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

NCT07185373 | Not Yet Recruiting Phase 2

• 1 other identifier: KY2025-725
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 2

Brief 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. Induction regimens: 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).

Conditions

Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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

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

• 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

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

Secondary Outcomes (3)

• Overall response rate (ORR) during induction therapy

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

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

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

• Progression-free survival (PFS)

  2 years after Day 1 Cycle 1

Study Arms (3)

Arm A

EXPERIMENTAL

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

Drug: Teniposide; Drug: Orelabrutinib; Drug: MTX; Drug: Rituximab (R); Drug: Dexamethasone

Arm B

EXPERIMENTAL

Orelabrutinib, rituximab, MTX and dexamethasone (21-day cycle).

Drug: Orelabrutinib; Drug: MTX; Drug: Rituximab (R); Drug: Dexamethasone

Arm C

ACTIVE COMPARATOR

Rituximab, MTX and dexamethasone (21-day cycle)

Drug: MTX; Drug: Rituximab (R); Drug: Dexamethasone

Interventions

Teniposide 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.

Arm A

Orelabrutinib 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.

Arm A; Arm B

MTX 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.

Arm A; Arm B; Arm C

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.

Arm A; Arm B; Arm C

Dexamethasone 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.

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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).
• 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
• 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.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (2)

West China Hospital of Sichuan University

Chengdu, China

Location

Department of Hematology, Qilu Hospital of Shandong University

Jinan, China

Location

MeSH Terms

Interventions

Teniposide; orelabrutinib; Rituximab; Dexamethasone

Intervention Hierarchy (Ancestors)

Glucosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Tong Chen

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tong Chen

CONTACT

+86-021-52887102; chentong@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 22, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): July 30, 2029
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

CN (2)