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A Phase 2 Clinical Trial to Evaluate Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia (CZ-WM01)

Primary Purpose

Waldenström's Macroglobulinemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib
Bendamustine
Rituximab
Sponsored by
Shanghai Changzheng Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenström's Macroglobulinemia focused on measuring Waldenström's macroglobulinemia, Zanubrutinib, BR regimen, newly-diagnosed

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled: Newly diagnosed patients with waldenström's macroglobulinemia meeting at least one criterion for treatment according to consensus panel criteria from the eleventh IWWM. ECOG score: 0-3 points, estimated survival time exceeding 3 months. Did not receive any treatment for Waldenström's macroglobulinemia before screening, except for glucocorticoid therapy for autoimmune hemolysis. No serious damage to main organs, and meet the following laboratory examination indicators: creatinine clearance rate≥40ml/min, total bilirubin≤1.5 times of the upper limit of normal range; AST and ALT≤2.5 times of the upper limit of normal range; Myocardial enzyme≤2 times of the upper limit of normal range; ECHO must demonstrate left ventricular ejection fraction (LVEF) within the normal range, and no ECG abnormality with clinical significance. Neutrophil count≥1.5×10^9/L without growth factor therapy within 7 days before screening; Platelet count≥50×10^9/L without growth factor support or transfusion within 7 days before screening; Hemoglobin≥60 g/L without erythropoietin (EPO) support or transfusion within within 7 days before screening. No history of paroxysmal atrial fibrillation or chronic persistent atrial fibrillation. Able to swallow and Oral administration. The subjects complete all screening and evaluations listed in all trial protocols. The subjects who signed the informed consent form for chemotherapy. Exclusion Criteria: Waldenström's macroglobulinemia with amyloidosis or POEM syndrome HIV positive, or patients with active hepatitis A, hepatitis B, and hepatitis C infection; Or the number of copies of hepatitis B virus>10^2. Accompanied by other serious unstable diseases, including heart failure, renal failure, liver failure, hemorrhagic diseases, uncontrollable diabetes, etc. In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required. Serious infectious diseases (uncured pulmonary tuberculosis, pulmonary aspergillosis, etc.). Other uncontrolled malignancies (excluding non Melanoma skin cancer, cervical cancer in situ, bladder cancer cancer and breast cancer with disease-free survival of more than 5 years). Individuals with epilepsy, dementia, and other mental disorders who require medication treatment and are unable to understand or follow the research protocol. Drug use, medical, psychological, or social conditions that may interfere with participants' participation in the study or evaluation of the results. Pregnant and lactating women. Patients who are accounted to be not appropriate for this trail by investigator.

Sites / Locations

  • Shanghai Changzheng HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

zanubrutinib combined with BR regimen

Arm Description

Drug: zanubrutinib,160 mg oral capsules twice daily for 12 months Drug: Bendamustine,70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles. Drug: Rituximab,375 mg/m2 intravenously on day 0 of each cycle for 6 cycles.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response
The best deep response rate
defined as complete response (CR) and very good partial response (VGPR)

Secondary Outcome Measures

Progression-free Survival (PFS)
PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.
Overall Survival (OS)
OS is measured from the date of the initial of treatment to the date of the subject's death.
minimal residual disease (MRD) rate
MRD will be assessed at two on treatment timepoints (before start of cycles 7, 12) and every 6 months thereafter. MRD will be measured through bone marrow samples using flow cytometrey.

Full Information

First Posted
July 30, 2023
Last Updated
September 12, 2023
Sponsor
Shanghai Changzheng Hospital
Collaborators
RenJi Hospital, Huashan Hospital, Shanghai 6th People's Hospital, Huadong Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05979948
Brief Title
A Phase 2 Clinical Trial to Evaluate Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia
Acronym
CZ-WM01
Official Title
A Prospective, Open-label, Multicenter Study of Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
April 1, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Changzheng Hospital
Collaborators
RenJi Hospital, Huashan Hospital, Shanghai 6th People's Hospital, Huadong Hospital

