R-MTX-zanbrutinib in Secondary CNS Lymphoma

NCT ID: NCT05398224

Last Updated: 2022-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-26

Study Completion Date

2024-05-26

Brief Summary

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Secondary central nervous system lymphoma (SCNSL) occurred in about 5% of patients with diffuse large B-cell lymphoma (DLBCL). The prognosis of SCNSL is very poor. A number of retrospective studies have shown that the median overall survival (mOS) since the diagnosis of CNSL is only 2.5-3.5 months, and the 2-year OS rate is only 20%. At present, there is no consensus on the treatment of SCNSL, and new therapeutic strategies are urgently needed. Zanubrutinib is a new second-generation BTK inhibitor, which has showed good efficacy and safety in a variety of B-NHL. Zanubrutinib has showed good blood-brain barrier permeability in preclinical studies. This study attempts to evaluate the efficacy and safety of zanubrutinib combined with rituximab and high-dose methotrexate in the treatment of SCNSL in patients with DLBCL.

Detailed Description

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Conditions

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Secondary Central Nervous System Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental arm: Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab

Zanubrutinib in combination with rituximab and methotrexate, followed by zanubrutinib maintenance in patients with secondary central nervous system lymphoma (SCNSL)

Group Type EXPERIMENTAL

Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab

Intervention Type DRUG

Induction therapy: Zanubrutinib will be given as 160mg bid orally between days 1 and 14 of each 14-day cycle; rituximab will be given at 375mg/m2 intravenously on day 1 of each cycle; methotrexate at 3.5g/m2 for patients ≤65 or 1.5g/m2 for patients \>65 (standard hydration/leucovorin support) will be given intravenously on day 2 of each 14-day cycle; for 6 cycles.

Consolidation therapy: For patients ≤65, autologous hematopoietic stem cell transplantation (ASCT with a conditioning regimen of thiotepa/carmustine) will be given as consolidation treatment after induction therapy.

Maintenance therapy:Drug: zanubrutinib. Zanubrutinib will be given as 160mg bid orally continuously until progression of the disease (PD), intolerable toxicity, death, or patient/investigator discretion.

Interventions

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Zanubrutinib, high-dose methotrexate (HD-MTX), rituximab

Induction therapy: Zanubrutinib will be given as 160mg bid orally between days 1 and 14 of each 14-day cycle; rituximab will be given at 375mg/m2 intravenously on day 1 of each cycle; methotrexate at 3.5g/m2 for patients ≤65 or 1.5g/m2 for patients \>65 (standard hydration/leucovorin support) will be given intravenously on day 2 of each 14-day cycle; for 6 cycles.

Consolidation therapy: For patients ≤65, autologous hematopoietic stem cell transplantation (ASCT with a conditioning regimen of thiotepa/carmustine) will be given as consolidation treatment after induction therapy.

Maintenance therapy:Drug: zanubrutinib. Zanubrutinib will be given as 160mg bid orally continuously until progression of the disease (PD), intolerable toxicity, death, or patient/investigator discretion.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Men and women ≥ 18, and ≤75 years of age
* Histologically documented systemic diffuse large B-cell lymphoma(DLBCL)
* Central nervous system (CNS) relapse (meningeal or /and intraparenchymal) with or without systemic lymphoma manifestations
* All patients need to have received at least one and ≤4 lines of prior therapy systemic lymphoma directed therapy.
* ECOG performance score 0-3
* Participants must have adequate bone marrow and organ function shown by:

* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥ 75 x 109/L(≥ 50 x 109/L if bone marrow involvement)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal, total bilirubin ≤ 2 times the upper limit of normal
* International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal
* serum creatinine (mg/dL)) ≤ 1.5 times the upper limit of normal ; calculated creatinine clearance(CrCl) ≥ 40ml/min using the Cockcroft-Gault equation
* Expected survival greater than 3 months
* Did not receive targeting agents within 10 days or receive chemortherapy, radiotherapy, or monoclonal antibody within 3 weeks
* Woman of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 30 days after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 3 months after the last dose
* Ability of participants or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document

Exclusion Criteria

* Newly diagnosed DLBCL with CNS involvement
* Previous treatment with Bruton's Tyrosine Kinase (BTK) inhibitors
* Received targeting agents within 10 days or received chemortherapy, radiotherapy, or monoclonal antibody within 3 weeks
* Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening
* History of severe bleeding diseases
* Patient is using warfarin or any other Coumadin-derivative anticoagulant or vitamin K antagonists. Patients must be off warfarin-derivative anticoagulants for at least seven days prior to starting the study drug. Low molecular weight heparin is allowed. Patients with congenital bleeding diathesis are excluded
* Patient is taking a drug known to be a moderate and strong inhibitor or inducers of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers for at least two weeks prior to starting the study drug
* Patient is known to have human immunodeficiency virus (HIV) infection
* Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests
* Patient is known to have an uncontrolled active systemic infection
* Patients with serous cavity effustion
* Patient underwent major systemic surgery ≤ 4 weeks prior to starting the trial treatment or who has not recovered from the side effects of such surgery
* Women who are pregnant or nursing (lactating)
* The patient is unwell or unable to participate in all required study evaluations and procedures
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University

OTHER

Sponsor Role lead

Responsible Party

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Jun Zhu

professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lijuan Deng

Role: CONTACT

Phone: 0086-10-88196109

Email: [email protected]

Facility Contacts

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Jun Zhu

Role: primary

Yuqin Song

Role: backup

Other Identifiers

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20210218

Identifier Type: -

Identifier Source: org_study_id