Zanubrutinib, Chidamide, and Rituximab Induction With or Without CHOP Versus R-CHOP in Newly Diagnosed Double-Expressor DLBCL

NCT06890585 | Not Yet Recruiting Phase 2

• 1 other identifier: B2024-849-01
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

BTK Inhibitors; Histone Deacetylase Inhibitor; Double Express Diffuse Large B-cell Lymphoma

Keywords

Double Expressor Diffuse Large B-cell Lymphoma; zanubrutinib; chidamide

Outcome Measures

Primary Outcomes (1)

• EOT-CR

  defined as the proportion of subjects with measurable disease who achieve CR at the end of treatment according to 2014 Lugano criteria

  Approximately 12 months

Secondary Outcomes (5)

• EOT-ORR

  Approximately 12 months

• Duration of response（DOR）

  Approximately 24 months

• Progression-free survival (PFS)

  Approximately 24 months

• Overall survival (OS)

  Approximately 24 months

• Adverse Events (AE)

  Approximately 12 months

Other Outcomes (1)

• The consistency between ctDNA clearance and radiographic disease response

  Approximately 12 months

Study Arms (2)

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

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.

Drug: R-CHOP

Interventions

ZCR-CHOP DRUG

Zanubrutinib, Chidamide, and Rituximab Induction Therapy Sequentially Combined With or Without CHOP

ZCR-CHOP

R-CHOP DRUG

R-CHOP

R-CHOP

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Li Zhiming: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

R-CHOP protocol

Study Officials

• Zhiming Li, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiming Li, M.D.

CONTACT

+86-020-87343292; lizhm@sysucc.org.cn

Peng Sun, M.D.

CONTACT

+86-020-87343292; sunp@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: March 24, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)