Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-03-31 @ 11:48 AM
Study NCT ID:
NCT07410520
Status:
RECRUITING
Last Update Posted:
2026-02-13
First Post:
2026-02-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PD-1 Inhibitor Combined With Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) for Newly Diagnosed PCNSL and SCNSL.
Sponsor:
The First Affiliated Hospital with Nanjing Medical University
Organization:
Study Overview
Official Title:
A Multicenter, Open-Label, Single-Arm, Prospective Clinical Study of PD-1 Inhibitor Combined With Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) in the Treatment of Newly Diagnosed Primary Central Nervous System Lymphoma (ND-PCNSL) and Secondary Central Nervous System Lymphoma (SCNSL)
Status:
RECRUITING
Status Verified Date:
2026-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a multicenter, open-label, single-arm, prospective clinical study of PD-1 inhibitor combined with rituximab, methotrexate, and orelabrutinib (PD-1i+RMO) in the treatment of newly diagnosed primary central nervous system lymphoma (ND-PCNSL) and secondary central nervous system lymphoma (SCNSL). The primary endpoint is 1-year progression-free survival (PFS).
Detailed Description:
Primary central nervous system lymphoma (PCNSL) is a B-cell non-Hodgkin lymphoma confined to the brain, spinal cord, cerebrospinal fluid, and/or eyes, with no evidence of systemic involvement. Patients with PCNSL have a poor prognosis, with a median survival of only 1-2 years. High-dose methotrexate (HD-MTX, \>3 g/m² body surface area) remains the cornerstone of induction therapy and is often combined with other blood-brain barrier-penetrating agents, such as cytarabine or temozolomide. Recently, the addition of Bruton's tyrosine kinase (BTK) inhibitors to induction chemotherapy has been shown to significantly improve both the overall response rate (ORR) and complete response rate (CRR) in newly diagnosed patients.
To further enhance the complete response rate in patients with newly diagnosed PCNSL (ND-PCNSL) and secondary central nervous system lymphoma (SCNSL), sustain long-term remission, and improve progression-free survival (PFS) and overall survival (OS) after consolidation and maintenance therapy, this study will conduct a multicenter, open-label, prospective, single-arm clinical trial entitled: "PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) for Newly Diagnosed PCNSL and SCNSL." The trial aims to evaluate the efficacy and safety of this combination regimen.
The PD-1i+RMO regimen is administered in 3-week cycles. After 4 cycles, disease assessment includes cranial MRI (non-contrast + contrast) and whole-body contrast-enhanced CT or PET/CT. Patients initially diagnosed via ophthalmologic examination will also undergo ophthalmic evaluation. Those with stable disease (SD) or progressive disease (PD) will discontinue the study, whereas patients achieving partial response (PR) or complete response (CR) will receive 4 additional cycles.
After completing all 8 cycles, cranial MRI (non-contrast + contrast) and PET/CT are repeated, with ophthalmologic follow-up if indicated. Patients with PR, SD, or PD after 8 cycles will exit the study. Those achieving CR will be evaluated by the investigators for autologous stem cell transplantation (ASCT) or whole-brain radiotherapy (WBRT), followed by a 2-year maintenance phase consisting of PD-1 inhibitor administered every 2 months in combination with orelabrutinib.
To further enhance the complete response rate in patients with newly diagnosed PCNSL (ND-PCNSL) and secondary central nervous system lymphoma (SCNSL), sustain long-term remission, and improve progression-free survival (PFS) and overall survival (OS) after consolidation and maintenance therapy, this study will conduct a multicenter, open-label, prospective, single-arm clinical trial entitled: "PD-1 Inhibitor Combined with Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) for Newly Diagnosed PCNSL and SCNSL." The trial aims to evaluate the efficacy and safety of this combination regimen.
The PD-1i+RMO regimen is administered in 3-week cycles. After 4 cycles, disease assessment includes cranial MRI (non-contrast + contrast) and whole-body contrast-enhanced CT or PET/CT. Patients initially diagnosed via ophthalmologic examination will also undergo ophthalmic evaluation. Those with stable disease (SD) or progressive disease (PD) will discontinue the study, whereas patients achieving partial response (PR) or complete response (CR) will receive 4 additional cycles.
After completing all 8 cycles, cranial MRI (non-contrast + contrast) and PET/CT are repeated, with ophthalmologic follow-up if indicated. Patients with PR, SD, or PD after 8 cycles will exit the study. Those achieving CR will be evaluated by the investigators for autologous stem cell transplantation (ASCT) or whole-brain radiotherapy (WBRT), followed by a 2-year maintenance phase consisting of PD-1 inhibitor administered every 2 months in combination with orelabrutinib.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: