NCT07185373

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

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

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 215 (estimated)
• Sponsor: Huashan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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).

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). 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 (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.

Conditions

• Primary Central Nervous System Lymphoma

Interventions

Type	Name	Description
DRUG	Teniposide	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.
DRUG	Orelabrutinib	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.
DRUG	MTX	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.
DRUG	Rituximab (R)	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.
DRUG	Dexamethasone	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.

Timeline

• Start date: 2025-10-01
• Primary completion: 2028-09-30
• Completion: 2029-07-30
• First posted: 2025-09-22
• Last updated: 2025-09-22

Locations

2 sites across 1 country: China