Clinical trial NCT04835870: Zanubrutinib Plus R-CHOP for Patients With Newly Diagnosed Untreated Non-GCB DLBCL
Official title: Zanubrutinib Combination With R-CHOP in Treating Patients With Newly Diagnosed Untreated Non-GCB DLBCL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-GCB/ABC Diffuse Large B-Cell Lymphoma
Keywords: Zanubrutinib, R-CHOP, Newly diagnosed Non-GCB DLBCL
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2021-04-08
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Aim of this study will evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP for newly diagnosed untreated Non-GCB DLBCL Patients

Detailed description: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. According to Hans' algorithms, DLBCL can be identified as 2 subtypes: germinal b-cell-like(GCB) and non-germinal b-cell-like(non-GCB). Approximately 50 to 60% of DLBCL was non-GCB subtype DLBCL.The non-GCB DLBCL revealed poor clinical outcomes. Bruton's tyrosine kinase (BTK) inhibitors have established therapeutic activity in B cell malignancies, with potential activity in non-GCB DLBCL. This study will evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP for newly diagnosed untreated Non-GCB DLBCL Patients.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed Non-GCB DLBCL with extrinsic involvement
2. Age ≥ 18 years
3. Measurable disease of at least 15mm(node)/10mm（extranodal）
4. ECOG performance status 0-2
5. Adequate organ function:Cardiac ejection fraction (EF) ≥ 50%;Creatinine clearance rate (≥30 mL/min) of serum creatinine; Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) ≤3 times ULN
6. Adequate bone marrow function:Platelet count (≥ 50×10\^9/L);Hemoglobin (≥ 8 g/dL);The absolute value of neutrophils (≥1.0×10\^9/L)
7. Estimated survival time ≥3 months
8. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study

Exclusion Criteria:

1. Accepted major surgery within 4 weeks before treatment;
2. Diagnosis of primary mediastinal lymphoma or primary CNS lymphoma;
3. Previous history of indolent lymphoma;
4. Prior malignancy (other than DLBCL), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer 、malignant tonsilloma or carcinoma in situ;
5. History of intracranial haemorrhage in preceding 6 months,requires or receiving anticoagulation with warfarin or equivalent antagonists;
6. Requires treatment with a strong/medium CYP3A inducer;
7. The previous use of anthracycline-based drugs \> 150 mg/m2;
8. Evidence of complications or medical conditions, including but not limited, that may interfere the conduct of the study or place the patient at serious risk:significant cardiovascular disease(class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification、myocardial infarction within 6 months of screening、uncontrolled or symptomatic arrhythmias) and/or significant lung disease;
9. HIV infection and/or active hepatitis B or active hepatitis C;
10. Uncontrolled systemic infection;
11. Pregnant or breasting-feeding women;
12. According to the researchers' judgment, patients' underlying condition may increase their risk of receiving research drug treatment, or confuse their judgment on toxic reactions.

Primary outcomes:
measure: Progression-free Survival(PFS)
timeFrame: up to 18 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: up to 18 months
measure: Complete Response Rate
timeFrame: up to 18 months
measure: Duration of Response
timeFrame: up to 18 months
measure: Overall Survival
timeFrame: up to 18 months
measure: Adverse events profile
timeFrame: Measured from start of treatment until 28 days after last dose
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC Anhui Provincial Hospital
state: Anhui
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Changzhou
country: China
facility: The First People's Hospital of Changzhou
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Suzhou
country: China
facility: Changshu No.1 People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Suzhou Hongci Hematology Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Zhangjiagang First Peoples Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital Of Jiangnan University
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Jinan
country: China
facility: Shandong Provincial Hospital Affiliated to Shandong First Medical University
state: Shandong
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, M.D
role: STUDY_CHAIR
References: