BTK InhibitorsPhase 2NCT06890585
Zanubrutinib, Chidamide, and Rituximab Induction With or Without CHOP Versus R-CHOP in Newly Diagnosed Double-Expressor DLBCL
A Phase 2 study testing ZCR-CHOP and R-CHOP in people with BTK Inhibitors and Histone Deacetylase Inhibitor, run by Li Zhiming at 1 site in China.
Trial summary
Zanubrutinib, as a new generation of BTK inhibitors, has shown more potent antitumor activity and lower adverse reactions than ibrutinib in head-to-head clinical studies, which make it a promising regimen for B cell lymphoma. Chidamide is an oral subtype-selective histone deacetylase inhibitor. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- BTK Inhibitors, Histone Deacetylase Inhibitor, Double Express Diffuse Large B-cell Lymphoma
- What is being tested?
- ZCR-CHOP and 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
- 128 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2025to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Newly diagnosed MYC/BCL2 double-expressor DLBCL confirmed by pathological histology/clinical imaging, with IHC BCL2 expression ≥50% and MYC expression ≥40%.
- Male or female patients aged 18-65 years.
- ECOG score of 0-2.
- Expected survival time of ≥6 months.
- Must have at least one evaluable or measurable lesion according to the Lugano 2014 criteria [Evaluable lesion: lymph node or extranodal local uptake increased (higher than the liver) on 18F-Fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) scan, and PET and/or Computed Tomography (CT) features consistent with lymphoma; Measurable lesion: nodal lesion with a long diameter >15mm or extranodal lesion with a long diameter >10mm, with increased 18FDG uptake]. Patients with no measurable lesions and diffuse 18FDG uptake in the liver should be excluded.
- Good major organ function, meeting the following requirements within one week before enrollment: blood routine WBC ≥3×10^9/L, Hb ≥80g/L, PLT ≥80×10^9/L; normal cardiac and liver function (total bilirubin ≤1.5 times the upper limit of normal, ALT and AST ≤2.5 times the upper limit of normal), normal renal function (serum creatinine ≤1.5 times the upper limit of normal), and no coagulation abnormalities.
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- LVEF ≥50% as measured by echocardiography.
- Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and be willing to use reliable contraception during the study.
- Subjects voluntarily join the study, sign the informed consent form, have good compliance, and cooperate with follow-up.
Who cannot join
- Special types of DLBCL:Fluid overload-associated large B-cell lymphoma, primary mediastinal large B-cell lymphoma, mediastinal gray zone lymphoma, primary central nervous system (CNS) DLBCL, double-hit DLBCL with BCL2 and MYC rearrangements.
- Transformed DLBCL (e.g., DLBCL transformed from follicular lymphoma, chronic lymphocytic leukemia/small B-cell lymphoma), secondary CNS involvement of DLBCL.
- History of other malignancies within the past 5 years, except for squamous cell carcinoma of the skin, basal cell carcinoma of the skin, and carcinoma in situ of the cervix.
- Major surgery within the past 2 months (excluding diagnostic surgery).
- Previous treatment for NHL, including chemotherapy, immunotherapy, radiotherapy, monoclonal antibody therapy, or surgical treatment (excluding diagnostic surgery and biopsy).
- Previous treatment with cytotoxic drugs or anti-CD20 monoclonal antibody therapy for other diseases (e.g., rheumatoid arthritis).
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- Use of any monoclonal antibody within 3 months prior to enrollment, participation in other clinical trials with investigational drugs, or vaccination with live attenuated virus vaccines within 1 month prior to enrollment.
- Use of hematopoietic growth factors within 2 weeks prior to enrollment.
- Suspected active or latent tuberculosis.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections (excluding nail bed fungal infections) within 4 weeks prior to enrollment, or any major systemic infection requiring intravenous antibiotics or hospitalization (excluding tumor fever).
- History of severe bleeding disorders, such as hemophilia A, hemophilia B, von Willebrand disease, or spontaneous bleeding requiring transfusion or other medical intervention.
- HIV-positive patients. Active HBV-positive and HCV-positive patients, but those with controlled conditions as judged by the investigator may be cautiously enrolled with effective antiviral intervention.
- Other severe diseases that may limit participation in this trial, such as uncontrolled diabetes; severe heart failure (NYHA class II or above); acute coronary syndrome within the past 6 months; coronary revascularization within the past 6 months, such as stent implantation, coronary artery bypass grafting, and other heart and large vessel surgeries; severe arrhythmias including frequent premature ventricular contractions, ventricular tachycardia, rapid atrial fibrillation/flutter, severe bradycardia. Uncontrolled hypertension (greater than 150/100 mmHg). Gastric ulcer (with a risk of perforation as judged by the investigator); active autoimmune diseases; severe hypertension; severe respiratory diseases (e.g., obstructive pulmonary disease and bronchospasm history), such as known interstitial pneumonia or highly suspected interstitial pneumonia; or patients who may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Contraindications to any study drug, including previous treatment with anthracyclines; patients with diabetes who cannot tolerate prednisone treatment in this regimen.
- History of alcohol abuse or drug abuse.
- Allergic constitution, or known allergy to any active ingredient, excipient, or murine products, heterologous proteins included in this study.
- Requirement for continuous treatment with strong CYP3A inhibitors or inducers (see Appendix 6).
- Severe mental illness.
- Patients unable to comply with the study and/or follow-up phases.
- Patients unable to swallow study drugs normally.
- Patients deemed unsuitable for enrollment by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Zhiming Li, M.D., +86-020-87343350, lizhm@sysucc.org.cn
Peng Sun, M.D., sunp@sysucc.org.cn
About this study
Official title: A Randomized, Multicenter, Open-Label Phase II Clinical Study Comparing the Efficacy and Safety of Zanubrutinib, Chidamide, and Rituximab Induction Therapy Sequentially Combined With or Without CHOP Versus R-CHOP in the First-Line Treatment of Patients With Newly Diagnosed Double-Expressor Diffuse Large B-cell Lymphoma
Zanubrutinib, as a new generation of BTK inhibitors, has shown more potent antitumor activity and lower adverse reactions than ibrutinib in head-to-head clinical studies, which make it a promising regimen for B cell lymphoma. Chidamide is an oral subtype-selective histone deacetylase inhibitor.
This Randomized, Multicenter, Open-Label Phase II Clinical Study is comparing the efficacy and safety of Zanubrutinib, Chidamide, and Rituximab induction therapy sequentially combined with or without CHOP versus R-CHOP in the first-line treatment of patients with newly diagnosed double-expressor DLBCL.
Read the detailed description
This study is designed to compare the efficacy and safety of zanubrutinib, chidamide, and rituximab (ZCR) induction therapy sequentially combined with or without CHOP regimen versus the standard R-CHOP regimen as first-line treatment for newly diagnosed double-expressor DLBCL. This study targets patients with MYC/BCL2 double-expressing DLBCL, a group with poor prognosis under traditional R-CHOP treatment.
The study consists of screening period, treatment period, and follow-up period, with subjects randomly assigned to the experimental group and the control group in a 1:1 ratio. The primary endpoint is the end-of-treatment complete response rate (EOT-CRR), while secondary endpoints include the overall response rate (EOT-ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A total of 128 patients are planned to be enrolled.
Efficacy evaluation will be conducted using the 2014 Lugano criteria, with imaging examinations such as PET-CT to objectively measure treatment response. adverse events (AEs) throughout the entire trial and grade the severity of adverse events will be recorded according to the guidelines of the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) 5.0.
- Conditions
- BTK Inhibitors, Histone Deacetylase Inhibitor, Double Express Diffuse Large B-cell Lymphoma
- Being tested
- ZCR-CHOP, R-CHOP
- Keywords
- Double Expressor Diffuse Large B-cell Lymphoma, zanubrutinib, chidamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZCR-CHOPDrug
Zanubrutinib, Chidamide, and Rituximab Induction Therapy Sequentially Combined With or Without CHOP
R-CHOPDrug
R-CHOP
| Study group | Role | What they receive |
|---|---|---|
| ZCR-CHOP | Experimental | Cycle 1-2 Drug: Zanubrutinib Zanubrutinib will be given at a dose of 160mg，bid，from d1 to d21 in a 21-day cycle Drug: Chidamide Chidamide will be given at a dose of 20 mg after breakfast on day 1, day 4, day 8, day 11 in a 21-day cycle Drug: Rituximab Rituximab will be given at a dose of 375 mg/m2 by IV on day 1 in a 21-day cycle
Cycle 3-8 Patients who achieve complete response evaluated by PEC-CT per Lugano 2014 criteria after two course of treatment will continue to take Zanubrutinib, chidamide, and rituximab for up to 8 cycles in total.
Patients who achieve partial response and stable disease will take ZCR combined with CHOP or up to 8 cycles in total.
