Response-adapted Luvometinib With or Without Cytarabine in Langerhans Cell Histiocytosis

Официальное название

Luvometinib Monotherapy or Combined With Cytarabine for Langerhans Cell Histiocytosis: A Response-adapted, Interventional, Prospective Study

Обзор

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.

Вмешательства

• Препарат Luvometinib
  Luvometinib is administered orally once daily in 35-day cycles. Adult participants receive 8 mg once daily. Pediatric participants receive body-surface-area-adjusted dosing at 5 mg/m² once daily, rounded according to protocol with a maximum single dose of 8 mg. Luvometinib is used during induction and maintenance according to the assigned response path.
• Препарат Luvometinib, Cytarabine.
  Luvometinib is administered as described for induction and maintenance. In the B response path, cytarabine is administered at 100 mg/m² by subcutaneous injection on days 1-5 of each 35-day cycle for 12 cycles, followed by luvometinib maintenance for 6 additional 35-day cycles.

Первичные конечные точки

• Objective response rate after six cycles of luvometinib induction by blinded independent central review [Срок оценки: At completion of six 35-day cycles, approximately week 30 / target C7D1 +/- 7 days]
• Incidence of adverse events and serious adverse events [Срок оценки: 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]

Вторичные конечные точки (6)

• Kaplan-Meier estimated progression-free survival rate at 24 months [Срок оценки: 24 months after first dose]
• Time to response among CMR/PMR responders [Срок оценки: 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 [Срок оценки: 12 and 24 months after first dose]
• Objective response rate at cycles 12, 18, and 24 [Срок оценки: At the end of Cycle 12, 18, and 24 (each cycle is 35 days)]
• Disease control rate at cycles 12, 18, and 24 [Срок оценки: At the end of Cycle12, 18, and 24 (each cycle is 35 days)]
• Clinical benefit rate at cycles 12, 18, and 24 [Срок оценки: At the end of Cycle 12, 18, and 24 (each cycle is 35 days)]

Критерии участия

Критерии включения

• 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 >=60.
• Adequate organ function as defined in the protocol.
• Written informed consent from adult participants or legal guardians, with participant assent when applicable.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07728201 · LUCAS-2026-V4.0

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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