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Primary Central Nervous System LymphomaPhase 2/3NCT07185373

Orelabrutinib Combined With Teniposide, Rituximab and Methotrexate for Newly Diagnosed PCNSL

A Phase 2/3 study testing Teniposide, Orelabrutinib and MTX in people with Primary Central Nervous System Lymphoma, run by Huashan Hospital at 15 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a three-arm, multicenter, randomized controlled trial. Eligible participants will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Primary Central Nervous System Lymphoma
What is being tested?
Teniposide, Orelabrutinib and MTX
Could I receive a placebo?
No, everyone receives an active treatment
How many people
215 participants
Where
15 sitesChina
Study dates
1 Oct 2025to 30 Jul 2029
Phase
Phase 2/3
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • No prior systemic treatment for primary central nervous system lymphoma
  • Pathologically confirmed as diffuse large B-cell lymphoma subtype; with sufficient residual surgical specimens remaining after meeting the needs for pathological diagnosis and preservation
  • Aged 18-75 years (inclusive)
  • ECOG performance status ≤3
  • Expected survival time exceeding 3 months
  • Major organ functions meeting the following standards:
Show all 12Show fewer
  • Blood routine parameters (without growth factor support or blood transfusion within the past 7 days; 14 days for pegylated myeloid growth factors): absolute neutrophil count (ANC) ≥1.0×10⁹/L, platelet count (PLT) ≥75×10⁹/L, hemoglobin (Hb) ≥80g/L;
  • Blood biochemistry: total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) or ≤3×ULN (for confirmed Gilbert syndrome with direct bilirubin within normal range); aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5×ULN; serum creatinine within normal range; estimated glomerular filtration rate (eGFR) ≥70ml/min;
  • Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN;
  • Ability to tolerate lumbar puncture and/or having an indwelling Ommaya reservoir
  • Peripheral blood flow cytometry showed no clonal B cells and no other extramedullary lesions.
  • Voluntary signing of a written informed consent form by the participant or their legal representative prior to trial screening, indicating their understanding of the study purpose, necessary procedures, and willingness to comply with the protocol and attend follow-up visits

