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

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04835870

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Non-GCB/ABC Diffuse Large B-Cell Lymphoma	Drug: Zanubrutinib Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Zanubrutinib Combination With R-CHOP in Treating Patients With Newly Diagnosed Untreated Non-GCB DLBCL

Actual Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-CHOP + Zanubrutinib Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)	Drug: Zanubrutinib Zanubrutinib-160mg bid PO d0-d20(1-21d) Other Names: BTK inhibitors Drug: Rituximab Rituximab-375 mg/m2 i.v d0 (/21d) Other Names: MabThera Drug: Cyclophosphamide Cyclophosphamide-750 mg/m2 i.v d1 (/21d) Other Names: CTX Drug: Doxorubicin Doxorubicin-50 mg/m2 i.v d1 (/21d) Other Names: ADM Drug: Vincristine Vincristine-1.4 mg/m2 i.v d1 (/21d)(2 mg max) Other Names: VCR Drug: Prednisone Prednisone-100 mg p.o d1-d5 (/21d) Other Names: Prednisonum

Arm

Intervention/Treatment

Experimental: R-CHOP + Zanubrutinib

Zanubrutinib plus Rituximab, Cyclosphosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP)

Drug: Zanubrutinib

Zanubrutinib-160mg bid PO d0-d20(1-21d)

Other Names:

BTK inhibitors

Drug: Rituximab

Rituximab-375 mg/m2 i.v d0 (/21d)

Other Names:

MabThera

Drug: Cyclophosphamide

Cyclophosphamide-750 mg/m2 i.v d1 (/21d)

Other Names:

CTX

Drug: Doxorubicin

Doxorubicin-50 mg/m2 i.v d1 (/21d)

Other Names:

ADM

Drug: Vincristine

Vincristine-1.4 mg/m2 i.v d1 (/21d)(2 mg max)

Other Names:

VCR

Drug: Prednisone

Prednisone-100 mg p.o d1-d5 (/21d)

Other Names:

Prednisonum

Outcome Measures

Primary Outcome Measures

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

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
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.
Overall Survival [up to 18 months]
OS will be assessed from the first ZR-CHOP given to 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed Non-GCB DLBCL with extrinsic involvement
Age ≥ 18 years
Measurable disease of at least 15mm(node)/10mm（extranodal）
ECOG performance status 0-2
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
Adequate bone marrow function:Platelet count (≥ 50×10^{9/L);Hemoglobin (≥ 8 g/dL);The
absolute value of neutrophils (≥1.0×10}9/L)
Estimated survival time ≥3 months
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:

Accepted major surgery within 4 weeks before treatment;
Diagnosis of primary mediastinal lymphoma or primary CNS lymphoma;
Previous history of indolent lymphoma;
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;
History of intracranial haemorrhage in preceding 6 months,requires or receiving anticoagulation with warfarin or equivalent antagonists;
Requires treatment with a strong/medium CYP3A inducer;
The previous use of anthracycline-based drugs > 150 mg/m2;
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;
HIV infection and/or active hepatitis B or active hepatitis C;
Uncontrolled systemic infection;
Pregnant or breasting-feeding women;
According to the researchers' judgment, patients' underlying condition may increase their risk of receiving research drug treatment, or confuse their judgment on toxic reactions.