Primary Central Nervous System Lymphoma (PCNSL)Phase 2NCT07839247
Zanubrutinib Plus Lenalidomide for Frail Elderly Patients With Newly Diagnosed PCNSL
A Phase 2 study testing Zanubrutinib and Lenalidomide in people with Primary Central Nervous System Lymphoma (PCNSL) and Zanubrutinib, run by Xiaohui Ren at 1 site in China.
Trial summary
This is a prospective, single-arm, phase II clinical study evaluating the efficacy and safety of Zanubrutinib (a BTK inhibitor) plus Lenalidomide (an immunomodulatory drug) in frail elderly patients with newly diagnosed primary central nervous system lymphoma (PCNSL). Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Primary Central Nervous System Lymphoma (PCNSL), Zanubrutinib, Lenalidomide
- What is being tested?
- Zanubrutinib and Lenalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 25 Sep 2026to 1 Aug 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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Age ≥ 70 years.
- patients classified as "Frail"according to the simplified Geriatric Assessment (sGA):
- --ADL ≤ 4 residual functions, or
- IADL ≤ 5 residual functions, or
- CIRS: ≥ 1 comorbidity of grade 3-4 or > 8 comorbidities of grade 2, or
- Age ≥ 80 years with "UNFIT" profile "UNFIT" profile: ADL = 5 residual functions or IADL = 6-7 residual functions, or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade 2.
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- Voluntary provision of written informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
- Considered able to safely undergo lumbar puncture.
- Life expectancy of ≥ 3 months, as judged by the investigator.
- Histologically confirmed diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system (CNS).
- Hematologic function: absolute neutrophil count ≥ 1.5 x 10^9/L, hemoglobin ≥ 90 g/L, and platelet count ≥ 80 x 10^9/L.
- Hepatic function: serum total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and serum alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x ULN.
- Renal function: creatinine clearance ≥ 30 mL/min, as estimated using the Cockcroft-Gault formula, or serum creatinine ≤ 1.5 x ULN.
- Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
- Female participants of childbearing potential must have a negative pregnancy test within 7 days before the first dose and agree not to donate oocytes for reproductive purposes throughout the treatment and follow-up periods. Their male sexual partners must use condoms during sexual intercourse.
- Male participants with female partners of childbearing potential must use condoms during sexual intercourse throughout the study and refrain from donating or cryopreserving sperm during this period.
- Participants with stable and adequately controlled comorbidities may be enrolled, including those with hypertension (blood pressure ≤ 160/100 mmHg), type 2 diabetes mellitus (HbA1c ≤ 8%), or mild coronary artery disease without myocardial infarction within the preceding 6 months.
Who cannot join
- Any disease or condition that may impair drug absorption (e.g., active inflammatory gastrointestinal disease, active gastric ulcer, chronic diarrhea, dysphagia, prior gastrectomy, gastroparesis, or short bowel syndrome).
- Known hypersensitivity to zanubrutinib, lenalidomide, or any excipient contained in either drug.
- Active bleeding within 1 month before treatment; a need for therapeutic anticoagulation during the study (e.g., warfarin or other vitamin K antagonists); or any condition associated with an increased risk of bleeding or coagulopathy (e.g., high-risk esophageal varices or active ulcer disease).
- High risk of thrombosis.
- Concurrent participation in another interventional clinical study (participation in noninterventional observational studies is permitted).
- Major surgery within 4 weeks before treatment or an incompletely healed surgical incision.
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- Treatment with systemic corticosteroids within 4 weeks before treatment.
- Another active malignancy or a history of another malignancy within 5 years before the initiation of study treatment, except for malignancies adequately treated with curative intent, such as basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast.
- Receipt of any vaccine, including but not limited to a vaccine against COVID-19, influenza, pneumonia, herpes zoster, or hepatitis B, within 4 weeks before the first dose.
- Requirement for treatment with a moderate or strong CYP3A4/5 inhibitor or inducer within 2 weeks before the first dose or during the study;
- Stroke or intracranial hemorrhage within 6 months before the first dose.
- Known liver disease, including but not limited to alcoholic liver disease, cirrhosis, active hepatitis B virus (HBV) infection (detectable HBV DNA), active hepatitis C virus (HCV) infection (detectable HCV RNA), or other active hepatitis. Participants with HBV DNA below the limit of detection or cured HCV infection are not excluded. Participants with HBV or HCV infection may be enrolled after antiviral therapy, provided that HBV DNA is below the limit of detection or HCV RNA is undetectable, as applicable.
