Mantle Cell LymphomaPhase 2NCT04736914
Zanubrutinib-based Induction and Maintenance Therapy in Young and Fit Patients With Untreated Mantle Cell Lymphoma
A Phase 2 study testing R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance） in people with Mantle Cell Lymphoma, run by Sun Yat-sen University at 1 site in China.
Trial summary
This is a prospective, single-center, single-arm, phase II study of Zanubrutinib-based induction followed by ASCT and Zanubrutinib maintenance (2 years) or followed directly by Zanubrutinib maintenance without ASCT in young and fit patients with untreated MCL. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance）
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteChina
- Study dates
- 31 Jan 2021to 28 Feb 2026
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Histologically confirmed diagnosis of MCL according to WHO classification
- Previously untreated MCL
- Suitable for high-dose treatment including high-dose Ara-C
- Age ≥ 18 years and ≤ 65 years
- Stage II-IV (Ann Arbor)
- Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI). Measurable disease was defined as at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions; in case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations
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- ECOG performance status ≤ 2
- The following laboratory values at screening (unless related to MCL):
- Absolute neutrophil count (ANC) ≥ 1×10⁹/L
- Platelets ≥ 75×10⁹/L (platelets ≥ 50×10⁹/L with bone marrow involvement)
- Transaminases (AST and ALT) ≤ 3 × upper limit of normal (ULN)
- Total bilirubin ≤ 2 × ULN (unless documented Gilbert's syndrome)
- Calculated creatinine clearance ≥ 30 mL/min
- International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x upper limit of normal. If a factor inhibitor was present with prolongation of the international normalized ratio or activated partial thromboplastin time.
- Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug
- Life expectancy of> 3 months
- Written informed consent form according to GCP and national regulations
Who cannot join
- Known CNS involvement of MCL
- Major surgery within 4 weeks of screening
- Prior hematopoietic stem cell transplantation
- Concomitant or previous malignancies within the last 2 years other than basal cell skin cancer or in situ uterine cervix cancer
- Clinically significant cardiovascular disease such as uncontrolled arrhythmias and hypertension , congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below 50%（AHA，2016）
- QTcF > 450 msec or other significant electrocardiogram (ECG) abnormalities including second-degree atrioventricular block Type II, or third-degree atrioventricular block
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- Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of zanubrutinib itself or to the excipients in its formulation)
- Requires treatment with strong CYP3A inhibitors or strong CYP3A inducers
- Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- Patients with unresolved hepatitis B or C infection or known HIV positive infection
- Active infection including infections requiring oral or intravenous antimicrobial therapy
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk
- History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
- Pregnancy or lactation
- Participation in another clinical trial within 30 days before enrollment in this study
- poor compliance
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Medical Oncology, Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Huiqiang Huang, Professor, +86 020 87343350, huanghq@sysucc.org.cn
Huiqiang Huang
About this study
Official title: A Perspective Study of Zanubrutinib-based Induction and Maintenance Therapy in Young and Fit Patients With Untreated Mantle Cell Lymphoma (BRIDGE)
This is a prospective, single-center, single-arm, phase II study of Zanubrutinib-based induction followed by ASCT and Zanubrutinib maintenance (2 years) or followed directly by Zanubrutinib maintenance without ASCT in young and fit patients with untreated MCL.
There will be an initial safety run-in phase of 6 patients which will be closely monitored for the observed toxicities during cycle1 in， induction therapy. After completion of safety run-in phase, the investigator will assessed and decided whether to continue the trial as planned. If no unexpected toxicity has been observed, study will expand the sample size to further assess efficacy and safety.
Read more
Total around 47 patients aged 18-65 years with previously untreated, Ann Arbor stage II-IV, histologically proven MCL will be enrolled to receive alternating 3 cycles R-CHOP + Zanubrutinib /3 cycles R-DHAOx induction. Totally 6 cycles in induction and every 21 days per cycle. Due to lack of published data about BTKi in combination with R-DHAOx, Zanubrutinib is only applied in cycle 1,3,5(R-CHOP), 160mg BID, d1-21, and not in combination with R-DHAOx
Patients who achieve remission (≥PR) will be allowed to proceed to ASCT or maintenance. Whether ASCT or not depends on investigator's evaluation and discretion. In patients who do not achieve a remission at end of induction (treatment failure), no study specific treatment is defined; rather, the further salvage treatment is upon the discretion of investigators. Patients remain in study for progression and survival follow-up.
