MALT LymphomaPhase 2NCT07554898
Ultra-low-dose Radiation Therapy Followed by Orelabrutinib as First-line Treatment for Stage Ⅰ-Ⅱ MALT Lymphoma
A Phase 2 study testing Orelabrutinib and Ultra-low-dose Radiation Therapy in people with MALT Lymphoma, run by Zhejiang Cancer Hospital at 2 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MALT Lymphoma
- What is being tested?
- Orelabrutinib and Ultra-low-dose Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesChina
- Study dates
- 16 Apr 2026to 1 Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years, all genders eligible;
- Histopathologically confirmed MALT lymphoma (extranodal marginal zone lymphoma) with at least one measurable lesion outside the spleen, with any diameter > 1.0 cm;
- No prior systemic anti-tumor therapy after diagnosis (including chemotherapy, targeted therapy, rituximab, etc.).
- Note: For patients with primary gastric MALT lymphoma, Helicobacter pylori (HP) must be negative or the patient must have failed standard HP eradication therapy. Patients with MZL who progressed or relapsed after local treatment (including surgery, Helicobacter pylori eradication, and hepatitis C treatment) are eligible for enrollment.
- ECOG performance status score of 0-1;
- Presence of treatment indications as judged by the investigator (including symptoms, cytopenias, risk of end-organ damage, bulky disease, or persistent progression);
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- Adequate major organ function, meeting the following criteria:
- Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelets ≥ 75 × 10⁹/L, hemoglobin ≥ 75 g/L; If bone marrow involvement is present: ANC ≥ 1.0 × 10⁹/L, platelets ≥ 50 × 10⁹/L, hemoglobin ≥ 50 g/L;
- Total bilirubin ≤ 1.5 × ULN, AST or ALT ≤ 2 × ULN, serum creatinine ≤ 1.5 × ULN, serum amylase ≤ ULN;
- International Normalized Ratio (INR) ≤ 1.5 × ULN.
- Expected survival ≥ 3 months;
- Voluntarily provide written informed consent before screening.
Who cannot join
- Current or history of other malignant tumors, except for those who have achieved complete remission after radical treatment;
- Lymphoma involvement of the central nervous system or transformation to high-grade lymphoma;
- Patients with other tumors who have not recovered from non-hematologic toxicities of prior anti-tumor therapy to ≤ Grade 1 (except for alopecia);
- Uncontrolled or significant cardiovascular diseases, including:
- Congestive heart failure of New York Heart Association (NYHA) Class II or above, unstable angina, myocardial infarction within 6 months before the first dose of the study drug, or arrhythmias requiring treatment at screening, or left ventricular ejection fraction (LVEF) < 50%;
- Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy);
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- History of clinically significant QTc interval prolongation, or QTc interval at screening > 470 ms for females or > 450 ms for males;
- Subjects with symptomatic coronary artery disease requiring medication;
- Uncontrolled hypertension (despite lifestyle modification and use of a reasonable and tolerable maximum dose of 3 or more antihypertensive drugs [including diuretics] for more than 1 month, blood pressure still not reaching target, or blood pressure can only be effectively controlled with 4 or more antihypertensive drugs);
- Active bleeding within 2 months before screening, or currently receiving anticoagulant drugs, or considered by the investigator to have a clear bleeding tendency;
- Urine protein ≥ 2+ and 24-hour urine protein quantification ≥ 2 g/24 hours;
- History of deep vein thrombosis or pulmonary embolism within the past 6 months;
- History of organ transplantation or allogeneic hematopoietic stem cell transplantation;
- Major surgery within 6 weeks before screening or minor surgery within 2 weeks before screening. Major surgery is defined as surgery performed under general anesthesia; however, diagnostic endoscopic procedures are not considered major surgery. Insertion of vascular access devices is exempt from this exclusion criterion;
- HIV/AIDS or other serious infectious diseases;
- Patients with severe pulmonary function impairment due to pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or other conditions;
- Previous treatment with BTK inhibitors, BCR pathway inhibitors (e.g., PI3K, Syk), or BCL-2 inhibitors;
- Subjects with drug abuse or alcohol abuse;
- Pregnant or lactating women, or subjects of childbearing potential who are unwilling to use contraceptive measures;
- Other conditions that, in the opinion of the investigator, make the subject unsuitable for participation in this trial.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
No. 1, East Banshan Road , Gongshu District
Hangzhou, Zhejiang, 310000
Yamin Tan, phD, 8657188122153, yamin0001@126.com
- Recruiting
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Yi Zhao, phD, 8657187233807, zhaoyi999@zju.edu.cn
About this study
Official title: Ultra-low-dose Radiation Therapy Followed by Orelabrutinib as First-line Treatment for Stage Ⅰ-Ⅱ MALT Lymphoma: A Prospective, Multicenter Phase Ⅱ Study
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.
- Conditions
- MALT Lymphoma
- Being tested
- Orelabrutinib, Ultra-low-dose Radiation Therapy
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrelabrutinibDrug
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.
Ultra-low-dose Radiation TherapyRadiation
The total radiation dose is 4 Gy, administered as 2 Gy per day for 2 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Ultra-low-dose Radiation Followed by Orelabrutinib | Experimental | All participants will receive a sequential treatment regimen: ultra-low-dose radiation therapy (total 4Gy, administered as 2Gy daily for 2 consecutive days), followed by oral orelabrutinib 150mg once daily for up to 6 cycles (28 days per cycle). Patients who achieve partial response or stable disease without disease progression after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles or until progression. Receives: Drug: Orelabrutinib; Radiation: Ultra-low-dose Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete 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.
