This is a prospective, multicenter Phase 2 clinical trial named the MALT-RO study, evaluating ultra-low-dose radiation therapy followed by orelabrutinib as first-line treatment for adults with Stage I-II MALT lymphoma. The study aims to determine the efficacy and safety profile of this sequential regimen. Eligible participants aged 18 years or older with histologically confirmed MALT lymphoma, measurable lesions, no prior systemic anti-lymphoma therapy, adequate organ function, and an ECOG performance status of 0-1 will receive 4Gy ultra-low-dose radiation (2Gy daily for 2 consecutive days) followed by oral orelabrutinib 150mg once daily for up to 6 cycles (28 days per cycle). Patients with partial response or stable disease after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles or until disease progression. All participants will undergo regular safety monitoring, tumor assessments, and long-term follow-up every 3 months to evaluate treatment durability. This treatment strategy is designed to improve efficacy and achieve more favorable outcomes compared with standard approaches for MALT lymphoma, while minimizing treatment-related toxicities such as long-term organ damage, xerostomia, cataracts, and other complications related to conventional standard-dose radiation, thereby offering a well-tolerated, convenient, targeted therapeutic option for patients with MALT lymphoma under strict ethical oversight in accordance with the Declaration of Helsinki and Chinese Good Clinical Practice guidelines.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Orelabrutinib 150 mg tablets, administered orally once daily. Treatment consists of up to 6 consecutive 28-day cycles. Patients with partial response or stable disease without disease progression after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles.
The total radiation dose is 4 Gy, administered as 2 Gy per day for 2 consecutive days.
No. 1, East Banshan Road , Gongshu District
Hangzhou, Zhejiang, China
RECRUITINGThe First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGComplete Remission Rate (CRR)
Complete remission is defined as the disappearance of all target lesions and no new lesions appearing, assessed per the Lugano Response Criteria for Lymphoma.
Time frame: Assessed at the end of the treatment (approximately 6 cycles, up to 6 months from study start) .
Incidence of Adverse Events
Safety outcomes include the incidence, severity, and relationship to treatment of all adverse events (AEs) and serious adverse events (SAEs) monitored throughout the treatment and follow-up period.
Time frame: Throughout the treatment period and during the follow-up period (up to 12 months or until disease progression).
Objective Response Rate (ORR)
To evaluate the objective response rate (defined as the proportion of participants achieving complete remission \[CR\] or partial remission \[PR\]) in participants with Stage I-II MALT lymphoma treated with the sequential regimen, assessed per the Lugano Response Criteria.
Time frame: 3-month, 6-month, and 12-month follow-up visits.
Duration of Response (DOR)
To assess duration of response, defined as the time from the first documentation of objective response (CR or PR) to disease progression, recurrence, or death from any cause, per Lugano Response Criteria.
Time frame: Assessed every 3 months up to 24 months after study initiation.
Time to Response (TTR)
To evaluate time to response, defined as the time from study enrollment to the first documentation of objective response (CR or PR), assessed per the Lugano Response Criteria.
Time frame: Assessed at each on-treatment visit (every 4 weeks during 6 cycles of orelabrutinib) and follow-up visits.
Progression-Free Survival (PFS)
To assess progression-free survival, defined as the time from study enrollment to disease progression, recurrence, or death from any cause, per Lugano Response Criteria.
Time frame: Assessed every 3 months up to 24 months after study initiation.
Overall Survival (OS)
To evaluate time from study enrollment to death from any cause.
Time frame: 24 months
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