Diffuse Large B-cell Lymphoma(DLBCL)Phase 2NCT05189197
A Study to Evaluate Efficacy and Safety of Zanubrutinib With R-CHOP in Newly Diagnosed Non-GCB DLBCL Patients With Double Expression
A Phase 2 study testing Zanubrutinib + R-CHOP in people with Diffuse Large B-cell Lymphoma(DLBCL), run by Fudan University at 1 site in China.
Trial summary
Zanubrutinib is a highly specific, potent new Bruton's tyrosine kinase （BTK） inhibitor, with minimal off-target inhibition of other kinases. This is a single-arm, open-label Phase II study to evaluate the efficacy and safety of zanubrutinib in combination with Rituximab, cyclophosphamide, doxorubicin, vincristine, and… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Diffuse Large B-cell Lymphoma(DLBCL)
- What is being tested?
- Zanubrutinib + R-CHOP
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteChina
- Study dates
- 18 Jan 2022to Jan 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject must be 18 years of age or older.
- No prior treatment for DLBCL.
- Histologically - confirmed non-GCB subtype.
- MYC+≥40% and BCL2+≥50% by IHC
- Lesions must be measurable. A measurable node lesion must have a longest diameter greater than 1.5 cm. A measurable extra-nodal lesion should have a longest diameter greater than 1.0 cm.
- Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2
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- Stage II (not candidates for local X-ray therapy), III, or IV disease by the Ann Arbor Classification
- Hematology values must be within the following limits at baseline:
- Neutrophils ≥ 1 x 109/L, independent of growth factor support within 7 days of initiation of the combination therapy.
- Platelets ≥ 75x 109/L, independent of growth factor support or transfusion within 7 days of initiation of the combination therapy. (platelets≥ 50 x 109/L, if there is bone marrow involvement.)
- Biochemical values must be within the following limits at baseline:
- Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤3 x ULN.
- Total bilirubin ≤1.5 x ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
- Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate≥40 mL/min/1.73m2
- International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 x ULN.
- Able to provide written informed consent, can understand and comply breastfeeding are ineligible for this study.
Who cannot join
- Primary mediastinal lymphoma.
- Central nervous system involvement lymphoma.
- Histologically transformed lymphoma.
- Diagnosed or treated for malignancies other than DLBCL.
- History of stroke or intracranial hemorrhage within 6 months.
- Major surgery within 4 weeks.
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- Required ongoing treatment with medication that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong/median effect CYP3A inducers.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, 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 Echocardiography: Left ventricular ejection fraction (LVEF) < 50%
- Active, clinically significant Electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block Type II, or third-degree AV block or QT interval corrected for heart rate (QTcF) prolongation, defined as a QTcF > 450 msec.
- Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
- Known human immunodeficiency virus (HIV) infection, or active hepatitis B or hepatitis C infection.
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of zanubrutinib capsules, or put the study outcomes at undue risk.
- Pregnant or lactating women.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Zanubrutinib in Combination With R-CHOP in Newly Diagnosed Non-GCB DLBCL Patients With Double Expression: A Single-arm, Open-label, Phase II Study
Zanubrutinib is a highly specific, potent new Bruton's tyrosine kinase （BTK） inhibitor, with minimal off-target inhibition of other kinases. This is a single-arm, open-label Phase II study to evaluate the efficacy and safety of zanubrutinib in combination with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in newly diagnosed non-GCB Diffuse large B-cell lymphoma (DLBCL) patients with co-expression of B-cell lymphoma 2 （BCL2）and myelocytomatosis oncogene（MYC）.
Read the detailed description
Diffuse large B-cell lymphoma as the most common lymphoma, is heterogeneous. R-CHOP is the standard care in front-line DLBCL treatment. However, there are still about 40% of the DLBCL patients treated with R-CHOP relapse or respond poorly.