Patients will receive Zanubrutinib maintenance for two years in case of remission at ASCT assessment or end of induction assessment. Zanubrutinib is applied oral 160mg BID, continuously for 2 year or until progressive disease, unacceptable toxicity or death, whichever comes first.
The primary analysis will be performed after last-patient completes induction treatment.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance）
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance）Drug
Also called R-CHOP，R-DHAOx，Brukinsa
Alternating 3× R-CHOP/ 3× R-DHAOx, every 21 days plus oral Zanubrutinib in cycle 1, 3, 5 in combination with R-CHOP:
R-CHOP (cycle 1,3,5):
Rituximab 375 mg/m2 D1, I.V. Cyclophosphamide 750 mg/m2 D1, I.V. Doxorubicine 50 mg/m2 D1, I.V. Vincristine 1.4mg/m2(max 2mg)D1, I.V. Prednisone 100mg D1-5, oral Zanubrutinib 160mg BID D1-21, oral
R-DHAOx (cycle 2,4,6):
Dexamethasone 40mg D1-4 oral/I.V. Rituximab 375mg/m2 D1, I.V. Ara-C 2×2g/m2 q12h D2, I.V. Cisplatin 100mg/m2 D1, I.V.
Maintenance:
- Zanubrutinib, 160mg PO BID, continuously for 2 year or until progressive disease。
- Zanubrutinib maintenance will start after regeneration of peripheral blood count after the end of the last cycle of induction therapy or ASCT
| Study group | Role | What they receive |
|---|---|---|
| Zanubrutinib+R-CHOP/R-DHAOx | Experimental | Induction:
Alternating 3× R-CHOP/ 3× R-DHAOx, every 21 days plus oral Zanubrutinib in cycle 1, 3, 5 in combination with R-CHOP:
ASCT conditioning
Maintenance:
* Zanubrutinib, 160mg PO BID, continuously for 2 year
* Zanubrutinib maintenance will start after regeneration of peripheral blood count after the end of the last cycle of induction therapy or ASCT
Requirements for start of maintenance:
* ANC ≥ 1,000 cells/mm³ (1.0 X 109/L);
* Platelets ≥ 50,000 cells/mm³ (50 X 109/L); Receives: Drug: R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance） |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRD negativity rate
To evaluate the MRD negativity rate after Zanubrutinib-based induction therapy in subjects with newly diagnosed, young and fit MCL.
The primary endpoint of the trial will be bone marrow minimal residual disease (MRD) negative rate after induction therapy (at the completion of cycle 6 or at premature discontinuation).
Measured: 18 weeks
Secondary outcomes (3)
Duration of MRD negativity
The time from the first achieving MRD negativity after start of treatment to the MRD convert to positive
Measured: 60 months
Progression free survival (PFS)
The time from start of treatment to progression or death from any cause
Measured: 60 months
Overall survival (OS)
The time from start of treatment to death from any cause
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start31 Jan 2021
- Primary completion31 Jan 2023 (estimated)
- Study completion28 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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
- Model description
- Zanubrutinib Combined with R-CHOP，R-DHAOx
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Huiqiang Huang, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04736914
- Sponsor's protocol ID
- BGB-3111-2002-IIT
- Status last verified
- Aug 2021
- First submitted
- 1 Feb 2021
- Last updated
- 26 Aug 2021
- 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 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Perspective Study of Zanubrutinib-based Induction and Maintenance Therapy in Young and Fit Patients With Untreated Mantle Cell Lymphoma (BRIDGE)
- ClinicalTrials.gov ID
- NCT04736914
- Acronym / sponsor ID
- BGB-3111-2002-IIT
- Conditions
- Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 31 Jan 2021 (actual)
- Primary completion
- 31 Jan 2023 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 3 Feb 2021 (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 is a prospective, single-center, single-arm, phase II study of Zanubrutinib-based induction followed by ASCT and Zanubrutinib maintenance (2 years) or followed directly by Zanubrutinib maintenance without ASCT in young and fit patients with untreated MCL.
There will be an initial safety run-in phase of 6 patients which will be closely monitored for the observed toxicities during cycle1 in， induction therapy. After completion of safety run-in phase, the investigator will assessed and decided whether to continue the trial as planned. If no unexpected toxicity has been observed, study will expand the sample size to further assess efficacy and safety.