Who cannot join

  • Lymphoma involving sites outside the central nervous system (CNS)
  • Patients with a previous history of tumors
  • Patients with intraocular lymphoma or suspected diagnosis of intraocular lymphoma invasion
  • Uncontrolled or significant cardiovascular diseases, including:
  • New York Heart Association (NYHA) class Ⅲ-Ⅳ congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first administration of study drugs; clinically significant or treatment-requiring arrhythmias at screening; left ventricular ejection fraction (LVEF) <50%; or patients with controlled coronary heart disease who are either not using anticoagulants/antiplatelet drugs or taking 2 or more anticoagulants/antiplatelet drugs orally.
  • Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy).
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  • A history of clinically significant QTc interval prolongation, or QTc interval (calculated via Bazett's formula using manually collected screening data) >470ms in females or >450ms in males.
  • Refractory hypertension (blood pressure not controlled despite ≥1 month of optimal, tolerable doses of 2 or more antihypertensive drugs [including diuretics] with lifestyle modifications; or blood pressure controlled only with 3 or more antihypertensive drugs).
  • Active bleeding within 2 months prior to screening; use of anticoagulants/antiplatelet drugs for <6 months; or a definite bleeding tendency as judged by the investigator (e.g., bleeding-risk esophageal varices, active local ulcer lesions).
  • Diabetic patients whose blood sugar remains poorly controlled after insulin treatment
  • A history of stroke or intracranial hemorrhage within 6 months prior to screening, excluding postoperative sequelae-related intracranial hemorrhage
  • A history of organ transplantation or allogeneic bone marrow transplantation
  • Surgical procedures within 6 weeks prior to screening (diagnostic examinations are not considered surgical procedures; insertion of vascular access devices is exempt from this exclusion criterion).
  • Use of Chinese herbal medicines with anti-tumor effects (as specified in the package insert, e.g., Compound Cantharidin Capsules) within 4 weeks prior to screening
  • Active or uncontrolled hepatitis B virus (HBV) infection (HBsAg positive and/or HBcAb positive with positive HBV DNA titer); HCV Ab positive; HIV positive. The following patients can be provisioned for continuous observation pending enrollment when given prophylactic anti-HBV (such as entecavir or tenofovir), including :
  • HBsAg positive with negative HBV DNA titer.
  • HBsAg negative, HBsAb negative, HBcAb positive, and negative HBV DNA titer Patients with positive HBV-DNA can be considered for enrollment only when the HBV-DNA value is less than 500IU/mL after treatment
  • Uncontrolled active systemic fungal, bacterial, viral, or other infections (defined as persistent infection-related symptoms/signs that do not improve despite appropriate antibiotic or other treatments) or requiring intravenous antibiotics
  • Administration of live vaccines or immunological agents within 4 weeks prior to enrollment.
  • Need for concurrent and continuous use of drugs with moderate/strong inhibitory or inductive effects on cytochrome P450 CYP3A.
  • Patients with hypersensitivity to orelabrutinib or its excipients (e.g., immediate or accelerated allergic reactions).
  • Patients with hypersensitivity to teniposide or its excipients (e.g., immediate or accelerated allergic reactions)
  • Clinically significant gastrointestinal abnormalities that may affect drug intake, transit, or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or participants with total gastrectomy.
  • Participants with a history or current presence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia with severely impaired lung function, etc
  • Participants with chronic liver damage, severe fatty liver, or alcoholic liver disease.
  • Pregnant or lactating women; women of childbearing age who are unwilling to use contraception from the time of enrollment until 180 days after the last dose of the study drug (serum pregnancy test results must be negative within 14 days before the start of study drug treatment for women of childbearing potential); men who are not surgically sterilized and unwilling to use contraception during the study and until 180 days after the last dose of the study drug.
  • Presence of life-threatening diseases or severe organ dysfunction, deemed unsuitable for participation in the trial by the investigator.
  • Any mental or cognitive impairment that may limit the understanding and execution of the informed consent form or adherence to the study
  • Previous receipt of whole-brain radiotherapy for primary central nervous system lymphoma.

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

15 sites in 1 country

China15 sites, 15 recruiting
  • Peking University Third Hospital

    Beijing

    Hongmei Jing

    Not yet recruiting
  • Xuanwu Hospital

    Beijing

    Wanling Sun

    Recruiting
  • Huaxi Hospital

    Chengdu

    ming jiang

    Recruiting
  • First Affiliated Hospital of Fujian Medical University

    Fuzhou

    Ting Yang

    Not yet recruiting
  • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

    Guangzhou

    Yudan Wu

    Not yet recruiting
  • Department of Hematology, Qilu Hospital of Shandong University

    Jinan

    jingjing ye

    Recruiting
  • The First Affiliated Hospital of Nanchang University

    Nanchang

    Fei Li

    Recruiting
  • The Tumor Hospital of Jiangsu Province

    Nanjing

    Jianqiu Wu

    Not yet recruiting
  • Changhai Hospital

    Shanghai

    Xiong Ni

    Not yet recruiting
  • Huashan Hospital

    Shanghai

    Tong Chen

    Recruiting
  • RenJi Hospital

    Shanghai

    Honghui Huang

    Not yet recruiting
  • Shanghai Tongji Hospital, Tongji University School of Medicine

    Shanghai

    Bing Xiu

    Recruiting
  • WuhanUnionHospital

    Wuhan

    Jun Fang

    Recruiting
  • Tang-Du Hospital

    Xi'an

    Weiwei Qin

    Recruiting
  • Henan Cancer Hospital

    Zhengzhou

    Keshu Zhou

    Recruiting

Other trials in China

About this study

Official title: Orelabrutinib Combined With Teniposide, Rituximab and Methotrexate for Newly Diagnosed Primary Central Nervous System Lymphoma-A Randomized Controlled Trial

This is a three-arm, multicenter, randomized controlled trial. Eligible participants will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio.

Induction regimens:

Read more

Arm A: Teniposide + orelabrutinib + rituximab + methotrexate (MTX) + dexamethasone, administered in 21-day cycles.

