; no confirmatory hypothesis test is planned. Mild out-of-window assessments may be included with protocol deviation documentation if no major treatment or disease-status change affects interpretation. Clearly out-of-window, non-evaluable, or unreliable assessments, death, progression, treatment discontinuation due to toxicity, withdrawal from study treatment, or non-evaluable imaging before the cycle 6 assessment are counted as non-responders.
Incidence of adverse events and serious adverse events
时间窗: Routine AE recording: consent to 30 days after last study treatment; TEAE summaries from first dose; SAEs, study-related AEs, pregnancy, and important safety information followed per protocol
AEs, TRAEs, grade \>=3 AEs, SAEs, deaths, and clinically significant laboratory abnormalities summarized by NCI-CTCAE v5.0 and MedDRA SOC/PT. All AEs after informed consent will be recorded; treatment-emergent summaries will start at first study treatment and be summarized by actual exposure period, including luvometinib monotherapy, luvometinib plus cytarabine, and post-progression or salvage treatment descriptions as applicable. SAEs, study-related AEs, pregnancy, and important safety information after study treatment discontinuation may be followed during continued follow-up unless follow-up consent is withdrawn.
次要结局
- Kaplan-Meier estimated progression-free survival rate at 24 months(24 months after first dose)
- Time to response among CMR/PMR responders(From first dose through the first documented CMR/PMR, up to 24 cycles (each cycle is 35 days))
- Kaplan-Meier estimated overall survival rate at 12 and 24 months(12 and 24 months after first dose)
- Objective response rate at cycles 12, 18, and 24(At the end of Cycle 12, 18, and 24 (each cycle is 35 days))
- Disease control rate at cycles 12, 18, and 24(At the end of Cycle12, 18, and 24 (each cycle is 35 days))
- Clinical benefit rate at cycles 12, 18, and 24(At the end of Cycle 12, 18, and 24 (each cycle is 35 days))
研究者
Qi Zhu
Principal Investigator
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University