Central Nervous System LymphomaPhase 2ZillionNCT07405255
Zillion: Zanubrutinib Combined With Chemotherapy for Newly Diagnosed CNS Lymphoma
A Phase 2 study testing Zanubrutinib + Rituximab + MTX ± Selinexor in people with Central Nervous System Lymphoma, run by Ruijin Hospital at 1 site in China.
Trial summary
Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Central Nervous System Lymphoma
- What is being tested?
- Zanubrutinib + Rituximab + MTX ± Selinexor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteChina
- Study dates
- 30 Jan 2026to 30 Dec 2028
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a full understanding of this study and voluntarily sign the informed consent form.
- Untreated patients with primary central nervous system lymphoma (PCNSL) confirmed by pathology (immunotyping) according to the 2016 WHO classification of lymphoid neoplasms.
- Diffuse large B-cell lymphoma (DLBCL) originating from the central nervous system (CNS) without involvement of other organs, confirmed by PET-CT or contrast-enhanced CT.
- Expected survival greater than 3 months.
- Laboratory test results meeting all of the following:
- Creatinine clearance rate ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).
Show all 11Show fewer
- International normalized ratio (INR) ≤ 1.5 × ULN or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Patients on warfarin may have INR 2-3.
- Left ventricular ejection fraction (LVEF) ≥ 50%.
- Glomerular filtration rate (GFR) ≥ 60 mL/min.
- Male or female patients of childbearing potential must agree to use effective contraception (e.g., double-barrier methods, condoms, oral or injectable contraceptives, intrauterine device) during the study and for 30 days after the last dose.
- Postmenopausal women (> 45 years old and amenorrheic > 1 year) or surgically sterilized women are exempt from this requirement.
Who cannot join
- Contraindication to any drug included in the treatment regimen.
- History of clinically significant liver disease, including viral or other hepatitis or cirrhosis.
- Hepatitis B: Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV-DNA above ULN.
- Active hepatitis C: Positive HCV antibody with detectable HCV-RNA.
- Human Immunodeficiency Virus (HIV) infection.
- Congestive heart failure (New York Heart Association Class > II) or history within 6 months of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack.
Show all 12Show fewer
- Hereditary long QT syndrome or QTc > 480 ms (QTc calculated using Fridericia's formula, QTcF = QT / RR^0.33).
- Other malignancies within 5 years, except: completely cured cervical carcinoma in situ, basal cell carcinoma of the skin, breast carcinoma in situ, or another primary cancer that has been cured and not recurred within 5 years.
- Pregnant or lactating women, or women planning pregnancy during the study period.
- History of significant neurological or psychiatric disorders, including substance or psychotropic-drug abuse.
- Clinically significant active infection.
- Inability to take or swallow oral medication, or conditions affecting drug absorption (e.g., chronic diarrhea, intestinal obstruction).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Clinical Study on the Efficacy and Safety of Zanubrutinib Combined With Chemotherapy for Continuous Maintenance Treatment of Newly Diagnosed Central Nervous System Lymphoma
Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. After the results of the second-generation sequencing were reported, selinisol was added to the original treatment plan for those with TP53 mutations, and the original treatment plan was continued for those without TP53 mutations. Each course of treatment lasts for three weeks. A mid-term assessment is conducted after three courses of treatment, and a final assessment is carried out after six courses of treatment. After the mid-term or final assessment:
If the PR is not achieved or the disease progresses at any time, the subjects are withdrawn from the group and receive salvage treatment.
Read more
If the subjects achieve CR or PR, they enter maintenance treatment and continue with zanubrutinib for 2 years. For young patients (< 65 years old), they can choose whether to receive ASCT as consolidation treatment according to their personal will, and then follow up and observe until 3 years have passed.