Arm B: Orelabrutinib + rituximab + MTX + dexamethasone, administered in 21-day cycles.

Arm C: Rituximab + MTX + dexamethasone, administered in 21-day cycles. Participants achieving complete response (CR) or unconfirmed complete response (CRu) post-induction will proceed to consolidation therapy, with options including: MTX + rituximab (once every 3 months for 1 year); high-dose chemotherapy followed by autologous stem cell transplantation (ASCT); dose-reduced whole brain radiotherapy; or other modalities (as determined by the investigator).

Read the detailed description

This is a three-arm, multicenter, randomized controlled trial. Eligible participants (meeting inclusion and exclusion criteria) will be assigned to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Stratification will be based on two factors: age (≤60 vs. >60 years) and ECOG performance status (0-1 vs. 2-3).

Induction regimens:

Arm A: Teniposide, orelabrutinib, rituximab, methotrexate (MTX) and dexamethasone (21-day cycle).

Arm B: Orelabrutinib, rituximab, MTX and dexamethasone (21-day cycle). Arm C: Rituximab, MTX and dexamethasone (21-day cycle).

Following induction therapy, participants achieving complete response (CR) or unconfirmed complete response (CRu) will receive consolidation therapy. Four options are available, with selection determined by investigators based on individual patient conditions in real-world practice:

Chemotherapy (MTX + rituximab, administered once every 3 months for 1 year); High-dose chemotherapy conditioning followed by autologous stem cell transplantation (ASCT); dose-reduced whole brain radiotherapy; Other consolidation modalities. Participants who do not achieve CR or CRu after induction therapy will be eligible for alternative anti-primary central nervous system lymphoma (anti-PCNSL) treatments, as determined by investigators based on individual clinical status.

Being tested
Teniposide, Orelabrutinib, MTX, Rituximab (R), Dexamethasone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TeniposideDrug

    This trial enrolls eligible participants (meeting inclusion and exclusion criteria), who will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Stratification factors include age (≤60 vs. >60 years) and ECOG performance status (0-1 vs. 2-3). Within each stratum, blocks of size 15 will be used to ensure balanced allocation.

    Induction regimens:

    Arm A: Teniposide, orelabrutinib, rituximab, methotrexate (MTX) and dexamethasone, administered in 21-day cycles.

    Arm B: Orelabrutinib, rituximab, MTX and dexamethasone, administered in 21-day cycles.

    Arm C: Rituximab, MTX and dexamethasone, administered in 21-day cycles. Following induction therapy, participants achieving complete response (CR) or unconfirmed complete response (CRu) will proceed to consolidation therapy.

  • OrelabrutinibDrug

    This trial enrolls eligible participants (meeting inclusion and exclusion criteria), who will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Stratification factors include age (≤60 vs. >60 years) and ECOG performance status (0-1 vs. 2-3). Within each stratum, blocks of size 15 will be used to ensure balanced allocation.

    Induction regimens:

    Arm A: Teniposide, orelabrutinib, rituximab, methotrexate (MTX) and dexamethasone, administered in 21-day cycles.

    Arm B: Orelabrutinib, rituximab, MTX and dexamethasone, administered in 21-day cycles.

    Arm C: Rituximab, MTX and dexamethasone, administered in 21-day cycles. Following induction therapy, participants achieving complete response (CR) or unconfirmed complete response (CRu) will proceed to consolidation therapy.

  • MTXDrug

    This trial enrolls eligible participants (meeting inclusion and exclusion criteria), who will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Stratification factors include age (≤60 vs. >60 years) and ECOG performance status (0-1 vs. 2-3). Within each stratum, blocks of size 15 will be used to ensure balanced allocation.

    Induction regimens:

    Arm A: Teniposide, orelabrutinib, rituximab, methotrexate (MTX) and dexamethasone, administered in 21-day cycles.

    Arm B: Orelabrutinib, rituximab, MTX and dexamethasone, administered in 21-day cycles.

    Arm C: Rituximab, MTX and dexamethasone, administered in 21-day cycles. Following induction therapy, participants achieving complete response (CR) or unconfirmed complete response (CRu) will proceed to consolidation therapy.

