Zanubrutinib Combined With Standard Chemotherapy in the Treatment for Patients With Diffuse Large B Cell Lymphoma

Henan Cancer Hospital

Status and phase: Suspended; Phase 2

Conditions: CD79B Gene Mutation; CD79A Gene Mutation; Diffuse Large B Cell Lymphoma

Treatments: Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Prednisone; Drug: Zanubrutinib; Drug: Vincristine

Study type: Interventional

Funder types: Other

Identifiers

NCT04668365

HNSZLYYNHL05

Details and patient eligibility

About

This is a prospective single arm, multi-center, phase II clinical trial to observe the efficacy and safety of zanubrutinib combined with standard chemotherapy in the treatment for patients with diffuse large B cell lymphoma and CD79A/CD79B genetic abnormality.

Full description

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL). Currently, R-CHOP is world-widely used in the first-line treatment for DLBCL. There are about one second of patients suffering relapse and drug resistance. ABC-DLBCL mainly relies on the chronical activity of BCR signal, which can activate the downstream NF-kB pathway through BTK and MYD88, thereby promoting the occurrence of tumors. A study by Wyndham H Wilson et al. showed that 23% of ABC-DLBCL patients were accompanied by acquired functional mutations of the BCR component CD79A/CD79B. Zanubrutinib is a new BTK inhibitor. The goal of our trial is to assess the efficacy and safety of zanubrutinib combined with standard chemotherapy in the treatment for patients with diffuse large B cell lymphoma and CD79A/CD79B genetic abnormality.

Enrollment: 59 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age between 18 to 75 years old (including 18 and 75)
2. Diagnosed as diffuse large B cell lymphoma
3. CD79A/CD79B genetic abnormality
4. Subjects with untreated or relapsed/refractory DLBCL
5. Having at least one measurable lesions
6. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1
7. Life expectancy no less than 3 months
8. enough main organ function
9. Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study
10. Agreeing to sign the written informed consents

Exclusion criteria

1. Diagnosed as high-grade B-cell lymphoma, including non-specified and double-strike or triple-strike
2. Diagnosed as grey-zone lymphoma
3. Diagnosed as primary mediastinal large B-cell lymphoma
4. Diagnosed as CD20 negative diffuse large B-cell lymphoma
5. Active malignant tumor need be treated at the same time
6. Other malignant tumor history
7. Serious surgery and trauma less than two weeks
8. Systemic therapy for serious acute/chronic infection
9. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months
10. Vaccination with live attenuated vaccine less than 4 weeks
11. HIV-positive, AIDS patients and untreated active hepatitis
12. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months
13. Patients with a history of mental illness
14. Researchers determine unsuited to participate in this trial

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 1 patient group

Zanubrutinib Combined With Standard Chemotherapy

Experimental group

Description:

A: For the first-line treatment: Rituximab, 375mg/m2, Intravenous administration on day 0, combined with regimen：CHOP (Cyclophosphamide, Epirubicin, Vincristine and Prednisone): repeated every 3 weeks, up to 6 cycles. Zanubrutinib, 160mg twice daily continuous oral administration from 2 to 6 cycles for patients with CD79A/CD79B genetic abnormality. Zanubrutinib combined with Rituximab for the 7 cycle. B: For R/R DBCLC: Rituximab, 375mg/m2, Intravenous administration on day 0, combined with regimen: GemOx(Gemcitabine, Oxaliplatin)/ DHAP(Cisplatin, Cytarabine, Dexamethasone)/ ICE(Ifosfamide, Etoposide, Carboplatin)/ GDP(Gemcitabine, Cisplatin, Dexamethasone): repeated every 3 weeks, up to 5 cycles. Zanubrutinib, 160mg twice daily continuous oral administration from 2 to 5 cycles for patients with CD79A/CD79B genetic abnormality. Maintenance treatment: Zanubrutinib, 160mg twice daily continuous oral administration for 12 months.

Treatment:

Drug: Vincristine

Drug: Prednisone

Drug: Zanubrutinib

Drug: Rituximab

Drug: Cyclophosphamide

Drug: Epirubicin