4. Oversight

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

5. Study Description

Brief Summary
This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy of zanubrutinib combined with BR (Bendamustine/Rituximab) regimen in Chinese participants with newly-diagnosed Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the 11th International Workshop on Waldenström's Macroglobulinemia (IWWM). The investigators propose this combination will improve the deep remission compared to single Zanubrutinib or BR regimen and can be a time-limited regimen which will reduce the life-time therapy and benefit the patients.
Detailed Description
The study comprised an initial screening phase (up to 7 days), a single-arm treatment phase, and a follow-up phase. Subjects with newly-diagnosed Waldenström's macroglobulinemia can participate if all eligibility criteria are met. The participants will receive bendamustine and rituximab for 6 28-day cycles. Bendamustine will be given intravenously at 70-90 mg/m2 on days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2 intravenously), Zanubrutinib will be given orally 160mg Bid per day, up to 12 months. The participants with WM will also have disease assessment with Lymph node ultrasound and abdominal ultrasound each cource, serum IgM, serum protein electrophoresis (SPE), immunofixation (IFA), and viscosity assessments will be measured serially. A bone marrow aspiration and biopsy flow cytometry examination will be done before treatment and at response assessment at cycle 6 and 12. Durability of response will also be assessed every 3 months after treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenström's Macroglobulinemia
Keywords
Waldenström's macroglobulinemia, Zanubrutinib, BR regimen, newly-diagnosed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
zanubrutinib combined with BR regimen
Arm Type
Experimental
Arm Description
Drug: zanubrutinib,160 mg oral capsules twice daily for 12 months Drug: Bendamustine,70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles. Drug: Rituximab,375 mg/m2 intravenously on day 0 of each cycle for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Intervention Description
Zanubrutinib, 160 mg oral capsules twice daily for 12 months
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Intervention Description
Bendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response
Time Frame
up to the end of 12 cycles of treatment(each cycle is 28 days)
Title
The best deep response rate
Description
defined as complete response (CR) and very good partial response (VGPR)
Time Frame
Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.
Time Frame
Up to 6 years post first dose
Title
Overall Survival (OS)
Description
OS is measured from the date of the initial of treatment to the date of the subject's death.
Time Frame
Up to 6 years post first dose
Title
minimal residual disease (MRD) rate
Description
MRD will be assessed at two on treatment timepoints (before start of cycles 7, 12) and every 6 months thereafter. MRD will be measured through bone marrow samples using flow cytometrey.
Time Frame
Up to 6 years post first dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must meet all of the following criteria to be enrolled: Newly diagnosed patients with waldenström's macroglobulinemia meeting at least one criterion for treatment according to consensus panel criteria from the eleventh IWWM. ECOG score: 0-3 points, estimated survival time exceeding 3 months. Did not receive any treatment for Waldenström's macroglobulinemia before screening, except for glucocorticoid therapy for autoimmune hemolysis. No serious damage to main organs, and meet the following laboratory examination indicators: creatinine clearance rate≥40ml/min, total bilirubin≤1.5 times of the upper limit of normal range; AST and ALT≤2.5 times of the upper limit of normal range; Myocardial enzyme≤2 times of the upper limit of normal range; ECHO must demonstrate left ventricular ejection fraction (LVEF) within the normal range, and no ECG abnormality with clinical significance. Neutrophil count≥1.5×10^9/L without growth factor therapy within 7 days before screening; Platelet count≥50×10^9/L without growth factor support or transfusion within 7 days before screening; Hemoglobin≥60 g/L without erythropoietin (EPO) support or transfusion within within 7 days before screening. No history of paroxysmal atrial fibrillation or chronic persistent atrial fibrillation. Able to swallow and Oral administration. The subjects complete all screening and evaluations listed in all trial protocols. The subjects who signed the informed consent form for chemotherapy. Exclusion Criteria: Waldenström's macroglobulinemia with amyloidosis or POEM syndrome HIV positive, or patients with active hepatitis A, hepatitis B, and hepatitis C infection; Or the number of copies of hepatitis B virus>10^2. Accompanied by other serious unstable diseases, including heart failure, renal failure, liver failure, hemorrhagic diseases, uncontrollable diabetes, etc. In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required. Serious infectious diseases (uncured pulmonary tuberculosis, pulmonary aspergillosis, etc.). Other uncontrolled malignancies (excluding non Melanoma skin cancer, cervical cancer in situ, bladder cancer cancer and breast cancer with disease-free survival of more than 5 years). Individuals with epilepsy, dementia, and other mental disorders who require medication treatment and are unable to understand or follow the research protocol. Drug use, medical, psychological, or social conditions that may interfere with participants' participation in the study or evaluation of the results. Pregnant and lactating women. Patients who are accounted to be not appropriate for this trail by investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haiyan He, Master
Phone
+8613661513012
Email
doctorhehaiyan@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Du, Doctor
Organizational Affiliation
Shanghai Changzheng Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Du, Doctor
Phone
+86 02181885424
Email
Juan_du@live.com
First Name & Middle Initial & Last Name & Degree
Haiyan He, Master
Phone
+86 13661513012
Email
doctorhehaiyan@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Phase 2 Clinical Trial to Evaluate Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia

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