There are 20%-30% DLBCL patients having BCL2 and MYC co-expression, which are more common in activated B -cell-like（ABC）-DLBCL. Previous study showed that patients with co-expression of BCL2 and MYC by immunohistochemistry (IHC) have a worse outcome with R-CHOP.
Efficacy results from Studies PCYC-04753 and PCYC-1106-CA demonstrate that BTK inhibitor ibrutinib has some activity as a single agent in subjects with relapsed or refractory DLBCL, with possible lower response rates in subjects with the germinal center B-cell-like （GCB）subtype.
In post hoc of PHEONIX study, non-GCB subgroup pts with MYC-high + BCL2-high had better event free survival （EFS ）(HR 0.648; 95% confidence interval （CI), 0.423-0.993; p = 0.045) with ibrutinib + R-CHOP versus placebo + R-CHOP.
Zanubrutinib is a highly specific, potent new BTK inhibitor, with minimal off-target inhibition of other kinases, and is associated with better tolerability, compared with ibrutinib. A post hoc analysis on 4 studies found that Patients with MYC and BCL2 double-expressor DLBCL resulted in objective response rate（ORR）of 61% and progression free survival (PFS) of 5.4m when treated with zanubrutinib. However, it is still unknown the benefit of zanubrutinib and RCHOP combination therapy followed by zanubrutinib maintenance in non-GCB DLBCL patients with co-expression of BCL2 and MYC.
This is a single-arm, phase II study, to evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP followed by zanubrutinib maintenance in newly diagnosed non-GCB subtype of DLBCL patients with MYC-high + BCL2-high selected by IHC.
The study will include a Screening Phase, Combination Treatment Phase, Maintenance phase and a Post Treatment Follow-up Phase.
- Conditions
- Diffuse Large B-cell Lymphoma(DLBCL)
- Being tested
- Zanubrutinib + R-CHOP
- Keywords
- Diffuse large B-cell lymphoma, Zanubrutinib
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zanubrutinib + R-CHOPDrug
Also called Brukinsa+Mabthera +CHOP
Zanubrutinib 160 mg BID administered by oral every day of each 21-day cycle. Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 (maximum total 2 mg) administered by IV infusion on Day 1 of each 21-day cycle.
Prednisone 100 mg administered by oral on Day 1-5 of each 21-day cycle. After 6 cycles of zanubrutinib and R-CHOP combination therapy, patients achieved CR will continue to receive zanubrutinib 160mg BID for 1 year.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Zanubrutinib + R-CHOP | Experimental | Zanubrutinib 160 mg bis in die（BID） administered by oral every day of each 21-day cycle. Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 (maximum total 2 mg) administered by IV infusion on Day 1 of each 21-day cycle.
Prednisone 100 mg administered by oral on Day 1-5 of each 21-day cycle. After 6 cycles of zanubrutinib and R-CHOP combination therapy, patients achieved complete response （CR）will continue to receive zanubrutinib 160mg BID for 1 year. Receives: Drug: Zanubrutinib + R-CHOP |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year event-free survival (EFS) rate
3-year EFS rate is defined as the proportion of patients free from EFS events at 3 years after the initiation of zanubrutinib and RCHOP combination therapy estimated using the Kaplan-Meier method. EFS is defined as the duration from the initiation of zanubrutinib and RCHOP combination therapy to the date of documented disease progression, relapse from CR, initiation of subsequent systemic anti-lymphoma therapy for either positron emission computed tomography (PET)-positive or biopsy-proven residual disease after six cycles of Zanubrutinib and R-CHOP combination therapy, or any-cause death whichever occurs first.
Measured: up to 3 years
Secondary outcomes (5)
Overall response rate (ORR)
ORR is defined as the proportion of patients achieving complete response (CR) and partial response (PR), as per Lugano Classification.
Measured: up to 18 weeks
Complete response rate (CRR)
CRR is defined as proportion of patients achieving CR, as determined per Lugano Classification.
