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

Sponsor
Huashan Hospital
Study ID
NCT07185373
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

  • Primary Central Nervous System Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

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.
  • 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.
  • 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.
  • 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.
  • 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.

Study Details

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).

Key Dates

First listed
Sep 22, 2025
Start date
Oct 1, 2025
Status verified
Aug 2026
Primary completion
Sep 30, 2028
Completion
Jul 30, 2029

Study Design

Enrollment
215 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A
    Teniposide, orelabrutinib, rituximab, methotrexate (MTX), and dexamethasone (21-day cycle).
  • Experimental: Arm B
    Orelabrutinib, rituximab, MTX and dexamethasone (21-day cycle).
  • Active Comparator: Arm C
    Rituximab, MTX and dexamethasone (21-day cycle)

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) ]

Central Contacts

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