SD/PD patients receive subsequent treatment after being judged by the researchers
- Conditions
- Central Nervous System Lymphoma
- Being tested
- Zanubrutinib + Rituximab + MTX ± Selinexor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zanubrutinib + Rituximab + MTX ± SelinexorDrug
This is a single-arm interventional study. Participants will undergo an induction phase consisting of six 21-day cycles. During induction, all participants receive:
Zanubrutinib 160 mg orally twice daily, Rituximab 375 mg/m² intravenous on Day 0, MTX 3.5 mg/m² intravenous on Days 1.
Before the second treatment cycle, participants will be tested for TP53 mutation status. Participants who test positive for the TP53 mutation will receive Selinexor 40 mg orally on Days 1 weekly added to their treatment regimen.
Following induction, participants enter a maintenance phase with:
Zanubrutinib 160 mg orally twice daily, continued for up to 2 years or until disease progression or unacceptable toxicity.
This design allows biomarker-driven treatment modification within a single treatment arm without randomization or separate comparator groups.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm: Zanubrutinib + Rituximab + MTX ± Selinexor | Experimental | This single treatment arm includes an induction phase of six 21-day cycles where participants receive:
Zanubrutinib 160 mg orally twice daily, Rituximab 375 mg/m² intravenously on Day 0, MTX 3.5 mg/m² intravenously on Days 1.
Before starting the second cycle, TP53 mutation status will be assessed. Participants positive for TP53 mutation will have Selinexor 60 mg orally added on Days 1 and 3 weekly.
Following induction, a maintenance phase consists of Zanubrutinib 160 mg orally twice daily for up to 2 years or until disease progression or unacceptable toxicity.
This study uses a biomarker-driven approach within a single-arm design without randomization or comparator arms. Receives: Drug: Zanubrutinib + Rituximab + MTX ± Selinexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission Rate (CRR)
Complete Remission Rate (CRR) is defined as the proportion of participants achieving complete remission based on predefined hematologic and/or imaging criteria at the end of treatment Cycle 6.
Measured: At the end of Cycle 6 and at 4 weeks after completion of Cycle 6 (each cycle is 21 days).
Secondary outcomes (1)
Overall Survival (OS)
Overall Survival (OS) is defined as the time from initiation of study treatment to death from any cause. Participants who are alive at the time of analysis will be censored at the date they were last known to be alive. OS will be summarized using the Kaplan-Meier method.
Measured: From initiation of study treatment to death from any cause or last follow-up, whichever occurs first, up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2026
- Study start30 Jan 2026 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Ruijin 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
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhao Weili, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07405255
- Sponsor's protocol ID
- Zillion
- Acronym
- Zillion
- Status last verified
- Feb 2026
- First submitted
- 8 Aug 2025
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on the Efficacy and Safety of Zanubrutinib Combined With Chemotherapy for Continuous Maintenance Treatment of Newly Diagnosed Central Nervous System Lymphoma
- ClinicalTrials.gov ID
- NCT07405255
- Acronym / sponsor ID
- Zillion / Zillion
- Conditions
- Central Nervous System Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 30 Jan 2026 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 12 Feb 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.
Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. After the results of the second-generation sequencing were reported, selinisol was added to the original treatment plan for those with TP53 mutations, and the original treatment plan was continued for those without TP53 mutations. Each course of treatment lasts for three weeks. A mid-term assessment is conducted after three courses of treatment, and a final assessment is carried out after six courses of treatment. After the mid-term or final assessment:
If the PR is not achieved or the disease progresses at any time, the subjects are withdrawn from the group and receive salvage treatment.
If the subjects achieve CR or PR, they enter maintenance treatment and continue with zanubrutinib for 2 years. For young patients (< 65 years old), they can choose whether to receive ASCT as consolidation treatment according to their personal will, and then follow up and observe until 3 years have passed.