- Active syphilis.
- Human immunodeficiency virus (HIV) infection
- Epstein-Barr virus (EBV) infection
- An active infection requiring systemic treatment or unexplained fever with a body temperature ≥ 38.5℃ within 1 week before treatment;
- Any of the following cardiac or cardiovascular criteria:
- （1）A heart rate-corrected QT interval calculated using Fridericia's formula (QTcF) > 470 ms in females or > 450 ms in males, or other risk factors for QT-interval prolongation or arrhythmic events (e.g., hypokalemia or a personal or family history of long QT syndrome); （2）A clinically significant arrhythmia or other cardiovascular disease requiring clinical intervention, including but not limited to acute myocardial infarction, unstable angina, or coronary artery bypass grafting within 6 months before treatment; congestive heart failure of New York Heart Association (NYHA) class II or higher; left ventricular ejection fraction (LVEF) < 50%; hypertension not controlled with medication (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg); atrial fibrillation of European Heart Rhythm Association (EHRA) class ≥ 2b; or primary cardiomyopathy.
- 18. Prior organ transplantation or allogeneic stem cell transplantation.
- 19. Prior or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, or radiation pneumonitis considered by the investigator to render the patient unsuitable for the study.
- 20. An autoimmune disease requiring systemic treatment within the previous 2 years.
- 21. Incomplete clinical data (e.g., no pathology report or inability to undergo MRI or PET/CT assessment).
- 22. Pregnant (positive pregnancy test before dosing) or breastfeeding.
- 23. Any other disease, psychiatric disorder, metabolic abnormality, physical examination finding, or clinically significant laboratory abnormality that, in the investigator's judgment, may compromise the participant's adherence to the study requirements, expose the participant to an unacceptable risk, interfere with the interpretation of the study results, or otherwise render the participant unsuitable for treatment with the study drugs.
- 24. Any other circumstance that, in the investigator's judgment, renders the patient unsuitable for participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Deparment of neurosurgery, Beijing tiantan hospital
Beijing, Beijing Municipality, 100070
Xiaohui Ren, MD, +86-010-59975567, xiaohuiren@mail.ccmu.edu.cn/xiaohuiren@aliyun.com
Haoyi Li, MD, +86-010-59975567, lee_627269051@163.com
About this study
Official title: Zanubrutinib Plus Lenalidomide for Frail Elderly Patients With Newly Diagnosed Primary CNS Lymphoma: a Prospective, Single-arm, Phase II Clinical Study
This is a prospective, single-arm, phase II clinical study evaluating the efficacy and safety of Zanubrutinib (a BTK inhibitor) plus Lenalidomide (an immunomodulatory drug) in frail elderly patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The study plans to enroll 33 patients who are aged ≥ 70 years and classified as frail, a population for whom standard first-line treatment regimens, high-dose methotrexate-based chemotherapy, may be "unfit". This study includes screening phase, induction phase, consolidation phase and maintenance phase. The screening period is defined as within 1 week prior to the first dose. During induction, participants will receive Zanubrutinib 160 mg orally twice daily continuously and Lenalidomide 25 mg orally once daily on days 1-21 of each 28-day cycle for three cycles. Participants who achieve a partial response (PR) or complete response (CR) after induction will receive three additional 28-day consolidation cycles of the same regimen. Participants who achieve a CR after consolidation will continue maintenance treatment with Zanubrutinib and Lenalidomide until disease progression. Treatment response will be assessed throughout the study using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria and assessed every 3 months. The primary endpoint is the complete response rate (CRR) at the end of induction therapy. Secondary endpoints include overall response rate (ORR) at the end of induction therapy, CRR and ORR at the end of consolidation therapy, One-year and two-year progression-free survival (PFS) rates, Duration of response (DOR), overall survival (OS), adverse event (AE) and serious adverse event (SAE). Exploratory liquid-biopsy analyses will be performed to evaluate treatment response and prognosis.
