Drug intelligence / Profile preview

ibrutinib + rituximab + dexamethasone + cytarabine + cisplatin + oxaliplatin

Development stage
Discontinued
Lead developer
The Lymphoma Academic Research Organisation
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Oral, Intravenous
01

Overview

This combination therapy regimen consists of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and immunochemotherapy backbones R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) or R-DHAOx (rituximab, dexamethasone, cytarabine, and oxaliplatin). Developed and investigated by The Lymphoma Academic Research Organisation (LYSARC), this regimen was evaluated in a Phase Ib study for patients with various B-cell lymphomas, including relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Ibrutinib works by covalently and irreversibly inhibiting BTK, a key component of the B-cell receptor signaling pathway. Rituximab is a monoclonal antibody targeting CD20, while the chemotherapy components provide cytotoxic effects through DNA synthesis inhibition (cytarabine), DNA cross-linking (cisplatin/oxaliplatin), and anti-inflammatory/lympholytic activity (dexamethasone). Clinical results indicated significant hematological and infectious toxicities, leading to the inability to recommend a dose for Phase II development with the R-DHAP backbone.

Brand names
ImbruvicaRituxanMabThera
Other names
ibrutinib + R-DHAPibrutinib + R-DHAOxibrutinib + immunochemotherapies
02

Targets

DNA polymerase familyCD20 (B-lymphocyte antigen CD20)DNAGR (Glucocorticoid receptor)BTK (Bruton tyrosine kinase)

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