NCT00820508

Safety and Tolerability of CHR-2845 to Treat Haematological Diseases or Lymphoid Malignancies

A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-2845, in Patients With Advanced or Treatment Refractory Haematological Diseases or Lymphoid Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Chroma Therapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether the histone deacetylase inhibitor CHR-2845 is tolerated in patients with haematological diseases and lymphoid malignancies.

Detailed description

CHR-2845 is a novel type of histone deacetylase inhibitor (HDACi) for use in cancer that, in addition to having broad ranging anti-proliferative activity against transformed cells, is designed to have an increased therapeutic window against diseases which involve cells of the monocyte-macrophage lineage. There are several HDACi's in clinical development and one, SAHA (Vorinostat, Zolinza®), has recently been approved for use in the treatment of cutaneous T-cell lymphoma. CHR-2845 is a cell-permeant ester that is metabolised to give an active acid, CHR-2847, which selectively accumulates in monocytes and macrophages. This results in a 20-100 fold increase in anti-proliferative potency of CHR-2845 for monocytic over non-monocytic tumour cells. This selectivity should lead to an increased therapeutic window in haematological malignancies involving cells of the monocyte lineage (AML M4, AML M5 and CMML). In addition, there is increasing evidence that monocytes and macrophages associated with some haematological tumours (tumour-associated macrophages (TAMs)) are involved in supporting the growth and spread of the tumour. This clinical trial will focus on haematological and lymphoid malignancies with the intention of evaluating the safety and tolerability of CHR-2845. Additionally it will compare response in patients where monocytes/macrophages are important disease drivers, with the response in other patients. This will allow an early determination of the potential improvement in therapeutic window afforded by the monocyte/macrophage directed HDACi activity.

Conditions

• Hematological Disease
• Lymphoid Malignancies

Interventions

Type	Name	Description
DRUG	CHR-2845	Once daily oral ingestion of capsules (10, 40 or 80mg), dose depending on cohort, treatment cycle of 28 days

Timeline

• Start date: 2008-12-01
• Primary completion: 2011-07-01
• Completion: 2011-07-01
• First posted: 2009-01-12
• Last updated: 2011-11-28

Locations

4 sites across 3 countries: Belgium, France, Netherlands