- Conditions
- Primary Central Nervous System Lymphoma (PCNSL), Zanubrutinib, Lenalidomide, Frail Elderly
- Being tested
- Zanubrutinib, Lenalidomide
- Keywords
- primary central nervous system lymphoma, elderly, frail, zanubrutinib, lenalidomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
Zanubrutinib will be administered orally at 160 mg twice daily. Each treatment cycle will last 28 days. Induction phase: Induction treatment will consist of three cycles. Consolidation phase: Patients who achieve a partial response (PR) or complete response (CR) after induction treatment will proceed to consolidation treatment. Consolidation treatment will consist of three cycles. Maintenance phase: Patients who achieve a CR after consolidation will proceed to maintenance treatment.
LenalidomideDrug
Lenalidomide will be administered orally at 25 mg once daily on days 1-21 of each cycle. Each treatment cycle will last 28 days. Induction phase: Induction treatment will consist of three cycles. Consolidation phase: Patients who achieve a partial response (PR) or complete response (CR) after induction treatment will proceed to consolidation treatment. Consolidation treatment will consist of three cycles. Maintenance phase: Patients who achieve a CR after consolidation will proceed to maintenance treatment.
| Study group | Role | What they receive |
|---|---|---|
| Zanubrutinib plus lenalidomide | Experimental | Not described Receives: Drug: Zanubrutinib; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRR
complete response rate
Measured: From the first day of treatment to the completion of induction treatment (3 months)
Secondary outcomes (8)
CRR
complete response rate
Measured: From the first day of treatment to the completion of consolidation treatment (6 months)
ORR
overall response rate
Measured: From the first day of treatment to the completion of induction treatment (3 months)
ORR
overall response rate
Measured: From the first day of treatment to the completion of consolidation treatment (6 months)
PFS
progression-free survival
Measured: 1-year and 2-year PFS rates, and the time interval from the start of treatment to tumor progression or death from any cause (up to 24 months).
DOR
Duration of response
Measured: Time from documentation of tumor response (CR or PR) to disease progression or death (up to 24 months).
OS
overall survival
Measured: The percentage of surviving patients out of the total number of included patients (specifically assessed as 1- and 2-year OS rate in study objectives) (up to 24 months).
AE
adverse event
Measured: From the first day of treatment until 30 days after the last treatment (up to 24 months)
SAE
serious adverse event
Measured: from the first day of treatment until 30 days after the last treatment (up to 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2026
- Study start25 Sep 2026 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System Lymphoma (PCNSL)Studies of the same condition, open and under way.
- 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
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiaohui Ren
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xiaohui Ren, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07839247
- Sponsor's protocol ID
- HK2026-4-KT-C0081
- Status last verified
- Sep 2026
- First submitted
- 12 Sep 2026
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared because the dataset contains sensitive clinical and genomic information, and the informed consent does not cover public data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zanubrutinib Plus Lenalidomide for Frail Elderly Patients With Newly Diagnosed Primary CNS Lymphoma: a Prospective, Single-arm, Phase II Clinical Study
- ClinicalTrials.gov ID
- NCT07839247
- Acronym / sponsor ID
- HK2026-4-KT-C0081
- Conditions
- Primary Central Nervous System Lymphoma (PCNSL), Zanubrutinib, Lenalidomide, Frail Elderly
- Keywords
- primary central nervous system lymphoma, elderly, frail, zanubrutinib, lenalidomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Xiaohui RenUniversity, hospital or other
- Study start
- 25 Sep 2026 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Aug 2029 (estimated)
- First posted
- 24 Sep 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, single-arm, phase II clinical study evaluating the efficacy and safety of Zanubrutinib (a BTK inhibitor) plus Lenalidomide (an immunomodulatory drug) in frail elderly patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The study plans to enroll 33 patients who are aged ≥ 70 years and classified as frail, a population for whom standard first-line treatment regimens, high-dose methotrexate-based chemotherapy, may be "unfit". This study includes screening phase, induction phase, consolidation phase and maintenance phase. The screening period is defined as within 1 week prior to the first dose. During induction, participants will receive Zanubrutinib 160 mg orally twice daily continuously and Lenalidomide 25 mg orally once daily on days 1-21 of each 28-day cycle for three cycles. Participants who achieve a partial response (PR) or complete response (CR) after induction will receive three additional 28-day consolidation cycles of the same regimen. Participants who achieve a CR after consolidation will continue maintenance treatment with Zanubrutinib and Lenalidomide until disease progression. Treatment response will be assessed throughout the study using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria and assessed every 3 months. The primary endpoint is the complete response rate (CRR) at the end of induction therapy. Secondary endpoints include overall response rate (ORR) at the end of induction therapy, CRR and ORR at the end of consolidation therapy, One-year and two-year progression-free survival (PFS) rates, Duration of response (DOR), overall survival (OS), adverse event (AE) and serious adverse event (SAE). Exploratory liquid-biopsy analyses will be performed to evaluate treatment response and prognosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zanubrutinib plus lenalidomide | Experimental | Drug: Zanubrutinib, Drug: Lenalidomide |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (18 listed)
- Age ≥ 70 years.
