- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05596097
Zanubrutinib in Maintenance Therapy of DLBCL Patients With Initial Remission
Clinical Research for Efficacy and Safety of Zanubrutinib in Maintenance Therapy of DLBCL Patients With Initial Remission
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive malignant lymphoma, and because it is sensitive to chemotherapy, approximately 50% to 70% of patients can achieve a cure after first-line treatment. However, in recent years, it has been found that more than 30% of patients experience relapse within two years after first-line treatment, which is a serious health threat and requires urgent secondary treatment. To reduce the recurrence of DLBCL and improve the survival rate of patients, clinical researchers have long been dedicated to the maintenance treatment of DLBCL patients after first-line treatment, aiming to kill tumor cells and reduce the risk of recurrence through continuous drug administration, thus enabling patients to survive with the tumor for a long time. Several clinical trials are currently underway with rituximab, ibrutinib, lenalidomide, and thalidomide, but safer and more effective maintenance regimens have yet to be identified.
Zanubrutinib, a new-generation BTK inhibitor, is the first anti-tumor drug developed locally in China and approved for marketing in the US. Zanubrutinib inhibits the activation of the BCR signaling pathway by specifically binding to cysteine residues at the active site of BTK to form a covalent bond that irreversibly inactivates them, thereby inhibiting BTK and improving the tumor microenvironment, inhibiting malignant proliferation and inducing apoptosis in tumor B cells. Several clinical studies have demonstrated that ibrutinib alone and in combination is no less effective than ibrutinib in the treatment of DLBCL, and has a better safety and tolerability profile.
This study proposes to use Zanubrutinib for maintenance treatment in DLBCL patients in remission after primary treatment and to evaluate the efficacy and safety of patients to provide new insights into the clinical use of Zanubrutinib.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Gansu
-
Lanzhou, Gansu, China, 730000
- The First Hospital of Lanzhou University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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;
9. 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.
Exclusion Criteria:
- 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;
- Participate in another clinical trial of lymphoma treatment at the same time;
- Unsuitable for enrollment by the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: experimental group
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.
|
Zanubrutinib, 180mg, bid, p.o., d1-28; Treatment cycles every 28 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free survival (EFS)
Time Frame: up to 36 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Conversion rate of partial response (PR) to CR
Time Frame: up to 36 months
|
the total proportion of patients who had a partial response to initial therapy converted to CR at any time point after starting zanubrutinib maintenance therapy and will be reported as converted to CR at 3, 6, 12 months, and any other time point.
|
up to 36 months
|
Progression-free survival (PFS)
Time Frame: up to 36 months
|
PFS was defined as the duration from initiation of zanubrutinib maintenance therapy to disease progression, CR recurrence, or death, whichever occurred first.
|
up to 36 months
|
Overall survival (OS)
Time Frame: up to 36 months
|
OS was defined as the duration from the date of initiation of zanubrutinib maintenance therapy to the date of death.
|
up to 36 months
|
adverse event
Time Frame: 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
|
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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. Erratum In: Mol Cancer. 2019 Apr 3;18(1):79.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Zanubrutinib
Other Study ID Numbers
- ZEBUBU22
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
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.
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.
Clinical Trials on Diffuse Large B-cell Lymphoma (DLBCL)
-
Memorial Sloan Kettering Cancer CenterSanofi; Columbia University; Medical College of Wisconsin; University of Rochester and other collaboratorsActive, not recruitingDiffuse Large B-cell Lymphoma (DLBCL) | Relapsed Diffuse Large B-cell Lymphoma (DLBCL) | Refractory Diffuse Large B-cell Lymphoma (DLBCL)United States
-
University Health Network, TorontoNot yet recruitingDiffuse Large B Cell Lymphoma (DLBCL)Canada
-
Hoffmann-La RocheRecruitingDiffuse Large B-Cell Lymphoma (DLBCL)United States
-
AmgenMerck Sharp & Dohme LLCCompletedRelapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)United States, Germany, Spain, Australia, Netherlands, France
-
Fondazione Italiana Linfomi ONLUSCompletedDiffuse Large B Cell Lymphoma (DLBCL) | Elderly Patients (>65 Years)Italy
-
2seventy bioRecruitingDiffuse Large B Cell Lymphoma (DLBCL)United States
-
Arbeitsgemeinschaft medikamentoese TumortherapieHoffmann-La RocheCompletedDiffuse Large B-Cell Lymphoma (DLBCL) | Follicular NHL Grade 3bHong Kong, Thailand, Sweden, Taiwan, Mexico, Austria, Serbia, China, Czech Republic, Australia, Malaysia, Croatia, Israel, South Africa, Bosnia and Herzegovina, Brazil, Bulgaria, Estonia, Latvia, Macedonia, The Former Yugoslav... and more
-
Fondazione Italiana Linfomi - ETSNot yet recruitingClassical Hodgkin Lymphoma | Primary Mediastinal Large B-cell Lymphoma (PMBCL) | Diffuse Large B Cell Lymphoma (DLBCL)Italy
-
Memorial Sloan Kettering Cancer CenterActinium PharmaceuticalsRecruitingDiffuse Large B-cell Lymphoma | B-ALL | DLBCL | DLBCL, Nos Genetic Subtypes | B ALL | Dlbcl-Ci | DLBCL Unclassifiable | DLBCL Activated B-Cell Type | DLBCL Germinal Center B-Cell Type | HGBL | HGBL, NosUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
Clinical Trials on Zanubrutinib
-
Zhang Lei, MDRecruitingThrombocytopenia | Antiphospholipid Syndrome | TreatmentChina
-
Fudan UniversityRecruiting
-
Xuanwu Hospital, BeijingRecruitingNeuromyelitis OpticaChina
-
Zhang LeiRecruitingImmune Thrombocytopenia | TreatmentChina
-
Matthew C. BakerStanford UniversityRecruiting
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNot yet recruitingLymphomaNorway, Netherlands, Denmark, Belgium
-
The First Affiliated Hospital of Soochow UniversityRecruitingUntreated Mantle Cell LymphomaChina
-
Fudan UniversityRecruitingDiffuse Large B-cell Lymphoma(DLBCL)China
-
Fudan UniversityRecruitingMantle Cell Lymphoma | Maintenance TherapyChina
-
Huazhong University of Science and TechnologyRecruitingDiffuse Large B Cell LymphomaChina