SD/PD patients receive subsequent treatment after being judged by the researchers
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm: Zanubrutinib + Rituximab + MTX ± Selinexor | Experimental | Drug: Zanubrutinib + Rituximab + MTX ± SelinexorThis single treatment arm includes an induction phase of six 21-day cycles where participants receive: Zanubrutinib 160 mg orally twice daily, Rituximab 375 mg/m² intravenously on Day 0, MTX 3.5 mg/m² intravenously on Days 1. Before starting the second cycle, TP53 mutation status will be assessed. Participants positive for TP53 mutation will have Selinexor 60 mg orally added on Days 1 and 3 weekly. Following induction, a maintenance phase consists of Zanubrutinib 160 mg orally twice daily for up to 2 years or until disease progression or unacceptable toxicity. This study uses a biomarker-driven approach within a single-arm design without randomization or comparator arms. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Have a full understanding of this study and voluntarily sign the informed consent form.
- Untreated patients with primary central nervous system lymphoma (PCNSL) confirmed by pathology (immunotyping) according to the 2016 WHO classification of lymphoid neoplasms.
- Diffuse large B-cell lymphoma (DLBCL) originating from the central nervous system (CNS) without involvement of other organs, confirmed by PET-CT or contrast-enhanced CT.
- Expected survival greater than 3 months.
- Laboratory test results meeting all of the following:
Key exclusion criteria (12 listed)
- Contraindication to any drug included in the treatment regimen.
- History of clinically significant liver disease, including viral or other hepatitis or cirrhosis.
- Hepatitis B: Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV-DNA above ULN.
- Active hepatitis C: Positive HCV antibody with detectable HCV-RNA.
- Human Immunodeficiency Virus (HIV) infection.
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 |
|---|---|---|
| Zanubrutinib + Rituximab + MTX ± SelinexorThis is a single-arm interventional study. Participants will undergo an induction phase consisting of six 21-day cycles. During induction, all participants receive: Zanubrutinib 160 mg orally twice daily, Rituximab 375 mg/m² intravenous on Day 0, MTX 3.5 mg/m² intravenous on Days 1. Before the second treatment cycle, participants will be tested for TP53 mutation status. Participants who test positive for the TP53 mutation will receive Selinexor 40 mg orally on Days 1 weekly added to their treatment regimen. Following induction, participants enter a maintenance phase with: Zanubrutinib 160 mg orally twice daily, continued for up to 2 years or until disease progression or unacceptable toxicity. This design allows biomarker-driven treatment modification within a single treatment arm without randomization or separate comparator groups. | Drug | Single Arm: Zanubrutinib + Rituximab + MTX ± Selinexor |
Primary outcome
Complete Remission Rate (CRR)
Time frame: At the end of Cycle 6 and at 4 weeks after completion of Cycle 6 (each cycle is 21 days).
Complete Remission Rate (CRR) is defined as the proportion of participants achieving complete remission based on predefined hematologic and/or imaging criteria at the end of treatment Cycle 6.
1 secondary outcome
Overall Survival (OS)
Time frame: From initiation of study treatment to death from any cause or last follow-up, whichever occurs first, up to 2 years.
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 12 Feb 2026.
Related trials for Central Nervous System Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingPhase 1
Glofitamab With Obinutuzumab Pre-treatment for the Treatment of Central Nervous System Lymphoma
Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2
A Study of the Efficacy and Safety of Lisocabtagene Maraleucel (Liso-cel) as First-Line Therapy in Adults With Transplant-Ineligible Primary Central Nervous System Lymphoma
Lymphoma
Active, not recruitingPhase 1/2
Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment
Solid Tumor, Central Nervous System Tumor
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanubrutinib + Rituximab + MTX ± Selinexor in people with Central Nervous System Lymphoma, run by Ruijin Hospital at 1 site 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 11 inclusion and 12 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: opening soon, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Li Wang, Dr. (86-021-64370045-665257, wl_wangdong@126.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: At the end of Cycle 6 and at 4 weeks after completion of Cycle 6 (each cycle is 21 days).). 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 12 Feb 2026.