Measured: up to 18 weeks
3-year progression-free survival rate （PFS)
3-year PFS rate is defined as the proportion of patients free from PFS events at 3 years after the initiation of zanubrutinib and RCHOP combination therapy estimated using the Kaplan-Meier method. PFS is defined as the duration from the initiation of zanubrutinib and RCHOP combination therapy to the date of disease progression, relapse from CR, or death, whichever occurs first.
Measured: up to 3 years
3-year overall survival (OS) rate
3-year OS rate is defined as the proportion of patients alive at 3 years after the initiation of zanubrutinib and RCHOP combination therapy estimated using the Kaplan-Meier method. OS is defined as the duration from the date of initiation of zanubrutinib and RCHOP combination therapy to the date of death.
Measured: up to 3 years
adverse event（AE）
The incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse event（SAEs）and reatment-related AEs according to CTCAE v5.0
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2022
- Study start18 Jan 2022
- Primary completionJan 2025 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-cell Lymphoma(DLBCL)Studies of the same condition, open and under way.
- More trials run by Fudan 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
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Baotou Cancer Hospital, Xiangya Hospital of Central South University, Shanghai Changzheng Hospital
- Responsible party
- Principal investigator, Junning Cao, MD, Fudan University
- Investigators
- Junning Cao, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05189197
- Sponsor's protocol ID
- ZRCHOP-BGB-3111-2004-IIT
- Status last verified
- May 2024
- First submitted
- 29 Dec 2021
- Last updated
- 17 May 2024
- Results posted
- 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 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Zanubrutinib in Combination With R-CHOP in Newly Diagnosed Non-GCB DLBCL Patients With Double Expression: A Single-arm, Open-label, Phase II Study
- ClinicalTrials.gov ID
- NCT05189197
- Acronym / sponsor ID
- ZRCHOP-BGB-3111-2004-IIT
- Conditions
- Diffuse Large B-cell Lymphoma(DLBCL)
- Keywords
- Diffuse large B-cell lymphoma, Zanubrutinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Collaborators
- Baotou Cancer Hospital, Xiangya Hospital of Central South University, Shanghai Changzheng Hospital
- Study start
- 18 Jan 2022 (actual)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 12 Jan 2022 (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.
Zanubrutinib is a highly specific, potent new Bruton's tyrosine kinase （BTK） inhibitor, with minimal off-target inhibition of other kinases. This is a single-arm, open-label Phase II study to evaluate the efficacy and safety of zanubrutinib in combination with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in newly diagnosed non-GCB Diffuse large B-cell lymphoma (DLBCL) patients with co-expression of B-cell lymphoma 2 （BCL2）and myelocytomatosis oncogene（MYC）.
Detailed description
Diffuse large B-cell lymphoma as the most common lymphoma, is heterogeneous. R-CHOP is the standard care in front-line DLBCL treatment. However, there are still about 40% of the DLBCL patients treated with R-CHOP relapse or respond poorly.
There are 20%-30% DLBCL patients having BCL2 and MYC co-expression, which are more common in activated B -cell-like（ABC）-DLBCL. Previous study showed that patients with co-expression of BCL2 and MYC by immunohistochemistry (IHC) have a worse outcome with R-CHOP.
Efficacy results from Studies PCYC-04753 and PCYC-1106-CA demonstrate that BTK inhibitor ibrutinib has some activity as a single agent in subjects with relapsed or refractory DLBCL, with possible lower response rates in subjects with the germinal center B-cell-like （GCB）subtype.
In post hoc of PHEONIX study, non-GCB subgroup pts with MYC-high + BCL2-high had better event free survival （EFS ）(HR 0.648; 95% confidence interval （CI), 0.423-0.993; p = 0.045) with ibrutinib + R-CHOP versus placebo + R-CHOP.
