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Clinical 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 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).


Clinical Trial 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


Related Conditions & MeSH terms


NCT number NCT05189197
Study type Interventional
Source Fudan University
Contact Junning Cao
Phone +86-18017312174
Email [email protected]
Status Not yet recruiting
Phase Phase 2
Start date January 2022
Completion date January 2026

See also
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