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

December 7, 2021 updated by: Wang Xin, Shandong Provincial Hospital

A Multi-center, Prospective Clinical Study of Zanubrutinib, Rituximab and Combination Chemotherapy in Patients With Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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. B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. 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.

High-grade B-cell lymphoma (HGBL)-DH/TH with MYC/BCL2 and/or BCL6 translocation, accounts for about 7-10% in DLBCL. The remission rate of conventional chemotherapy is low.(ORR:32%,CR:12%). The median OS is 12 months. The survival outcome of induction chemotherapy is improved limited compared to R-CHOP. Currently, there are a lack of effective treatments options for HGBL. How to improve curative effect needs more research.

Zanubrutinib is an oral small molecule BTK inhibitor, and has shown good efficacy and safety in multiple subtypes of B-cell lymphoma. Zanubrutinib received FDA approval for adult mantle-cell lymphoma (MCL) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) patients who have received at least one previous treatment on 15 Nov 2019, becoming the first US-listed Chinese innovative anti-cancer drug. However, the efficacy of zanubrutinib in highly aggressive B-cell lymphoma remains to be further studied.

Therefore, we present this study protocol to add Zanubrutinib to the first-line treatment of highly aggressive B-NHL, applying zanubrutinib combined with rituximab plus chemotherapy in the treatment of highly aggressive B-NHL compared to rituximab plus chemotherapy.

Study Type

Interventional

Enrollment (Anticipated)

160

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xin Wang, PhD
  • Phone Number: 86-531-13156012606
  • Email: xinw@sdu.edu.cn

Study Contact Backup

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China, 250021
        • Recruiting
        • Department of Hematology, Shandong Provincial Hospital
        • Contact:
          • Xin Wang, MD, PHD
          • Phone Number: +86-531-13156012606
          • Email: xinw@sdu.edu.cn
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥18 years, gender not limited
  2. Newly and histologically diagnosed aggressive B-NHL
  3. Patients who have not received systematic chemotherapy or immunotherapy;
  4. Patients with at least ≥1 tumor foci with a measurable maximum axis exceeding 1.5 cm;
  5. Eastern cancer collaboration group(ECOG) physical status score: 0-2
  6. 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;
  7. expected survival time ≥3 months;
  8. Willing to take contraceptive measures during the trial period and within 1 week after the trial ends;
  9. Voluntarily sign written informed consent before screening.

Exclusion Criteria:

  1. Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years;
  2. Patients scheduled for major surgery(except for examination for diagnostic purposes) within 4 weeks or participating in drug/device clinical trials;
  3. Prior or concurrent indolent B-cell lymphoma transformation;
  4. Uncontrolled or significant cardiovascular disease;
  5. 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;
  6. Stroke or intracranial hemorrhage within 6 months;
  7. Subjects with clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.)
  8. Active or uncontrolled HBV (HBsAg positive and HBV DNA titer positive), HCV Ab positive or HIV positive;
  9. 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)
  10. Allergies or hypersensitivity reactions to zanubrutinib, rituximab or any other component of the applicable study drug;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zanubrutinib+R+chemotherapy
Zanubrutinib+R-CHOP; Zanubrutinib+R-DA-EPOCH; Zanubrutinib+R-HD MTX
Drug: Zanubrutinib+R-CHOP; Zanubrutinib+R-DA-EPOCH; Zanubrutinib+R-HD MTX

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.
Active Comparator: R+chemotherapy
R-CHOP; R-DA-EPOCH; R-HD MTX
Drug: R-CHOP; R-DA-EPOCH; R-HD MTX

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: 3 years
per 3 and 6 cycle
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 3 years
3 years
Occurrence of adverse events and serious adverse events
Time Frame: 3 years
per 3 and 6 cycle
3 years
Overall Survival (OS)
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shandong Provincial Hospital

Investigators

  • Principal Investigator: Xin Wang, PhD, Shandong Provincial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2021

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

December 7, 2021

First Submitted That Met QC Criteria

December 7, 2021

First Posted (Actual)

December 21, 2021

Study Record Updates

Last Update Posted (Actual)

December 21, 2021

Last Update Submitted That Met QC Criteria

December 7, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B-NHL002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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