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Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM (ZBR)

Primary Purpose

Waldenstrom Macroglobulinemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib, Bendamustine and Rituximab
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenstrom Macroglobulinemia focused on measuring Waldenstrom macroglobulinemia, Zanubrutinib, newly diagnosed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP No treatment regimen containing fludarabine Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids) The above treatment did not reach the treatment response (MR) 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): Symptomatic hyperviscosity; Symptomatic peripheral neuropathy; Amyloidosis; Cold agglutinin disease; cryoglobulinemia; Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L); Giant lymph nodes; 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; 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 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.

Sites / Locations

  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zanubrutinib, bendamustine, rituximab combination therapy Group

Arm Description

Patients were treated with ZBR regimen for 6 cycles, followed by zanubrutinib monotherapy for an additional 6 months.

Outcomes

Primary Outcome Measures

Best combined complete response (CR) and very good partial response (VGPR)
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).

Secondary Outcome Measures

Overall objective response rate (ORR), complete response rate(CR),major response rate(MR)
using criteria from 6th international workshop on WM
Time to response, time to best response
Defined as after initiation of treatment, the time interval between the first documented remission of disease
Overall survival(OS)
3-year OS rate after treatment
Progression free survival(PFS)
3-year PFS rate after treatment
Duration of Response
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.
Time to Next 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
Safety of treatment regimens
Defined as treatment-related toxicity

Full Information

First Posted
June 13, 2023
Last Updated
June 13, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05914662
Brief Title
Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM
Acronym
ZBR
Official Title
Phase II Clinical Study of Zanubrutinib Combined With Bendamustine and Rituximab (ZBR) for Time-limited Treatment of Waldenstrom Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2023 (Actual)
Primary Completion Date
March 15, 2025 (Anticipated)
Study Completion Date
December 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom Macroglobulinemia
Keywords
Waldenstrom macroglobulinemia, Zanubrutinib, newly diagnosed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Patients were treated with ZBR regimen for 6 cycles, followed by Zanubrutinib monotherapy for 6 months.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zanubrutinib, bendamustine, rituximab combination therapy Group
Arm Type
Experimental
Arm Description
Patients were treated with ZBR regimen for 6 cycles, followed by zanubrutinib monotherapy for an additional 6 months.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib, Bendamustine and Rituximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Best combined complete response (CR) and very good partial response (VGPR)
Description
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).
Time Frame
up to the end of 12 cycles of treatment(each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Overall objective response rate (ORR), complete response rate(CR),major response rate(MR)
Description
using criteria from 6th international workshop on WM
Time Frame
up to the end of 12 cycles of treatment(each cycle is 28 days)
Title
Time to response, time to best response
Description
Defined as after initiation of treatment, the time interval between the first documented remission of disease
Time Frame
up to the end of 12 cycles of treatment(each cycle is 28 days)
Title
Overall survival(OS)
Description
3-year OS rate after treatment
Time Frame
Up to 3 years after the end of treatment
Title
Progression free survival(PFS)
Description
3-year PFS rate after treatment
Time Frame
Up to 3 years after the end of treatment
Title
Duration of Response
Description
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.
Time Frame
Up to 3 years after the end of treatment
Title
Time to Next Treatment
Description
Defined as the amount of time from the start of trial until the patient requires a new form of treatment to treat their WM
Time Frame
Up to 3 years after the end of treatment
Title
Safety of treatment regimens
Description
Defined as treatment-related toxicity
Time Frame
Up to 3 years after the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP No treatment regimen containing fludarabine Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids) The above treatment did not reach the treatment response (MR) 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): Symptomatic hyperviscosity; Symptomatic peripheral neuropathy; Amyloidosis; Cold agglutinin disease; cryoglobulinemia; Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L); Giant lymph nodes; 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; 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shuhua Yi, Dr.
Phone
86-22-23909106
Email
yishuhua@ihcams.ac.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Lugui Qiu, Dr.
Phone
86-22-23909172
Email
qiulg@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shuhua Yi, Dr.
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shuhua Yi, Dr.
Phone
86-22-23909106
Email
yishuhua@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Lugui Qiu, Dr.
Phone
86-22-23909172
Email
qiulg@ihcams.ac.cn

12. IPD Sharing Statement

Plan to Share IPD
No
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Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM

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