Zanubrutinib is a highly specific, potent new BTK inhibitor, with minimal off-target inhibition of other kinases, and is associated with better tolerability, compared with ibrutinib. A post hoc analysis on 4 studies found that Patients with MYC and BCL2 double-expressor DLBCL resulted in objective response rate（ORR）of 61% and progression free survival (PFS) of 5.4m when treated with zanubrutinib. However, it is still unknown the benefit of zanubrutinib and RCHOP combination therapy followed by zanubrutinib maintenance in non-GCB DLBCL patients with co-expression of BCL2 and MYC.
This is a single-arm, phase II study, to evaluate the efficacy and safety of zanubrutinib in combination with R-CHOP followed by zanubrutinib maintenance in newly diagnosed non-GCB subtype of DLBCL patients with MYC-high + BCL2-high selected by IHC.
The study will include a Screening Phase, Combination Treatment Phase, Maintenance phase and a Post Treatment Follow-up Phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Zanubrutinib + R-CHOP | Experimental | Drug: Zanubrutinib + R-CHOPZanubrutinib 160 mg bis in die（BID） administered by oral every day of each 21-day cycle. Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 (maximum total 2 mg) administered by IV infusion on Day 1 of each 21-day cycle. Prednisone 100 mg administered by oral on Day 1-5 of each 21-day cycle. After 6 cycles of zanubrutinib and R-CHOP combination therapy, patients achieved complete response （CR）will continue to receive zanubrutinib 160mg BID for 1 year. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Subject must be 18 years of age or older.
- No prior treatment for DLBCL.
- Histologically - confirmed non-GCB subtype.
- MYC+≥40% and BCL2+≥50% by IHC
- Lesions must be measurable. A measurable node lesion must have a longest diameter greater than 1.5 cm. A measurable extra-nodal lesion should have a longest diameter greater than 1.0 cm.
Key exclusion criteria (13 listed)
- Primary mediastinal lymphoma.
- Central nervous system involvement lymphoma.
- Histologically transformed lymphoma.
- Diagnosed or treated for malignancies other than DLBCL.
- History of stroke or intracranial hemorrhage within 6 months.
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 |
|---|---|---|
| Zanubrutinib + R-CHOPAlso: Brukinsa+Mabthera +CHOPZanubrutinib 160 mg BID administered by oral every day of each 21-day cycle. Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 (maximum total 2 mg) administered by IV infusion on Day 1 of each 21-day cycle. Prednisone 100 mg administered by oral on Day 1-5 of each 21-day cycle. After 6 cycles of zanubrutinib and R-CHOP combination therapy, patients achieved CR will continue to receive zanubrutinib 160mg BID for 1 year. | Drug | Experimental: Zanubrutinib + R-CHOP |
Primary outcome
3-year event-free survival (EFS) rate
Time frame: up to 3 years
3-year EFS rate is defined as the proportion of patients free from EFS events at 3 years after the initiation of zanubrutinib and RCHOP combination therapy estimated using the Kaplan-Meier method. EFS is defined as the duration from the initiation of zanubrutinib and RCHOP combination therapy to the date of documented disease progression, relapse from CR, initiation of subsequent systemic anti-lymphoma therapy for either positron emission computed tomography (PET)-positive or biopsy-proven residual disease after six cycles of Zanubrutinib and R-CHOP combination therapy, or any-cause death whichever occurs first.
5 secondary outcomes
Overall response rate (ORR)
Time frame: up to 18 weeks
Complete response rate (CRR)
Time frame: up to 18 weeks
3-year progression-free survival rate （PFS)
Time frame: up to 3 years
3-year overall survival (OS) rate
Time frame: up to 3 years
adverse event（AE）
Time frame: up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- 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.
Junning Cao principal investigator
Fudan University
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 + R-CHOP in people with Diffuse Large B-cell Lymphoma(DLBCL), run by Fudan 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 16 inclusion and 13 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 17 May 2024. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year event-free survival (EFS) rate (time frame: up to 3 years). 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 17 May 2024.