CHOP : cyclophosphamide 750 mg/m2 IV D1, Doxorubicin/Epirubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 IV [maximum total 2 mg], and prednisone 30 mg orally tid from d1 to d5 in a 21-day cycle Receives: Drug: ZCR-CHOP |
| R-CHOP | Active comparator | R-CHOP Rituximab 375 mg/m2 IV on d1, cyclophosphamide 750 mg/m2 IV on d1, Doxorubicin/Epirubicin 50 mg/m2 IV on d1, vincristine 1.4 mg/m2 IV [maximum total 2 mg] on d1, and prednisone 30 mg orally tid from d1 to d5 in a 21-day cycle for up to 6 cycles. Receives: Drug: R-CHOP |
What is being measured
The primary outcome is the main question the study is designed to answer.
EOT-CR
defined as the proportion of subjects with measurable disease who achieve CR at the end of treatment according to 2014 Lugano criteria
Measured: Approximately 12 months
Secondary outcomes (5)
EOT-ORR
defined as the proportion of subjects with measurable disease who achieve CR and PR at the end of treatment according to 2014 Lugano criteria
Measured: Approximately 12 months
Duration of response（DOR）
defined as the time from the date of first occurrence of CR or PR to the date of the first documented PD or death due to any cause according to 2014 Lugano criteria.
Measured: Approximately 24 months
Progression-free survival (PFS)
defined as the time from treatment to disease progression or death from any cause according to 2014 Lugano criteria.
Measured: Approximately 24 months
Overall survival (OS)
defined as the time from treatment to death from any cause according to 2014 Lugano criteria.
Measured: Approximately 24 months
Adverse Events (AE)
all adverse events occurring during or after the first treatment will be summarized by treatment arm and NCI CTCAE grade.
Measured: Approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2025
- Study start1 Jun 2025 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BTK InhibitorsStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Li Zhiming
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Li Zhiming, Sun Yat-sen University
- Investigators
- Zhiming Li, M.D., Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06890585
- Sponsor's protocol ID
- B2024-849-01
- Status last verified
- Mar 2025
- First submitted
- 17 Mar 2025
- Last updated
- 24 Mar 2025
- 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 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Open-Label Phase II Clinical Study Comparing the Efficacy and Safety of Zanubrutinib, Chidamide, and Rituximab Induction Therapy Sequentially Combined With or Without CHOP Versus R-CHOP in the First-Line Treatment of Patients With Newly Diagnosed Double-Expressor Diffuse Large B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT06890585
- Acronym / sponsor ID
- B2024-849-01
- Conditions
- BTK Inhibitors, Histone Deacetylase Inhibitor, Double Express Diffuse Large B-cell Lymphoma
- Keywords
- Double Expressor Diffuse Large B-cell Lymphoma, zanubrutinib, chidamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 128 participants (estimated)
- Lead sponsor
- Li ZhimingUniversity, hospital or other
- Study start
- 1 Jun 2025 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 24 Mar 2025 (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, as a new generation of BTK inhibitors, has shown more potent antitumor activity and lower adverse reactions than ibrutinib in head-to-head clinical studies, which make it a promising regimen for B cell lymphoma. Chidamide is an oral subtype-selective histone deacetylase inhibitor.
This Randomized, Multicenter, Open-Label Phase II Clinical Study is comparing the efficacy and safety of Zanubrutinib, Chidamide, and Rituximab induction therapy sequentially combined with or without CHOP versus R-CHOP in the first-line treatment of patients with newly diagnosed double-expressor DLBCL.
Detailed description
This study is designed to compare the efficacy and safety of zanubrutinib, chidamide, and rituximab (ZCR) induction therapy sequentially combined with or without CHOP regimen versus the standard R-CHOP regimen as first-line treatment for newly diagnosed double-expressor DLBCL. This study targets patients with MYC/BCL2 double-expressing DLBCL, a group with poor prognosis under traditional R-CHOP treatment.
The study consists of screening period, treatment period, and follow-up period, with subjects randomly assigned to the experimental group and the control group in a 1:1 ratio. The primary endpoint is the end-of-treatment complete response rate (EOT-CRR), while secondary endpoints include the overall response rate (EOT-ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A total of 128 patients are planned to be enrolled.
