Zanubrutinib Plus R-CHOP for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Phase 2

Recruiting

• Conditions: Non-GCB/ABC Diffuse Large B-Cell Lymphoma
• Interventions: Drug: Zanubrutinib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

• Registration Number: NCT04835870
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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.

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2021-04-05
• Study First Submitted QC: 2021-04-05
• Study First Posted: 2021-04-08
• Status Verified: 2022-03
• Last Update Submitted: 2022-09-14
• Last Update Posted: 2022-09-16
• Primary Completion: 2025-10-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 78

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
R-CHOP + Zanubrutinib	Rituximab	Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
R-CHOP + Zanubrutinib	Vincristine	Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
R-CHOP + Zanubrutinib	Zanubrutinib	Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
R-CHOP + Zanubrutinib	Cyclophosphamide	Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
R-CHOP + Zanubrutinib	Doxorubicin	Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)
R-CHOP + Zanubrutinib	Prednisone	Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)

Primary Outcome Measures

Name	Time	Method
Progression-free Survival(PFS)	up to 18 months	To measure the duration of response to ZR-CHOP over a follow-up period of 18 months

Secondary Outcome Measures

Name	Time	Method
Complete Response Rate	up to 18 months	Number of patients who achieved complete response after treatment by ZR-CHOP
Duration of Response	up to 18 months	Duration of overall response will be assessed from the first ZR-CHOP given to progression,death or last follow-up.
Adverse events profile	Measured from start of treatment until 28 days after last dose	Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated
Overall Response Rate (ORR)	up to 18 months	To measure the duration of response to ZR-CHOP over a follow-up period of 18 months
Overall Survival	up to 18 months	OS will be assessed from the first ZR-CHOP given to death or last follow-up.

Trial Locations

Locations (16)

The First Affiliated Hospital of USTC Anhui Provincial Hospital; 🇨🇳 Hefei, Anhui, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

The First Affiliated Hospital of Xiamen University; 🇨🇳 Xiamen, Fujian, China

The First People's Hospital of Changzhou; 🇨🇳 Changzhou, Jiangsu, China

Jiangsu Cancer Hospital; 🇨🇳 Nanjing, Jiangsu, China

Nanjing Drum Tower Hospital; 🇨🇳 Nanjing, Jiangsu, China

Zhongda Hospital Southeast University; 🇨🇳 Nanjing, Jiangsu, China

Nantong Tumor Hospital; 🇨🇳 Nantong, Jiangsu, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Changshu No.1 People's Hospital; 🇨🇳 Suzhou, Jiangsu, China

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