Measured: 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.
Measured: Throughout the treatment period and during the follow-up period (up to 12 months or until disease progression).
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2026
- Study start16 Apr 2026 (estimated)
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MALT LymphomaStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, open-label, non-controlled Phase 2 study. All participants receive the same sequential treatment: ultra-low-dose radiation followed by orelabrutinib, with no control group or blinding.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Second Affiliated Hospital, Zhejiang University, School of Medicine, First Affiliated Hospital of Zhejiang University, Zhejiang Provincial People's Hospital, Zhejiang Provincial Tongde Hospital, Changxing County Traditional Chinese Medicine Hospital
- Responsible party
- Principal investigator, TanYamin, Zhejiang Cancer Hospital
- Investigators
- Yamin Tan, phD, Principal investigator, Zhejiang Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07554898
- Sponsor's protocol ID
- MALT-RO
- Status last verified
- May 2026
- First submitted
- 21 Apr 2026
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultra-low-dose Radiation Therapy Followed by Orelabrutinib as First-line Treatment for Stage Ⅰ-Ⅱ MALT Lymphoma: A Prospective, Multicenter Phase Ⅱ Study
- ClinicalTrials.gov ID
- NCT07554898
- Acronym / sponsor ID
- MALT-RO
- Conditions
- MALT Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Collaborators
- Second Affiliated Hospital, Zhejiang University, School of Medicine, First Affiliated Hospital of Zhejiang University, Zhejiang Provincial People's Hospital, Zhejiang Provincial Tongde Hospital, Changxing County Traditional Chinese Medicine Hospital
- Study start
- 16 Apr 2026 (estimated)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 28 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, open-label, non-controlled Phase 2 study. All participants receive the same sequential treatment: ultra-low-dose radiation followed by orelabrutinib, with no control group or blinding.
| Arm | Type | Receives |
|---|---|---|
| Ultra-low-dose Radiation Followed by Orelabrutinib | Experimental | Drug: Orelabrutinib, Radiation: Ultra-low-dose Radiation TherapyAll participants will receive a sequential treatment regimen: ultra-low-dose radiation therapy (total 4Gy, administered as 2Gy daily for 2 consecutive days), followed by oral orelabrutinib 150mg once daily for up to 6 cycles (28 days per cycle). Patients who achieve partial response or stable disease without disease progression after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles or until progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 18 years, all genders eligible;
- Histopathologically confirmed MALT lymphoma (extranodal marginal zone lymphoma) with at least one measurable lesion outside the spleen, with any diameter > 1.0 cm;
- No prior systemic anti-tumor therapy after diagnosis (including chemotherapy, targeted therapy, rituximab, etc.).
- Note: For patients with primary gastric MALT lymphoma, Helicobacter pylori (HP) must be negative or the patient must have failed standard HP eradication therapy. Patients with MZL who progressed or relapsed after local treatment (including surgery, Helicobacter pylori eradication, and hepatitis C treatment) are eligible for enrollment.
- ECOG performance status score of 0-1;
Key exclusion criteria (20 listed)
- Current or history of other malignant tumors, except for those who have achieved complete remission after radical treatment;
- Lymphoma involvement of the central nervous system or transformation to high-grade lymphoma;
- Patients with other tumors who have not recovered from non-hematologic toxicities of prior anti-tumor therapy to ≤ Grade 1 (except for alopecia);
- Uncontrolled or significant cardiovascular diseases, including:
- Active bleeding within 2 months before screening, or currently receiving anticoagulant drugs, or considered by the investigator to have a clear bleeding tendency;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OrelabrutinibOrelabrutinib 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. | Drug | Ultra-low-dose Radiation Followed by Orelabrutinib |
| Ultra-low-dose Radiation TherapyThe total radiation dose is 4 Gy, administered as 2 Gy per day for 2 consecutive days. | Radiation | Ultra-low-dose Radiation Followed by Orelabrutinib |
Primary outcome
Complete Remission Rate (CRR)
Time frame: Assessed at the end of the treatment (approximately 6 cycles, up to 6 months from study start) .
Complete remission is defined as the disappearance of all target lesions and no new lesions appearing, assessed per the Lugano Response Criteria for Lymphoma.
Incidence of Adverse Events
Time frame: Throughout the treatment period and during the follow-up period (up to 12 months or until disease progression).
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.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: 3-month, 6-month, and 12-month follow-up visits.
Duration of Response (DOR)
Time frame: Assessed every 3 months up to 24 months after study initiation.
Time to Response (TTR)
Time frame: Assessed at each on-treatment visit (every 4 weeks during 6 cycles of orelabrutinib) and follow-up visits.
Progression-Free Survival (PFS)
Time frame: Assessed every 3 months up to 24 months after study initiation.
Overall Survival (OS)
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yamin Tan, phD principal investigator
Zhejiang Cancer Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Orelabrutinib and Ultra-low-dose Radiation Therapy in people with MALT Lymphoma, run by Zhejiang Cancer Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiaolin Yuan, MD (8657188122153, yuanxiaolinhaha@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission Rate (CRR) (time frame: Assessed at the end of the treatment (approximately 6 cycles, up to 6 months from study start) .). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.