Waldenström's MacroglobulinemiaPhase 2CZ-WM01NCT05979948
A Phase 2 Clinical Trial to Evaluate Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia
A Phase 2 study testing Zanubrutinib, Bendamustine and Rituximab in people with Waldenström's Macroglobulinemia, run by Shanghai Changzheng Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Waldenström's Macroglobulinemia
- What is being tested?
- Zanubrutinib, Bendamustine and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2023to 1 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, 200020
Juan Du, Doctor, +86 02181885424, Juan_du@live.com
Haiyan He, Master, +86 13661513012, doctorhehaiyan@126.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Waldenström's Macroglobulinemia
- Being tested
- Zanubrutinib, Bendamustine, Rituximab
- Keywords
- Waldenström's macroglobulinemia, Zanubrutinib, BR regimen, newly-diagnosed
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanubrutinibDrug
Zanubrutinib, 160 mg oral capsules twice daily for 12 months
BendamustineDrug
Bendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles.
RituximabDrug
Rituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| zanubrutinib combined with BR regimen | Experimental | 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. Receives: Drug: Zanubrutinib; Drug: Bendamustine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response
Measured: up to the end of 12 cycles of treatment(each cycle is 28 days)
The best deep response rate
defined as complete response (CR) and very good partial response (VGPR)
Measured: Time Frame: up to the end of 12 cycles of treatment(each cycle is 28 days)
Secondary outcomes (3)
Progression-free Survival (PFS)
PFS was defined as from the initiation of treatmentuntil to first documentation of progression or death, whichever comes first.
Measured: Up to 6 years post first dose
Overall Survival (OS)
OS is measured from the date of the initial of treatment to the date of the subject's death.
Measured: Up to 6 years post first dose
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.
Measured: Up to 6 years post first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2023
- Study start1 Aug 2023
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenström's MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by Shanghai Changzheng HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- RenJi Hospital, Huashan Hospital, Shanghai 6th People's Hospital, Huadong Hospital
- Responsible party
- Principal investigator, Juan Du, Shanghai Changzheng Hospital
- Investigators
- Juan Du, Doctor, Principal investigator, Shanghai Changzheng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05979948
- Sponsor's protocol ID
- CZ-WM01
- Acronym
- CZ-WM01
- Status last verified
- Sep 2023
- First submitted
- 30 Jul 2023
- Last updated
- 14 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open-label, Multicenter Study of Zanubrutinib Combined With BR (Bendamustine/Rituximab) Regimen in Subjects With Newly-diagnosed Waldenström's Macroglobulinemia
- ClinicalTrials.gov ID
- NCT05979948
- Acronym / sponsor ID
- CZ-WM01 / CZ-WM01
- Conditions
- Waldenström's Macroglobulinemia
- Keywords
- Waldenström's macroglobulinemia, Zanubrutinib, BR regimen, newly-diagnosed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Collaborators
- RenJi Hospital, Huashan Hospital, Shanghai 6th People's Hospital, Huadong Hospital
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 7 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| zanubrutinib combined with BR regimen | Experimental | Drug: Zanubrutinib, Drug: Bendamustine, Drug: RituximabDrug: 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanubrutinibZanubrutinib, 160 mg oral capsules twice daily for 12 months | Drug | zanubrutinib combined with BR regimen |
| BendamustineBendamustine, 70-90 mg/m2 on days 1 and 2 of each cycle for 6 cycles. | Drug | zanubrutinib combined with BR regimen |
| RituximabRituximab, 375 mg/m2 intravenously on day 0 of each cycle for 6 cycles | Drug | zanubrutinib combined with BR regimen |
Primary outcome
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
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)
3 secondary outcomes
Progression-free Survival (PFS)
Time frame: Up to 6 years post first dose
Overall Survival (OS)
Time frame: Up to 6 years post first dose
minimal residual disease (MRD) rate
Time frame: Up to 6 years post first dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Du, Doctor principal investigator
Shanghai Changzheng Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanubrutinib, Bendamustine and Rituximab in people with Waldenström's Macroglobulinemia, run by Shanghai Changzheng Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Haiyan He, Master (+8613661513012, doctorhehaiyan@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: up to the end of 12 cycles of treatment(each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2023.