Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM (ZBR)

June 13, 2023 updated by: Institute of Hematology & Blood Diseases Hospital

Phase II Clinical Study of Zanubrutinib Combined With Bendamustine and Rituximab (ZBR) for Time-limited Treatment of Waldenstrom Macroglobulinemia

This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom macroglobulinemia, The combination therapy is expected to improve the remission depth, prolong the remission time, and improve the progression-free survival and overall survival of newly diagnosed WM patients. On the one hand, the patients have to bear a long-term economic burden, which is often difficult for some patients to adhere to for a long time. On the other hand, in the course of long-term treatment of BTKi, drug resistance and intolerable side effects are prone to occur. At the same time, it can prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased withdrawal of WM

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

WM not only has the characteristics of lymphoma, such as lymphadenopathy, hepatosplenomegaly, and tumor cells expressing CD20, but also has the characteristics of myeloma, such as secreting monoclonal IgM, and tumor cells expressing plasma cell differentiation marker CD38, etc. Clinical studies have also shown that BR regimen and BTK inhibitor zanubrutinib are effective for WM.

This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom macroglobulinemia, The combination therapy is expected to improve the remission depth, prolong the remission time, and improve the progression-free survival and overall survival of newly diagnosed WM patients. On the one hand, the patients have to bear a long-term economic burden, which is often difficult for some patients to adhere to for a long time. On the other hand, in the course of long-term treatment of BTKi, drug resistance and intolerable side effects are prone to occur. At the same time, it can prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased withdrawal of WM. This prospective phase II study was designed to evaluate the rate of deep response in newly diagnosed symptomatic WM. Eligible patients received ZBR for 6 cycles followed by zanubrutinib monotherapy for an additional 6 months.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

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

Study Contact Backup

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Institute of Hematology & Blood Diseases Hospital
        • Contact:
        • 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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • The gender of the patient is not limited, and the age is ≥18 years old;
  • Must meet WM's diagnostic standards;
  • The patient is an untreated or patient who has not undergone standard treatment.

  • The specific conditions are as follows:

    1. No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP
    2. No treatment regimen containing fludarabine
    3. Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids)
    4. The above treatment did not reach the treatment response (MR)
    5. If the above treatment has been applied, the treatment needs to be stopped for 2 weeks before entering the group to start treatment

  • The indications for the treatment of indolent lymphoma mainly include (at least one of the following conditions):

    1. Symptomatic hyperviscosity;
    2. Symptomatic peripheral neuropathy;
    3. Amyloidosis;
    4. Cold agglutinin disease; cryoglobulinemia;
    5. Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L);
    6. Giant lymph nodes;
    7. Those with systemic systemic symptoms: for two weeks/recurrent fever (above 38℃) and not caused by infection, or Night sweats and/or weight loss >10% within 6 months;
    8. The disease progresses rapidly, for example, the lymph nodes increase by more than 50% within 2 months, and/or peripheral blood lymphocytes absolute value doubling time <6 months, and/or rapid hemoglobin or platelet non-autoimmune causes slow down
    9. When there is evidence that the disease has transformed.
  • ECOG score ≤ 2 points
  • Laboratory examination: neutrophils ≥ 0.75×10^9/L; platelets ≥ 50×10^9/L; total bilirubin ≤ 2.5 times upper limit; alanine aminotransferase/aspartate aminotransferase ≤3 times upper limit. Creatinine clearance rate ≥ 30ml/min.
  • The patient's expected survival time is ≥ 3 months.

Exclusion Criteria:

  • Malignant tumors (including active central nervous system lymphoma) other than B-NHL have been diagnosed or treated within the past year;
  • There is clinical evidence that large cell lymphoma transformation has occurred;
  • Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)> 3 times the upper limit of normal value, aspartate aminotransferase (AST)> 3 times the upper limit of normal value, total bilirubin (TBIL)> upper limit of normal value 2 Times, serum creatinine clearance rate <30ml/min;
  • Other serious medical conditions will affect the study (such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). The decision-making power belongs to the researcher;
  • Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
  • Central nervous system dysfunction with clinical manifestations or central invasion (Bing-Neel syndrome);
  • Patients who have undergone major surgery (not including lymph node biopsy) within the past 14 days or expected major surgery during treatment;
  • Inability to swallow capsules or suffer from malabsorption syndrome, diseases that significantly affect gastrointestinal function, have undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, partial or complete intestinal obstruction.
  • Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.
  • Women who are pregnant or breastfeeding, women of childbearing age who have not taken contraception;
  • Allergy to the drugs used.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zanubrutinib, bendamustine, rituximab combination therapy Group
Patients were treated with ZBR regimen for 6 cycles, followed by zanubrutinib monotherapy for an additional 6 months.
Drug: Zanubrutinib, Bendamustine and Rituximab
Zanubrutinib, 160mg orally, twice a day; Bendamustine 70 mg/m2 on days 1 and 2 of each cycle; Rituximab (375 mg/m2 intravenously on day 0 of each cycle. ZBR was administered every 4 weeks for a total of 6 cycles, followed by maintenance therapy with zanubrutinib monotherapy for another 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best combined complete response (CR) and very good partial response (VGPR)
Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
To evaluate the efficacy of zanubrutinib plus bendamustine and rituximab (ZBR) regimen in the treatment of newly diagnosed WM patients, mainly the best deep response rate, namely the best deep response rate (VGPR and above).
up to the end of 12 cycles of treatment(each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall objective response rate (ORR), complete response rate(CR),major response rate(MR)
Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
using criteria from 6th international workshop on WM
up to the end of 12 cycles of treatment(each cycle is 28 days)
Time to response, time to best response
Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
Defined as after initiation of treatment， the time interval between the first documented remission of disease
up to the end of 12 cycles of treatment(each cycle is 28 days)
Overall survival(OS)
Time Frame: Up to 3 years after the end of treatment
3-year OS rate after treatment
Up to 3 years after the end of treatment
Progression free survival(PFS)
Time Frame: Up to 3 years after the end of treatment
3-year PFS rate after treatment
Up to 3 years after the end of treatment
Duration of Response
Time Frame: Up to 3 years after the end of treatment
DOR is defined as the time from the first occurrence of overall response (CR, PR or MR) until disease progression or death due to any cause.
Up to 3 years after the end of treatment
Time to Next Treatment
Time Frame: Up to 3 years after the end of treatment
Defined as the amount of time from the start of trial until the patient requires a new form of treatment to treat their WM
Up to 3 years after the end of treatment
Safety of treatment regimens
Time Frame: Up to 3 years after the end of treatment
Defined as treatment-related toxicity
Up to 3 years after the end of treatment

Collaborators and Investigators

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

Sponsor

Institute of Hematology & Blood Diseases Hospital

Investigators

  • Principal Investigator: Shuhua Yi, Dr., Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

February 15, 2023

Primary Completion (Estimated)

March 15, 2025

Study Completion (Estimated)

December 15, 2025

Study Registration Dates

First Submitted

June 13, 2023

First Submitted That Met QC Criteria

June 13, 2023

First Posted (Actual)

June 22, 2023

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BDH-WM2020/05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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