Safety and Activity of SNX-5422 Plus Ibrutinib in CLL

Cancer Clinical Trial

Official title: A Phase 1, Open-label Study of SNX‑5422 and Ibrutinib in Chronic Lymphocytic Leukemia Subjects With a Mutation in Bruton's Tyrosine Kinase

Status Withdrawn

Clinical Trial Summary

SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will result in the removal of mutated BTK from blood mononuclear cells and/or prevents or delays disease progression of subjects with CLL

Clinical Trial Description

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation.

BTK is a critical kinase in the B cell receptor signaling pathway. This pathway is amplified in CLL and results in amplification of proliferation and anti-apoptotic signals. By inhibiting BTK, ibrutinib eliminates the activation of these pro-survival pathways and microenvironment survival signals. While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, which both decrease ibrutinib's affinity for BTK, and also changes the binding from irreversible to reversible. This is a proof of concept study to investigate whether the addition of SNX-5422 to an established dose of ibrutinib will reduce mutated BTK from CLL cells and/or prevents or delays disease progression of subjects with CLL.

This is an open-label study of SNX‑5422 combined with ibrutinib. In each 28 day cycle, SNX‑5422 will be dosed in the morning once every other day for 21 days, followed by a 7‑day drug‑free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon every day for 28 days. cycle ;

Related Conditions & MeSH terms

• Cancer

• NCT number: NCT02914327
• Study type: Interventional
• Source: Esanex Inc.
• Status: Withdrawn
• Phase: Phase 1
• Start date: February 2, 2017
• Completion date: July 1, 2018