- patients classified as "Frail"according to the simplified Geriatric Assessment (sGA):
- --ADL ≤ 4 residual functions, or
- Voluntary provision of written informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
Key exclusion criteria (25 listed)
- Any disease or condition that may impair drug absorption (e.g., active inflammatory gastrointestinal disease, active gastric ulcer, chronic diarrhea, dysphagia, prior gastrectomy, gastroparesis, or short bowel syndrome).
- Known hypersensitivity to zanubrutinib, lenalidomide, or any excipient contained in either drug.
- Active bleeding within 1 month before treatment; a need for therapeutic anticoagulation during the study (e.g., warfarin or other vitamin K antagonists); or any condition associated with an increased risk of bleeding or coagulopathy (e.g., high-risk esophageal varices or active ulcer disease).
- High risk of thrombosis.
- Concurrent participation in another interventional clinical study (participation in noninterventional observational studies is permitted).
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 |
|---|---|---|
| ZanubrutinibZanubrutinib will be administered orally at 160 mg twice daily. Each treatment cycle will last 28 days. Induction phase: Induction treatment will consist of three cycles. Consolidation phase: Patients who achieve a partial response (PR) or complete response (CR) after induction treatment will proceed to consolidation treatment. Consolidation treatment will consist of three cycles. Maintenance phase: Patients who achieve a CR after consolidation will proceed to maintenance treatment. | Drug | Zanubrutinib plus lenalidomide |
| LenalidomideLenalidomide will be administered orally at 25 mg once daily on days 1-21 of each cycle. Each treatment cycle will last 28 days. Induction phase: Induction treatment will consist of three cycles. Consolidation phase: Patients who achieve a partial response (PR) or complete response (CR) after induction treatment will proceed to consolidation treatment. Consolidation treatment will consist of three cycles. Maintenance phase: Patients who achieve a CR after consolidation will proceed to maintenance treatment. | Drug | Zanubrutinib plus lenalidomide |
Primary outcome
CRR
Time frame: From the first day of treatment to the completion of induction treatment (3 months)
complete response rate
8 secondary outcomes
CRR
Time frame: From the first day of treatment to the completion of consolidation treatment (6 months)
ORR
Time frame: From the first day of treatment to the completion of induction treatment (3 months)
ORR
Time frame: From the first day of treatment to the completion of consolidation treatment (6 months)
PFS
Time frame: 1-year and 2-year PFS rates, and the time interval from the start of treatment to tumor progression or death from any cause (up to 24 months).
DOR
Time frame: Time from documentation of tumor response (CR or PR) to disease progression or death (up to 24 months).
OS
Time frame: The percentage of surviving patients out of the total number of included patients (specifically assessed as 1- and 2-year OS rate in study objectives) (up to 24 months).
AE
Time frame: From the first day of treatment until 30 days after the last treatment (up to 24 months)
SAE
Time frame: from the first day of treatment until 30 days after the last treatment (up to 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 28 Sep 2026.
- Individual participant dataSharing planned: No. IPD will not be shared because the dataset contains sensitive clinical and genomic information, and the informed consent does not cover public data sharing.
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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.
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 and Lenalidomide in people with Primary Central Nervous System Lymphoma (PCNSL) and Zanubrutinib, run by Xiaohui Ren 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 18 inclusion and 25 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 28 Sep 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 Xiaohui Ren, MD (+86-010-59975567, xiaohuiren@mail.ccmu.edu.cn/xiaohuiren@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRR (time frame: From the first day of treatment to the completion of induction treatment (3 months)). 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 28 Sep 2026.