A Clinical Study Evaluating the Safety and Efficacy of ZRMT Regimen in the Treatment of PCNSL

NCT06445257 | Recruiting

• 1 other identifier: KY-2023-044-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, multicenter, open-label, single-arm clinical trial evaluating the safety and efficacy of the ZRMT (Zanubrutinib-Rituximab-Methotrexate-Temozolomide) regimen in the treatment of primary central nervous system lymphoma (PCNSL) with diffuse large B-cell lymphoma. This study includes an induction phase for PCNSL ± ASCT and a sequential maintenance phase.

Conditions

Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (6)

• Overall response rate，ORR

  Refers to the proportion of patients whose tumor volume has decreased to a predetermined value and can be maintained for a minimum duration requirement

  The period of 1 year from the start of treatment.

• Complete response，CR

  refers to the time from the first assessment of CR or PR to the first assessment of PD or death for any reason

  The period of 1 year from the start of treatment

• Duration of response,DOR

  refers to the time from the first assessment of CR or PR to the first assessment of PD or death for any reason

  The period of 1 year from the start of treatment

• 1 Year-Overall survival,1y-OS

  refers to the proportion of patients who have not died within 1 year after the start of the first treatment.

  The period of 1 year from the start of treatment

• Progression-Free Survival,PFS

  refers to the proportion of patients who have not experienced disease progression or death within 1 year after the start of the first treatment

  The period of 1 year from the start of treatment

• Overall survival, OS

  refers to the time from the start of the first treatment to death (for any reason)

  The period of 1 year from the start of treatment

Study Arms (1)

The ZRMT regimen is used to treat PCNSL

EXPERIMENTAL

zanubrutinib 160 mg BID orally rituximab: 375 mg/m2 intravenously on day 7, methotrexate: 3-3.5 g/m2 intravenously on day 1, and temozolomide 100 mg on days 1-5. Treatment will be given for 6-8 cycles, and patients who achieve a partial response (PR) or better can choose to undergo ASCT if they meet the transplantation criteria. After transplantation or for patients who do not undergo transplantation, zanubrutinib monotherapy maintenance treatment will be administered at a dose of 160 mg BID orally for 2 years or until disease progression, death, or intolerable adverse reactions.

Drug: zanubrutinib 160 mg BID orally

Interventions

zanubrutinib 160 mg BID orally DRUG

The ZRMT induction and maintenance regimen

Also known as: rituximab: 375 mg/m2 intravenously on day 7, methotrexate: 3-3.5 g/m2 intravenously on day 1, temozolomide 100 mg on days 1-5

The ZRMT regimen is used to treat PCNSL

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• According to the 2016 WHO classification of hematopoietic and lymphoid tissue tumors, the patient has been histopathologically diagnosed with primary central nervous system diffuse large B-cell lymphoma.
• Age ≥18 years and ≤75 years, any gender.
• Performance status score (ECOG): 0-1.
• Male participants and reproductive-age females must use contraception during the study and for 3 months after the last dose.
• Reproductive-age females must have a negative serum or urine pregnancy test at screening.
• Expected survival of more than 3 months.
• Laboratory tests must meet the following criteria:Hematology: Hemoglobin (Hb) ≥80 g/L, absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count (PLT) ≥75 × 109/L.Liver function: Serum total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤2.5 × ULN, alanine aminotransferase (ALT) ≤2.5 × ULN.Renal function: Creatinine clearance rate (Ccr) ≥50 mL/min.Coagulation function: International normalized ratio (INR) and prothrombin time (PT) ≤1.5 × ULN.Note: Patients who do not meet the above criteria may receive supportive treatment at the discretion of the investigator.
• The patient is aware of and voluntarily agrees to participate in the study and is able to comply with the scheduled visits and related procedures as specified in the protocol.

You may not qualify if:

• Patients who are determined by the investigator to be allergic, resistant, or intolerant to the drugs in the treatment regimen.
• Patients who have received any investigational drugs or radiation therapy within the past 4 weeks.
• Patients who have undergone major surgery within the past 4 weeks (excluding surgery related to the disease).
• Patients with severe infections within the past 4 weeks, as determined by the investigator, who are not suitable for treatment.
• Patients with a history of stroke or intracranial hemorrhage within the past 3 months, or active grade 3 or higher gastrointestinal bleeding.
• Patients who are pregnant or breastfeeding.
• Patients with impaired cardiac function or significant cardiac diseases, including but not limited to: a) myocardial infarction, congestive heart failure, or viral myocarditis within the past 6 months; b) symptomatic cardiac diseases requiring treatment intervention, such as unstable angina or arrhythmias; c) NYHA class II-IV heart function; d) echocardiographic ejection fraction (EF) below 50% or below the lower limit of the study center.
• Patients with a known history of human immunodeficiency virus (HIV) infection, primary immunodeficiency diseases, or active tuberculosis.
• Patients with poorly controlled hypertension or diabetes.
• Patients with active hepatitis B or hepatitis C infection (for HBsAg-positive or HBcAb-positive subjects, they can be included if HBV-DNA is not detected; for HCV antibody-positive subjects, they can be included if HCV-RNA is not detected).
• Patients with a history of malignant tumors that may affect the implementation of the trial protocol or result analysis (excluding cured basal cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, localized gastric or intestinal mucosal carcinoma, and localized prostate cancer).
• Patients with active mental disorders, alcoholism, drug abuse, or substance abuse.
• Patients who are determined by the investigator to be unsuitable for participation in this study.

Sponsors & Collaborators

• Huai'an First People's Hospital: lead
• Affiliated Hospital of Nantong University: collaborator
• The First People's Hospital of Changzhou: collaborator
• The Affiliated Hospital of Xuzhou Medical University: collaborator
• Northern Jiangsu People's Hospital: collaborator

Study Sites (1)

The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University（Huai'an First People's Hospital）

Huai'an, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Interventions

zanubrutinib; Rituximab; Methotrexate; Temozolomide

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Chunling Wang

CONTACT

15189552696; wcl6506@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 6, 2024
• Study Start: September 15, 2023
• Primary Completion: April 13, 2026
• Study Completion: April 30, 2026
• Last Updated: June 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)