A Study to Evaluate Efficacy and Safety of Zanubrutinib With R-CHOP in Newly Diagnosed Non-GCB DLBCL Patients With Double Expression

  • STATUS
    Recruiting
  • End date
    Jan 14, 2026
  • participants needed
    41
  • sponsor
    Fudan University
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Updated on 14 March 2022
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Accepts healthy volunteers

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 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）.

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.

Details
Condition Diffuse Large B-cell Lymphoma(DLBCL)
Treatment Zanubrutinib + R-CHOP
Clinical Study IdentifierNCT05189197
SponsorFudan University
Last Modified on14 March 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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
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