Zanubrutinib in Maintenance Therapy of DLBCL Patients With Initial Remission

NCT05596097 | Not Yet Recruiting Phase 2

• 1 other identifier: ZEBUBU22
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a single-center, single-arm, prospective clinical study to investigate the efficacy and safety of zanubrutinib maintenance therapy in patients with diffuse large B-cell lymphoma (DLBCL) in Initial remission. The patients were divided into two categories: 1) Zanubrutinib maintenance therapy was started after R-CHOP induction and consolidation therapy reached maximum efficacy; 2) Initiate zanubrutinib maintenance therapy after maximal response to induction and consolidation therapy with or without rituximab (R-chemo). Therefore, the data in this study will reflect the efficacy and safety of zanubrutinib in the maintenance treatment of DLBCL patients with initial remission, and will provide new insights into the clinical application of zanubrutinib.

Conditions

Diffuse Large B-cell Lymphoma (DLBCL)

Keywords

Diffuse Large B-cell Lymphoma (DLBCL); Maintenance Therapy; Zanubrutinib; Rituximab

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  EFS was defined as the time from initiation of zanubrutinib maintenance therapy to the occurrence of any event, including death, disease progression, change in chemotherapy regimen, change to chemotherapy, addition of other treatments, occurrence of fatal or intolerable side effects, etc. Whichever occurs first.

  up to 36 months

Secondary Outcomes (4)

• Conversion rate of partial response (PR) to CR

  up to 36 months

• Progression-free survival (PFS)

  up to 36 months

• Overall survival (OS)

  up to 36 months

• adverse event

  Adverse events were assessed during 3, 6, and 12 months after the start of zanubrutinib maintenance therapy and 6, 12, and 24 months after the end of treatment

Study Arms (1)

experimental group

EXPERIMENTAL

According to the initial treatment plan of the patients, the patients were divided into R-CHOP and R-chemo groups. Both groups received zanubrutinib 160 mg bid p.o. d1-28 maintenance treatment for 12 months after induction and consolidation therapy reached the maximum efficacy.

Drug: Zanubrutinib

Interventions

Zanubrutinib DRUG

Zanubrutinib, 180mg, bid, p.o., d1-28; Treatment cycles every 28 days

experimental group

Eligibility Criteria

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

You may qualify if:

• Patients with DLBCL who are diagnosed according to the 2021 NCCN Guidelines for B-cell Lymphoma, aged ≥18 years;
• Don't received treatment;
• Measurable lesions: at least 1 lymph node lesion \> 1.5 cm in longest dimension, or at least 1 extranodal lesion \> 1.0 cm in longest dimension, and at least 2 measurable lesions accurately measured vertical diameter;
• Clinical stage II (not suitable for local radiotherapy), III, IV (Ann Arbor stage); Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• Intermediate-high-risk /high-risk group: International Prognostic Index (IPI) score 3-5, aa-IPI score 2-3 or NCCN-IPI score ≥4;
• Expression of MYC, BCL-2 and BCL-6 (detected by immunohistochemistry, qualitative or quantitative detection), or MYD88, CD79A/CD79B \[9\] and TP53 genetic abnormality \[10\];
• Patients with non-bone marrow invasion:
• The absolute value of neutrophils≥1.5×109/L
• Platelets ≥100×109/L (judged by the investigator according to the condition, the minimum can be ≥75×109/L)
• Hemoglobin ≥ 90g/L;
• \. The level of biochemical indicators meets the following requirements:
• Renal function: endogenous creatinine clearance rate \> 30ml/min;
• Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal range (ULN); total bilirubin ≤ 2 × ULN (unless Gilbert syndrome is diagnosed);
• Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN; 9. life expectancy ≥ 3 months; 10. The patient and family members agree and sign an informed consent form.

You may not qualify if:

