Zanubrutinib Combined With Rituximab and Chemotherapy for Newly-Diagnosed PCNSLBCL Patients Intolerant to HSCT

September 1, 2023 updated by: Zhao Weili, Ruijin Hospital

Zanubrutinib Combined With Rituximab and Chemotherapy for Newly-Diagnosed Primary Central Nervous System Large B-Cell Lymphoma Patients Intolerant to Haematopoietic Stem Cell Transplantation

This single-center, open, single-arm study aim to evaluate the efficacy and tolerability of a therapy introducing zanubrutinib on the basis of rituximab and methotrexate (MTX) [or temozolomide (TMZ), if intolerant to MTX] in treating patients newly diagnosed with primary CNS large B-cell lymphoma and intolerant to HSCT.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Participants will receive zanubrutinib in addition to first-line therapy consisting of rituximab and either MTX or TMZ. After treatment of 6 cycles with the new regimen, the patients achieving CR or PR would go on to receive zanubrutinib maintenance of 1 year (if tolerable).

Study Type

Interventional

Enrollment (Estimated)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 20025

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 18 to 80 years old;
  • Histopathologically confirmed CD20 positive primary large B-cell lymphoma of the central nervous system (CNS) or primary vitreoretinal lymphoma according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours [primary large B-cell lymphoma of the CNS previously named as primary diffuse large B-cell lymphoma (DLBCL) of the CNS in the revised 4th edition];
  • Life expectancy of > 3 months (in the opinion of the investigator);
  • Creatinine Clearance Rate (CCR) ≥ 50 mL/min or estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/(min·1.73 m^2);
  • International Normalized Ratio (INR) ≤ 1.5 and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 times the upper limit of normal;
  • Left Ventricular Ejection Fraction (LVEF) ≥ 50%;
  • Agreeing to provide written informed consent prior to any special examination or procedure for the research on their own or legal representative.

Exclusion Criteria:

  • Pregnant or lactating women;
  • Known Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection (HBV infection refers to HBV-DNA > detectable limit);
  • With acquired or congenital immunodeficiency;
  • With congestive heart failure in 6 months before enrollment, New York Heart Association (NYHA) heart function class III or IV, or LVEF < 50%;
  • Known to be allergic to the test drug ingredients;
  • Diagnosed with or being treated for malignancy other than lymphoma;
  • With severe infection;
  • Substance abuse, medical, psychological, or social conditions that may interfere with the subjects' participation in the study or evaluation of the study results;
  • Deemed unsuitable for the group.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ZR-chemo
Drug: Zanubrutinib, Rituximab and MTX (or TMZ, if intolerant to MTX)
Drug: Zanubrutinib
160 mg bid po, until disease progression, intolerance of drug toxicity or death, otherwise maintaining during the 1st year in 2 years of follow-up
Other Names:
  • brukisa
Drug: Rituximab
375 mg/m^2 ivgtt, D0 of each 28-day cycle
Drug: Methotrexate
3.5 g/m^2 ivgtt, D1 of each 28-day cycle
Drug: Temozolomide
150 mg/m^2 ivgtt, D1-D5 of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year Progression-Free Survival
Time Frame: 2 years
Progression-free survival was defined as the time from the date of first treatment until the date of the first documented day of disease progression or relapse, according to 2014 Lugano criteria, or death from any cause, whichever occurred first.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
The ORR is defined as percentage of participants with overall response including complete response (CR), unconfirmed complete response (CRu) and partial response (PR), on the basis of investigator assessments, according to the 2005 Response Criteria of the International Primary CNS Lymphoma Collaborative Group (IPCG).
Baseline up to data cut-off (up to approximately 2 years)
Complete Response (CR) Rate
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
The CR rate is defined as the proportion of patients with CR/CRu according to the 2005 Response Criteria of the International Primary CNS Lymphoma Collaborative Group (IPCG).
Baseline up to data cut-off (up to approximately 2 years)
Overall Survival (OS)
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
Overall survival is defined as the time from the date of first treatment to the date of death from any cause.
Baseline up to data cut-off (up to approximately 2 years)
Adverse Events
Time Frame: Baseline up to data cut-off (up to approximately 2 years)
Any harmful reaction that occurs during the treatment of a disease according to the normal usage and dosage of a drug, which is unrelated to the purpose of treatment.
Baseline up to data cut-off (up to approximately 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

May 1, 2023

First Submitted That Met QC Criteria

June 8, 2023

First Posted (Actual)

June 9, 2023

Study Record Updates

Last Update Posted (Actual)

September 5, 2023

Last Update Submitted That Met QC Criteria

September 1, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Zana

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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