Study of Zanubrutinib, Rituximab and Combination Chemotherapy in Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma

NCT05164770 | Unknown Phase 3

• 1 other identifier: B-NHL002
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Non-Hodgkin lymphoma (NHL), with high aggressiveness and mortality, is one of the top ten high-incidence tumors in the world and is among the ten most prevalent cancers worldwide with the fastest growing incidence. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. Zanubrutinib is an oral small molecule BTK inhibitor, and has shown good efficacy and safety in multiple subtypes of B-cell lymphoma. However, the efficacy of zanubrutinib in highly aggressive B-cell lymphoma remains to be further studied

Conditions

High Grade B-Cell Lymphoma, Not Otherwise Specified; High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements; Diffuse Large B Cell Lymphoma; B-cell Non Hodgkin Lymphoma; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• ORR

  per 3 and 6 cycle

  3 years

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  3 years

• Occurrence of adverse events and serious adverse events

  3 years

• Overall Survival (OS)

  3 years

Study Arms (2)

Zanubrutinib+R+chemotherapy

EXPERIMENTAL

Zanubrutinib+R-CHOP; Zanubrutinib+R-DA-EPOCH; Zanubrutinib+R-HD MTX

Drug: Zanubrutinib+R-CHOP; Zanubrutinib+R-DA-EPOCH; Zanubrutinib+R-HD MTX

R+chemotherapy

ACTIVE COMPARATOR

R-CHOP; R-DA-EPOCH; R-HD MTX

Drug: R-CHOP; R-DA-EPOCH; R-HD MTX

Interventions

Zanubrutinib+R-CHOP; Zanubrutinib+R-DA-EPOCH; Zanubrutinib+R-HD MTX DRUG

Zanubrutinib+R-CHOP Regimen: Zanubrutinib 160mg bid; R-CHOP: Rituximab 375mg/m2 d0, Cyclophosphamide 750mg /m2 d1, Doxorubicin 50mg /m2 or Doxorubicin liposome 30-40 mg /m2 d1, Vincristine 1.4mg /m2 or Vindesine 3mg /m2 d1, Prednisone 100mg d1-5. Every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance to chemotherapy. Zanubrutinib+R-DA-EPOCH Regimen: Zanubrutinib 160mg bid; R-DA-EPOCH: Rituximab 375mg/m2 d0, Etoposide 50mg/ m2, Epirubicin 15mg/ m2, Vincristine 0.4mg/ m2, d1-4, Cyclophosphamide (CTX) 750mg/ m2 d5, Prednisone 60mg/ m2 d1-5. Every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance to chemotherapy. Zanubrutinib+R-HD MTX Regimen: Zanubrutinib 160mg bid; R-HD MTX: Rituximab 375mg/m2 d0, Methotrexate 3.5g/m2 d1. Every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance to chemotherapy.

Zanubrutinib+R+chemotherapy

R-CHOP; R-DA-EPOCH; R-HD MTX DRUG

R-CHOP: Rituximab 375mg/m2 d0, Cyclophosphamide 750mg/m2 d1, Doxorubicin 50mg/m2 or Doxorubicin liposome 30-40 mg /m2 d1, Vincristine 1.4mg/m2 or Vindesine 3mg/m2 d1, Prednisone 100mg d1-5. Every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance to chemotherapy. R-DA-EPOCH: Rituximab 375mg/m2 d0, Etoposide 50mg/m2, Epirubicin 15mg/m2, Vincristine 0.4mg/ m2, d1-4, Cyclophosphamide (CTX) 750mg/ m2 d5, Prednisone 60mg/ m2 d1-5. Every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance to chemotherapy. R-HD MTX: Rituximab 375mg/m2 d0, Methotrexate 3.5g/m2 d1. Every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance to chemotherapy.

R+chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, gender not limited
• Newly and histologically diagnosed aggressive B-NHL
• Patients who have not received systematic chemotherapy or immunotherapy;
• Patients with at least ≥1 tumor foci with a measurable maximum axis exceeding 1.5 cm;
• Eastern cancer collaboration group(ECOG) physical status score: 0-2
• a)Blood routine: (independent of growth factor support or transfusion within 7 days of study entry) neutrophils absolute value ≥1.5×109/L, platelets ≥75×109/L, b) Coagulation function: INR ≤2.5 times ULN, c) Blood biochemistry: total bilirubin ≤2 times ULN, AST or ALT≤2.5 times ULN d) Ccr ≥ 30 mL/min;
• expected survival time ≥3 months;
• Willing to take contraceptive measures during the trial period and within 1 week after the trial ends;
• Voluntarily sign written informed consent before screening.

You may not qualify if:

• Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years;
• Patients scheduled for major surgery(except for examination for diagnostic purposes) within 4 weeks or participating in drug/device clinical trials;
• Prior or concurrent indolent B-cell lymphoma transformation;
• Uncontrolled or significant cardiovascular disease;
• Had active bleeding within 2 months prior to screening, or was taking anticoagulant drugs, or was considered by the investigator to have a clear tendency to bleeding;
• Stroke or intracranial hemorrhage within 6 months;
• Subjects with clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.)
• Active or uncontrolled HBV (HBsAg positive and HBV DNA titer positive), HCV Ab positive or HIV positive;
• Uncontrolled, active systemic fungal, bacterial, viral, or other infections (defined as showing persistent signs/symptoms related to infection, despite the use of appropriate antibiotics or other treatments without improvement)
• Allergies or hypersensitivity reactions to zanubrutinib, rituximab or any other component of the applicable study drug;

Sponsors & Collaborators

• Shandong Provincial Hospital: lead

Study Sites (1)

Department of Hematology, Shandong Provincial Hospital

Jinan, Shandong, 250021, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xin Wang, PhD

  Shandong Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xin Wang, PhD

CONTACT

86-531-13156012606; xinw@sdu.edu.cn

Xiangxiang Zhou, PhD

CONTACT

86-531-15866695595; xiangxiangzhou@sdu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Hematology

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: December 21, 2021
• Study Start: March 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: December 21, 2021

Record last verified: 2021-12

Locations

CN (1)