  • Rituximab (R)Drug

    This trial enrolls eligible participants (meeting inclusion and exclusion criteria), who will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Stratification factors include age (≤60 vs. >60 years) and ECOG performance status (0-1 vs. 2-3). Within each stratum, blocks of size 15 will be used to ensure balanced allocation.

    Induction regimens:

    Arm A: Teniposide, orelabrutinib, rituximab, methotrexate (MTX) and dexamethasone, administered in 21-day cycles.

    Arm B: Orelabrutinib, rituximab, MTX and dexamethasone, administered in 21-day cycles.

    Arm C: Rituximab, MTX and dexamethasone, administered in 21-day cycles. Following induction therapy, participants achieving complete response (CR) or unconfirmed complete response (CRu) will proceed to consolidation therapy.

  • DexamethasoneDrug

    This trial enrolls eligible participants (meeting inclusion and exclusion criteria), who will be randomized to one of three induction regimens via stratified block randomization at a 2:2:1 ratio. Stratification factors include age (≤60 vs. >60 years) and ECOG performance status (0-1 vs. 2-3). Within each stratum, blocks of size 15 will be used to ensure balanced allocation.

    Induction regimens:

    Arm A: Teniposide, orelabrutinib, rituximab, methotrexate (MTX) and dexamethasone, administered in 21-day cycles.

    Arm B: Orelabrutinib, rituximab, MTX and dexamethasone, administered in 21-day cycles.

    Arm C: Rituximab, MTX and dexamethasone, administered in 21-day cycles. Following induction therapy, participants achieving complete response (CR) or unconfirmed complete response (CRu) will proceed to consolidation therapy.

Study groups in NCT07185373
Study groupRoleWhat they receive
Arm AExperimentalTeniposide, orelabrutinib, rituximab, methotrexate (MTX), and dexamethasone (21-day cycle).
Receives: Drug: Teniposide; Drug: Orelabrutinib; Drug: MTX; Drug: Rituximab (R); Drug: Dexamethasone
Arm BExperimentalOrelabrutinib, rituximab, MTX and dexamethasone (21-day cycle).
Receives: Drug: Orelabrutinib; Drug: MTX; Drug: Rituximab (R); Drug: Dexamethasone
Arm CActive comparatorRituximab, MTX and dexamethasone (21-day cycle)
Receives: Drug: MTX; Drug: Rituximab (R); Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of CR/CRu in Arm A versus Arm C during the induction therapy phase

    Efficacy evaluation will be determined in accordance with the IPCG criteria

    Measured: At the end of Cycle6 (each cycle is 21 days)

  2. The proportion of CR/CRu in Arm A versus Arm B during the induction therapy phase

    Efficacy evaluation will be determined in accordance with the IPCG criteria

    Measured: At the end of Cycle6 (each cycle is 21 days)

Secondary outcomes (3)
  1. Overall response rate (ORR) during induction therapy

    Efficacy evaluation will be determined in accordance with the IPCG criteria

    Measured: At the end of Cycle6 (each cycle is 21 days)

  2. proportion of CR/CRu in Arm B versus Arm C during the induction therapy phase

    Efficacy evaluation will be determined in accordance with the IPCG criteria

    Measured: At the end of Cycle6 (each cycle is 21 days)

  3. Progression-free survival (PFS)

    Efficacy evaluation will be determined in accordance with the IPCG criteria

    Measured: 2 years after Day 1 Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Sep 2025
  2. Study start1 Oct 2025
  3. Primary completion30 Sep 2028 (estimated)
  4. Study completion30 Jul 2029 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
215 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07185373
Sponsor's protocol ID
KY2025-725
Status last verified
Aug 2026
First submitted
11 Sep 2025
Last updated
19 Aug 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Teniposide, Orelabrutinib and MTX in people with Primary Central Nervous System Lymphoma, run by Huashan Hospital at 15 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 29 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 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Tong Chen (+86-021-52887102, chentong@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of CR/CRu in Arm A versus Arm C during the induction therapy phase (time frame: At the end of Cycle6 (each cycle is 21 days)). 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 19 Aug 2026.

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