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

Sponsor

Ruijin Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05896007

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
PCNSL	Drug: Zanubrutinib Drug: Rituximab Drug: Methotrexate Drug: Temozolomide	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single Group AssignmentSingle Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

2-year Progression-Free Survival [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.

Secondary Outcome Measures

Overall Response Rate (ORR) [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).
Complete Response (CR) Rate [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).
Overall Survival (OS) [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.
Adverse Events [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18 to 80 years old;
Histopathologically confirmed CD20 positive primary large B-cell lymphoma of the central nervous system (CNS) according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours [previously named as primary difuse 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ruijin Hospital	Shanghai	Shanghai	China	20025

Sponsors and Collaborators

Ruijin Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zhao Weili, Professor, Ruijin Hospital

ClinicalTrials.gov Identifier:

NCT05896007

Other Study ID Numbers:

Zana

First Posted:

Jun 9, 2023

Last Update Posted:

Jun 9, 2023

Last Verified:

Jun 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Zhao Weili, Professor, Ruijin Hospital

PCNSL

zanubrutinib

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 9, 2023