Efficacy evaluation will be conducted using the 2014 Lugano criteria, with imaging examinations such as PET-CT to objectively measure treatment response. adverse events (AEs) throughout the entire trial and grade the severity of adverse events will be recorded according to the guidelines of the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) 5.0.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZCR-CHOP | Experimental | Drug: ZCR-CHOPCycle 1-2 Drug: Zanubrutinib Zanubrutinib will be given at a dose of 160mg，bid，from d1 to d21 in a 21-day cycle Drug: Chidamide Chidamide will be given at a dose of 20 mg after breakfast on day 1, day 4, day 8, day 11 in a 21-day cycle Drug: Rituximab Rituximab will be given at a dose of 375 mg/m2 by IV on day 1 in a 21-day cycle Cycle 3-8 Patients who achieve complete response evaluated by PEC-CT per Lugano 2014 criteria after two course of treatment will continue to take Zanubrutinib, chidamide, and rituximab for up to 8 cycles in total. Patients who achieve partial response and stable disease will take ZCR combined with CHOP or up to 8 cycles in total. CHOP : cyclophosphamide 750 mg/m2 IV D1, Doxorubicin/Epirubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 IV [maximum total 2 mg], and prednisone 30 mg orally tid from d1 to d5 in a 21-day cycle |
| R-CHOP | Active comparator | Drug: R-CHOPR-CHOP Rituximab 375 mg/m2 IV on d1, cyclophosphamide 750 mg/m2 IV on d1, Doxorubicin/Epirubicin 50 mg/m2 IV on d1, vincristine 1.4 mg/m2 IV [maximum total 2 mg] on d1, and prednisone 30 mg orally tid from d1 to d5 in a 21-day cycle for up to 6 cycles. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Newly diagnosed MYC/BCL2 double-expressor DLBCL confirmed by pathological histology/clinical imaging, with IHC BCL2 expression ≥50% and MYC expression ≥40%.
- Male or female patients aged 18-65 years.
- ECOG score of 0-2.
- Expected survival time of ≥6 months.
- Must have at least one evaluable or measurable lesion according to the Lugano 2014 criteria [Evaluable lesion: lymph node or extranodal local uptake increased (higher than the liver) on 18F-Fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) scan, and PET and/or Computed Tomography (CT) features consistent with lymphoma; Measurable lesion: nodal lesion with a long diameter >15mm or extranodal lesion with a long diameter >10mm, with increased 18FDG uptake]. Patients with no measurable lesions and diffuse 18FDG uptake in the liver should be excluded.
Key exclusion criteria (21 listed)
- Special types of DLBCL:Fluid overload-associated large B-cell lymphoma, primary mediastinal large B-cell lymphoma, mediastinal gray zone lymphoma, primary central nervous system (CNS) DLBCL, double-hit DLBCL with BCL2 and MYC rearrangements.
- Transformed DLBCL (e.g., DLBCL transformed from follicular lymphoma, chronic lymphocytic leukemia/small B-cell lymphoma), secondary CNS involvement of DLBCL.
- History of other malignancies within the past 5 years, except for squamous cell carcinoma of the skin, basal cell carcinoma of the skin, and carcinoma in situ of the cervix.
- Major surgery within the past 2 months (excluding diagnostic surgery).
- Previous treatment for NHL, including chemotherapy, immunotherapy, radiotherapy, monoclonal antibody therapy, or surgical treatment (excluding diagnostic surgery and biopsy).
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 |
|---|---|---|
| ZCR-CHOPZanubrutinib, Chidamide, and Rituximab Induction Therapy Sequentially Combined With or Without CHOP | Drug | ZCR-CHOP |
| R-CHOPR-CHOP | Drug | R-CHOP |
Primary outcome
EOT-CR
Time frame: Approximately 12 months
defined as the proportion of subjects with measurable disease who achieve CR at the end of treatment according to 2014 Lugano criteria
5 secondary outcomes
EOT-ORR
Time frame: Approximately 12 months
Duration of response（DOR）
Time frame: Approximately 24 months
Progression-free survival (PFS)
Time frame: Approximately 24 months
Overall survival (OS)
Time frame: Approximately 24 months
Adverse Events (AE)
Time frame: Approximately 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- 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.
Zhiming Li, M.D. principal investigator
Sun Yat-Sen University Cancer Center
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 ZCR-CHOP and R-CHOP in people with BTK Inhibitors and Histone Deacetylase Inhibitor, run by Li Zhiming 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 9 inclusion and 21 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: opening soon, as of the sponsor's last update on 24 Mar 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhiming Li, M.D. (+86-020-87343292, lizhm@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EOT-CR (time frame: Approximately 12 months). 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 24 Mar 2025.