Total around 47 patients aged 18-65 years with previously untreated, Ann Arbor stage II-IV, histologically proven MCL will be enrolled to receive alternating 3 cycles R-CHOP + Zanubrutinib /3 cycles R-DHAOx induction. Totally 6 cycles in induction and every 21 days per cycle. Due to lack of published data about BTKi in combination with R-DHAOx, Zanubrutinib is only applied in cycle 1,3,5(R-CHOP), 160mg BID, d1-21, and not in combination with R-DHAOx
Patients who achieve remission (≥PR) will be allowed to proceed to ASCT or maintenance. Whether ASCT or not depends on investigator's evaluation and discretion. In patients who do not achieve a remission at end of induction (treatment failure), no study specific treatment is defined; rather, the further salvage treatment is upon the discretion of investigators. Patients remain in study for progression and survival follow-up.
Patients will receive Zanubrutinib maintenance for two years in case of remission at ASCT assessment or end of induction assessment. Zanubrutinib is applied oral 160mg BID, continuously for 2 year or until progressive disease, unacceptable toxicity or death, whichever comes first.
The primary analysis will be performed after last-patient completes induction treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Zanubrutinib Combined with R-CHOP，R-DHAOx
| Arm | Type | Receives |
|---|---|---|
| Zanubrutinib+R-CHOP/R-DHAOx | Experimental | Drug: R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance）Induction: Alternating 3× R-CHOP/ 3× R-DHAOx, every 21 days plus oral Zanubrutinib in cycle 1, 3, 5 in combination with R-CHOP: ASCT conditioning Maintenance: * Zanubrutinib, 160mg PO BID, continuously for 2 year * Zanubrutinib maintenance will start after regeneration of peripheral blood count after the end of the last cycle of induction therapy or ASCT Requirements for start of maintenance: * ANC ≥ 1,000 cells/mm³ (1.0 X 109/L); * Platelets ≥ 50,000 cells/mm³ (50 X 109/L); |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 1. Histologically confirmed diagnosis of MCL according to WHO classification
- Previously untreated MCL
- Suitable for high-dose treatment including high-dose Ara-C
- Age ≥ 18 years and ≤ 65 years
- Stage II-IV (Ann Arbor)
Key exclusion criteria (16 listed)
- Known CNS involvement of MCL
- Major surgery within 4 weeks of screening
- Prior hematopoietic stem cell transplantation
- Concomitant or previous malignancies within the last 2 years other than basal cell skin cancer or in situ uterine cervix cancer
- Clinically significant cardiovascular disease such as uncontrolled arrhythmias and hypertension , congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below 50%（AHA，2016）
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 |
|---|---|---|
| R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance）Also: R-CHOP，R-DHAOx，BrukinsaAlternating 3× R-CHOP/ 3× R-DHAOx, every 21 days plus oral Zanubrutinib in cycle 1, 3, 5 in combination with R-CHOP: R-CHOP (cycle 1,3,5): Rituximab 375 mg/m2 D1, I.V. Cyclophosphamide 750 mg/m2 D1, I.V. Doxorubicine 50 mg/m2 D1, I.V. Vincristine 1.4mg/m2(max 2mg)D1, I.V. Prednisone 100mg D1-5, oral Zanubrutinib 160mg BID D1-21, oral R-DHAOx (cycle 2,4,6): Dexamethasone 40mg D1-4 oral/I.V. Rituximab 375mg/m2 D1, I.V. Ara-C 2×2g/m2 q12h D2, I.V. Cisplatin 100mg/m2 D1, I.V. Maintenance: * Zanubrutinib, 160mg PO BID, continuously for 2 year or until progressive disease。 * Zanubrutinib maintenance will start after regeneration of peripheral blood count after the end of the last cycle of induction therapy or ASCT | Drug | Zanubrutinib+R-CHOP/R-DHAOx |
Primary outcome
MRD negativity rate
Time frame: 18 weeks
To evaluate the MRD negativity rate after Zanubrutinib-based induction therapy in subjects with newly diagnosed, young and fit MCL. The primary endpoint of the trial will be bone marrow minimal residual disease (MRD) negative rate after induction therapy (at the completion of cycle 6 or at premature discontinuation).
3 secondary outcomes
Duration of MRD negativity
Time frame: 60 months
Progression free survival (PFS)
Time frame: 60 months
Overall survival (OS)
Time frame: 60 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2021.
- 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.
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 R-CHOP/R-DHAOx； Zanubrutib（induction）； ASCT conditioning ； Zanubrutinib（Maintenance） in people with Mantle Cell Lymphoma, run by Sun Yat-sen University 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 17 inclusion and 16 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 26 Aug 2021. 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 huang huiqiang (138 0888 5154, haunghq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRD negativity rate (time frame: 18 weeks). 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 26 Aug 2021.