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

NCT07705308 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026255
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT)

Keywords

radiotherapy; MALT lymphoma; targeted therapy

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  The disappearance of all target lesions and the normalization of tumor marker levels, with no new lesions identified.

  6 months

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  6 months

• Duration of Response (DOR)

  6 months

• 2-year Event-Free Survival (EFS)

  2 years

• 2-year Overall Survival (OS)

  2 years

• 2-year Local Control Rate

  2 years

Study Arms (2)

research arm

EXPERIMENTAL

Patients will receive a total dose of 4 Gy, delivered as 2 consecutive daily fractions, encompassing all initially involved disease sites. Following radiotherapy, patients will then receive oral orelabrutinib at a dose of 150 mg once daily, administered in 4-week cycles for a total of 6 cycles.

Radiation: Radiation (Very low dose)

control arm

ACTIVE COMPARATOR

Patients will receive a total of 24 Gy in 12 fractions comprehensively to all initially involved sites of disease over 12 consecutive business days.

Radiation: Radiation (Standard)

Interventions

Radiation (Very low dose) RADIATION

4 Gy in 2 consecutive daily fractions subsequently with orelabrutinib

Also known as: targeted therapy

research arm

Radiation (Standard) RADIATION

24 Gy in 12 fractions

control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (3)

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200000, China

Location

Fudan University Affiliated Minhang Hospital

Shanghai, Shanghai Municipality, China

Location

Huadong Hospital

Shanghai, Shanghai Municipality, China

Location

Related Publications (2)

• 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: 10.1182/bloodadvances.2022009168.

  PMID: 37078706 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Radiation

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Shu-Bei Wang, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shu-Bei Wang, MD

CONTACT

+86-021-64370045; wangshubei@163.com

Gang Cai, MD

CONTACT

+86-021-64370045; cg11855@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 15, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): May 1, 2031
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)