A Prospective Study of Response-adapted Low-dose Radiotherapy Combined With Orelabrutinib for Localized Mucosa-associated Lymphoid Tissue Extranodal Marginal Zone Lymphoma

Обзор

Multi center, randomized, controlled, prospective clinical trial to explore the clinical efficacy and safety of low-dose radiotherapy combined with targeted therapy for localized MALT lymphoma.

Вмешательства

• Лучевая терапия Radiation (Very low dose)
  4 Gy in 2 consecutive daily fractions subsequently with orelabrutinib
• Лучевая терапия Radiation (Standard)
  24 Gy in 12 fractions

Первичные конечные точки

• Complete response rate [Срок оценки: 6 months]

Вторичные конечные точки (8)

• Objective Response Rate (ORR) [Срок оценки: 6 months]
• Duration of Response (DOR) [Срок оценки: 6 months]
• 2-year Event-Free Survival (EFS) [Срок оценки: 2 years]
• 2-year Overall Survival (OS) [Срок оценки: 2 years]
• 2-year Local Control Rate [Срок оценки: 2 years]
• 2-year Distant Metastasis Rate [Срок оценки: 2 years]
• Rate of acute toxicity (any and above grade 3) [Срок оценки: From enrollment to 3 months after treatment]
• Rate of late toxicity (any and above grade 3) [Срок оценки: After 3 months of enrollment]

Критерии участия

Критерии включения

• Patients must meet all of the following criteria to be eligible for enrollment in this study:
• The patient voluntarily agrees to participate in this study and provides written informed consent;
• Age ≥ 18 years;
• Histopathologically confirmed diagnosis of extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type;
• Involved sites include but are not limited to: orbit, parotid gland, thyroid, Helicobacter pylori (H. pylori)-negative gastric MALT (in this study, H. pylori-negative gastric MALT is defined as negative results on both gastric mucosal tissue biopsy and serum H. pylori antibody test within the past 6 months; for patients with unknown prior H. pylori status who have received anti-H. pylori therapy, a positive serum H. pylori antibody test is permissible, provided that a subsequent gastroscopy or urea breath test confirms negativity);
• Lugano stage I-II disease;
• Able to swallow tablets normally;
• Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0-2;
• No prior radiotherapy, chemotherapy, targeted therapy, or immunotherapy for MALT lymphoma;
• Life expectancy ≥ 12 months;
• Adequate major organ function, meeting the following criteria:

• Hematological parameters: absolute neutrophil count ≥ 1.0 × 10⁹/L; platelet count ≥ 50 × 10⁹/L; hemoglobin ≥ 80 g/L;
• Biochemical parameters: total bilirubin < 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN; serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 50 mL/min;
• Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment and must agree to use highly effective methods of contraception during the study period and for 120 days after the last dose. Male patients with female partners of childbearing potential must be surgically sterile or agree to use highly effective methods of contraception during the study period and for 120 days after the last dose.

Критерии исключения

• Patients who meet any of the following criteria will be excluded from enrollment in this study:
• Major surgery (excluding diagnostic surgery) within 4 weeks prior to enrollment;
• Previous or concurrent diagnosis of another malignancy, with the exception of adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the breast;
• Active chronic hepatitis B infection, defined as detectable HBV DNA;
• Active HIV or syphilis infection;
• Presence of severe concomitant medical conditions or circumstances that may affect the patient's eligibility or safety during the study period;
• Pregnant or breastfeeding women;
• Presence of active psychiatric disorders or other psychological conditions that may impair the patient's ability to provide informed consent or understand the study procedures;
• Patients considered by the investigator to have poor compliance; Pathologically or radiologically confirmed distant metastasis; Other factors that, in the investigator's judgment, may affect the study results or necessitate premature termination of the study, including but not limited to alcohol abuse, drug abuse, other severe diseases (including psychiatric disorders) requiring concomitant treatment, significant laboratory abnormalities, or family/social circumstances that may compromise patient safety.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Шанхай
• Fudan University Affiliated Minhang Hospital — Шанхай
• Huadong Hospital — Шанхай

Публикации

• Deng LJ, Zhou KS, Liu LH, Zhang MZ, Li ZM, Ji CY, Xu W, Liu T, Xu B, Wang X, Gao SJ, Zhang HL, Hu Y, Li Y, Cheng Y, Yang HY, Cao JN, Zhu ZM, Hu JD, Zhang W, Jing HM, Ding KY, Zhang XY, Zhao RB, Zhang B, Tian YM, Song YP, Song YQ, Zhu J. Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 Aug 22;7(16):4349-4357. doi: PMID 37078706
• Pinnix CC, Dabaja BS, Gunther JR, Fang PQ, Wu SY, Nastoupil LJ, Strati P, Nair R, Ahmed S, Steiner R, Westin J, Neelapu S, Rodriguez MA, Lee HJ, Wang M, Flowers C, Feng L, Esmaeli B. Response-Adapted Ultralow-Dose Radiation Therapy for Orbital Indolent B-Cell Lymphoma: A Phase 2 Nonrandomized Controlled Trial. JAMA Oncol. 2024 Sep 1;10(9):1195-1203. doi: 10.1001/jamaoncol.2024.2112. PMID 38990564

Идентификаторы

NCT: NCT07705308 · 2026255

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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