Zillion: Zanubrutinib Combined With Chemotherapy for Newly Diagnosed CNS Lymphoma

ConditionCentral Nervous System Lymphoma

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-80

SponsorRuijin Hospital

About this trial

Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. After the results of the second-generation sequencing were reported, selinisol was added to the original treatment plan for those with TP53 mutations, and the original treatment plan was continued for those without TP53 mutations. Each course of treatment lasts for three weeks. A mid-term assessment is conducted after three courses of treatment, and a final assessment is carried out after six courses of treatment. After the mid-term or final assessment:

If the PR is not achieved or the disease progresses at any time, the subjects are withdrawn from the group and receive salvage treatment.

If the subjects achieve CR or PR, they enter maintenance treatment and continue with zanubrutinib for 2 years. For young patients (\< 65 years old), they can choose whether to receive ASCT as consolidation treatment according to their personal will, and then follow up and observe until 3 years have passed.

SD/PD patients receive subsequent treatment after being judged by the researchers

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Have a full understanding of this study and voluntarily sign the informed consent form.

Untreated patients with primary central nervous system lymphoma (PCNSL) confirmed by pathology (immunotyping) according to the 2016 WHO classification of lymphoid neoplasms.

Diffuse large B-cell lymphoma (DLBCL) originating from the central nervous system (CNS) without involvement of other organs, confirmed by PET-CT or contrast-enhanced CT.

Expected survival greater than 3 months.

Disqualifiers

Contraindication to any drug included in the treatment regimen.

History of clinically significant liver disease, including viral or other hepatitis or cirrhosis.

Hepatitis B: Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV-DNA above ULN.

Active hepatitis C: Positive HCV antibody with detectable HCV-RNA.

Trial design

Design model

Single group

Treatments tested in this trial

Zanubrutinib + Rituximab + MTX ± Selinexor
Drug
This is a single-arm interventional study. Participants will undergo an induction phase consisting of six 21-day cycles. During induction, all participants receive: Zanubrutinib 160 mg orally twice daily, Rituximab 375 mg/m² intravenous on Day 0, MTX 3.5 mg/m² intravenous on Days 1. Before the second treatment cycle, participants will be tested for TP53 mutation status. Participants who test positive for the TP53 mutation will receive Selinexor 40 mg orally on Days 1 weekly added to their treatment regimen. Following induction, participants enter a maintenance phase with: Zanubrutinib 160 mg orally twice daily, continued for up to 2 years or until disease progression or unacceptable toxicity. This design allows biomarker-driven treatment modification within a single treatment arm without randomization or separate comparator groups.

Treatment groups

19 Participants

are divided into 1 treatment group

Group A: Single Arm: Zanubrutinib + Rituximab + MTX ± SelinexorExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Complete Remission Rate (CRR)

Complete Remission Rate (CRR) is defined as the proportion of participants achieving complete remission based on predefined hematologic and/or imaging criteria at the end of treatment Cycle 6.

Time frame

At the end of Cycle 6 and at 4 weeks after completion of Cycle 6 (each cycle is 21 days).

Secondary outcomes

Overall Survival (OS)

Overall Survival (OS) is defined as the time from initiation of study treatment to death from any cause. Participants who are alive at the time of analysis will be censored at the date they were last known to be alive. OS will be summarized using the Kaplan-Meier method.

Time frame

From initiation of study treatment to death from any cause or last follow-up, whichever occurs first, up to 2 years.

Other outcomes

Number of participants with treatment-related Adverse Events (AEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Safety will be evaluated by monitoring and recording the number, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of participants experiencing treatment-related AEs will be summarized by frequency and grade.

Time frame

From initiation of study treatment through the end of treatment (up to 6 cycles; each cycle is 21 days).

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ruijin Hospital

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: