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

September 12, 2023 updated by: Juan Du, Shanghai Changzheng Hospital

A Prospective, Open-label, Multicenter Study of Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

60

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 Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200020
        • Recruiting
        • Shanghai Changzheng 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:

Subjects must meet all of the following criteria to be enrolled:

  1. Newly diagnosed patients with waldenström's macroglobulinemia meeting at least one criterion for treatment according to consensus panel criteria from the eleventh IWWM.
  2. ECOG score: 0-3 points, estimated survival time exceeding 3 months.
  3. Did not receive any treatment for Waldenström's macroglobulinemia before screening, except for glucocorticoid therapy for autoimmune hemolysis.
  4. 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.
  5. 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.
  6. No history of paroxysmal atrial fibrillation or chronic persistent atrial fibrillation.
  7. Able to swallow and Oral administration.
  8. The subjects complete all screening and evaluations listed in all trial protocols.
  9. The subjects who signed the informed consent form for chemotherapy.

Exclusion Criteria:

  1. Waldenström's macroglobulinemia with amyloidosis or POEM syndrome
  2. 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.
  3. Accompanied by other serious unstable diseases, including heart failure, renal failure, liver failure, hemorrhagic diseases, uncontrollable diabetes, etc.
  4. 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.
  5. Serious infectious diseases (uncured pulmonary tuberculosis, pulmonary aspergillosis, etc.).
  6. 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).
  7. Individuals with epilepsy, dementia, and other mental disorders who require medication treatment and are unable to understand or follow the research protocol.
  8. Drug use, medical, psychological, or social conditions that may interfere with participants' participation in the study or evaluation of the results.
  9. Pregnant and lactating women.
  10. Patients who are accounted to be not appropriate for this trail by investigator.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response
up to the end of 12 cycles of treatment(each cycle is 28 days)
The best deep response rate
Time Frame: Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
defined as 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)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Up to 6 years post first dose
PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.
Up to 6 years post first dose
Overall Survival (OS)
Time Frame: Up to 6 years post first dose
OS is measured from the date of the initial of treatment to the date of the subject's death.
Up to 6 years post first dose
minimal residual disease (MRD) rate
Time Frame: Up to 6 years post first dose
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.
Up to 6 years post first dose

Collaborators and Investigators

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

Sponsor

Shanghai Changzheng Hospital

Collaborators

RenJi Hospital
Huashan Hospital
Shanghai 6th People's Hospital
Huadong Hospital

Investigators

  • Principal Investigator: Juan Du, Doctor, Shanghai Changzheng 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)

August 1, 2023

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

July 30, 2023

First Submitted That Met QC Criteria

August 4, 2023

First Posted (Actual)

August 7, 2023

Study Record Updates

Last Update Posted (Actual)

September 14, 2023

Last Update Submitted That Met QC Criteria

September 12, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CZ-WM01

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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