• Lymphoma with central nervous system invasion or mediastinal large B-cell lymphoma, diagnosis or treatment of malignant tumors other than DLBCL;
• Cannot tolerate zanubrutinib treatment, or have hypersensitivity reactions to any components of the study drug;
• Significant cardiovascular disease, including:
• Myocardial infarction within 6 months prior to screening;
• Unstable angina pectoris occurring within 3 months prior to screening;
• Clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);
• QTc (corrected by Fridericia formula): \>450ms in men, \>470ms in women, or other ECG abnormalities, including history of second-degree type II atrioventricular (AV) block or third-degree AV block;
• Any grade 3 or 4 heart disease as defined by the New York Heart Association (NYHA) functional class;
• Echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) ≤40% (AHA, 2022);
• Uncontrolled hypertension at screening, manifested as systolic blood pressure ≥180 mmHg and diastolic blood pressure ≥110 mmHg on at least two consecutive blood pressure measurements;
• Requires continuous treatment with strong or moderate CYP3A inhibitors/inducers. Patients are not eligible if they have taken strong or moderate CYP3A inhibitors/inducers within 7 days prior to the first dose of study drug (or have taken these drugs for less than 5 half-lives);
• Hepatitis B virus (HBV-DNA) ≥ 1x10\^3 copies/mL or HBV-DNA \> 200 IU/mL or active hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Serologically positive;
• Obvious bleeding tendency, such as a history of stroke, intracranial hemorrhage within 6 months, or a history of surgery within 4 weeks;
• Serious infectious diseases at the same time;
• Refuse to take reliable contraceptive methods during pregnancy, lactation or appropriate age;

Sponsors & Collaborators

• LanZhou University: lead
• BeOne Medicines: collaborator

Study Sites (1)

The First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

Location

Related Publications (6)

• Maurer MJ, Ghesquieres H, Jais JP, Witzig TE, Haioun C, Thompson CA, Delarue R, Micallef IN, Peyrade F, Macon WR, Jo Molina T, Ketterer N, Syrbu SI, Fitoussi O, Kurtin PJ, Allmer C, Nicolas-Virelizier E, Slager SL, Habermann TM, Link BK, Salles G, Tilly H, Cerhan JR. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014 Apr 1;32(10):1066-73. doi: 10.1200/JCO.2013.51.5866. Epub 2014 Feb 18.

  PMID: 24550425 BACKGROUND

• Yuan T, Zhang F, Yao Q, Liu Y, Zhu X, Chen P. Maintenance therapy for untreated diffuse large B-cell lymphoma: a systematic review and network meta-analysis. Ther Adv Hematol. 2021 May 29;12:20406207211018894. doi: 10.1177/20406207211018894. eCollection 2021.

  PMID: 34104373 BACKGROUND

• Pal Singh S, Dammeijer F, Hendriks RW. Role of Bruton's tyrosine kinase in B cells and malignancies. Mol Cancer. 2018 Feb 19;17(1):57. doi: 10.1186/s12943-018-0779-z.

  PMID: 29455639 BACKGROUND

• Tam CS, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, Owen RG, Marlton P, Wahlin BE, Sanz RG, McCarthy H, Mulligan S, Tedeschi A, Castillo JJ, Czyz J, Fernandez de Larrea C, Belada D, Libby E, Matous JV, Motta M, Siddiqi T, Tani M, Trneny M, Minnema MC, Buske C, Leblond V, Trotman J, Chan WY, Schneider J, Ro S, Cohen A, Huang J, Dimopoulos M. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstrom macroglobulinemia: the ASPEN study. Blood. 2020 Oct 29;136(18):2038-2050. doi: 10.1182/blood.2020006844.

  PMID: 32731259 BACKGROUND

• Byrd JC, Furman RR, Coutre SE, Burger JA, Blum KA, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Shaw Y, Bilotti E, Zhou C, James DF, O'Brien S. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015 Apr 16;125(16):2497-506. doi: 10.1182/blood-2014-10-606038. Epub 2015 Feb 19.

  PMID: 25700432 BACKGROUND

• Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. doi: 10.1182/bloodadvances.2021006083.

  PMID: 35390135 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bei Liu, MD

  The First Hospital of Lanzhou University,Lanzhou,Gansu,China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bei Liu, MD

CONTACT

+86 13809319379; liubeiff@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Clinical Professor，Deputy Director of Hematology Department

Model Details: According to the initial treatment plan of the patients, the patients were divided into R-CHOP and R-chemo groups. Both groups received zanubrutinib maintenance therapy after induction and consolidation therapy reached the maximum curative effect. With event-free survival (EFS) as the primary endpoint, partial remission (PR) to CR conversion rate, progression-free survival (PFS), and overall survival (OS) as secondary endpoints, adverse events (AEs) were assessed. ) incidence and related mechanisms during the study period.

Study Record Dates

• First Submitted: October 23, 2022
• First Posted: October 27, 2022
• Study Start: October 30, 2022
• Primary Completion: October 20, 2024
• Study Completion (Estimated): July 30, 2026
• Last Updated: October 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)