Non-GCB/ABC Diffuse Large B-Cell Lymphoma
Conditions
Keywords
Zanubrutinib, R-CHOP, Newly diagnosed Non-GCB DLBCL
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.
Interventions
DRUGZanubrutinib
Zanubrutinib-160mg bid PO d0-d20(1-21d)
DRUGRituximab
Rituximab-375 mg/m2 i.v d0 (/21d)
DRUGCyclophosphamide
Cyclophosphamide-750 mg/m2 i.v d1 (/21d)
DRUGDoxorubicin
Doxorubicin-50 mg/m2 i.v d1 (/21d)
DRUGVincristine
Vincristine-1.4 mg/m2 i.v d1 (/21d)(2 mg max)
DRUGPrednisone
Prednisone-100 mg p.o d1-d5 (/21d)
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Contacts
Primary ContactCaixia Li, M.D
Backup ContactJia Chen, M.D
Outcome results
None listed