Orelabrutinib,Rituximab and Methotrexate in Newly-diagnosed Primary Central Nervous System Lymphoma(PCNSL)

Study Overview
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Brief Summary
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This is a prospective single arm,multi-center,phase 2 study,and this study is to evaluate the efficacy and safety of Orelabrutinib,Rituximab combined with high-dose Methotrexate(RMO) as first line regimens in the treatments of newly diagnosed primary central nervous system lymphoma(PCNSL).Objective response and complete response are the primary endpoint.

Detailed Description
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This is a single-arm,multicenter,phase 2 study to evaluate the efficacy and safety of Orelabrutinib,Rituximab combined with high-dose Methotrexate(RMO) as first line regimens in the treatments of newly diagnosed primary central nervous system lymphoma.The response will be evaluated every 2 cycles.Patients who achieved complete remission(CR) or partial remission(PR) will receive further treatment,and there are 6 cycles of RMO regimen for the induction.The patients with stable disease(SD) or progressed disease(PD) will withdraw from the trial and receive salvage regimens.After total 6 induction cycles,the investigators evaluate the efficiency again.After 6 cycles,the patients who receive CR or PR,can tolerate Autologous Hematopoietic Stem Cell Transplantation(AHSCT) will be candidates of high-dose chemotherapy and stem rescue.The patients who achieve CR or PR,cannot tolerate AHSCT will go to whole brain radiotherapy or Orelabrutinib maintenance.The patients with SD or PD will receive salvage regimen.

Official Title
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a Single Arm,Multi-center,Phase II Clinical Trial of Combined Therapy for Orelabrutinib,Rituximab and Methotrexate(RMO)in Newly-diagnosed Primary Center Nervous System Lymphoma(PCNSL)

Conditions
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Primary Central Nervous System Lymphoma

Intervention / Treatment
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* Drug: Orelabrutinib,Rituximab and Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: primary central nervous system diffuse large B-cell lymphoma histologically confirmed by brain biopsy; Aged 18-70 years Signature of informed consent; At least one measurable lesion; Neutropile≥1.5X109/L,Hemoglobin≥80g/L,Platelets≥75X109/L,Billrubin<2XULN,ALT<4XULN,AST4XULN The expected survival time is at least 3 months Exclusion Criteria: Those who have contraindications to any of the components in the Orelabrutinib,Rituximab and HD-MTX History of other malignancies that may affect the compliance of the research protocol or the analysis of the results Severe cardiac insufficiency Other antitumor treatments were used Human immunodeficiency virus(HIV)antibody is positive Pregnant or lactating women Researchers consider if anyone not suitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orelabrutinib,Rituximab and Methotrexate<br>Rituximab 375 mg/m2 d1; MTX 3.5mg/m2,d2; Orelabrutinib 150g/day; every three week/cycle. | Drug: Orelabrutinib,Rituximab and Methotrexate<br>* Orelabrutinib, Rituximab combined with high-dose Methotrexate(RMO) as first line regimens in the treatments of newly diagnosed primary central nervous system lymphoma. The response will be evaluated every 2 cycles. Patients who achieved complete remission (CR) or partial remission (PR) will receive further treatment, and there are 6 cycles of RMO regimen for the induction. The patients with stable disease (SD) or progressed disease(PD) will withdraw from the trial and receive salvage regimens. After total 6 induction cycles, the investigators evaluate the efficiency again. After 6 cycles, the patients who receive CR or PR, can tolerate Autologous Hematopoietic Stem Cell Transplantation (AHSCT) will be candidates of high-dose chemotherapy and stem rescue. The patients who achieve CR or PR, cannot tolerate AHSCT will go to whole brain radiotherapy or Orelabrutinib maintenance. The patients with SD or PD will receive salvage regimen.<br>* Other names: RMO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| primary endpoint | Objective response rate(ORR) is the primary endpoint | Enrollment is expected to last for two year, followed up for five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| secondary endpoints | Complete rate(CR)、progression free survival(PFS)、overall survival(OS) are the secondary endpoints | Enrollment is expected to last for two year, followed up for five years |