BET116183: GSK525762 in Subjects with Haematologic Malignancies
Research type
Research Study
Full title
BET116183: A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with relapsed refractory haematologic malignancies
IRAS ID
137095
Contact name
Brian Huntly
Contact email
Sponsor organisation
GlaxoSmithKline
Eudract number
2013-000445-39
ISRCTN Number
n/a
Clinicaltrials.gov Identifier
n/a
Research summary
Haematological malignancies are cancers that affect the cells of the blood and include leukaemia, lymphoma and myeloma. They are often highly aggressive and are unfortunately fatal in the majority of cases. Although some effective therapies exist, identification of novel therapeutic targets and of agents effective against these targets are required to significantly improve outcomes in patients who do not respond to other treatment options.
A family of proteins, known as the Bromodomain and extra terminal or BET proteins, have been shown to regulate the expression of a number of genes that are critical for the maintenance of haematological malignancies. GSK has engineered a drug (GSK525762) that inhibits the function of these proteins, and switches off the expression of critical cancer-related genes. In extensive pre-clinical testing, the drugs have demonstrated highly promising results, leading to cell death and growth arrest in a number of models of haematological malignancy.
This trial will test the effectiveness of one of these inhibitors, GSK525762, in patients with relapsed haematological malignancies for whom no other effective treatment is available. Up to approximately 30 patients from the UK and from the US will take part in Part 1 of the study. For part 2 of the study, additional countries may join and up to approximately 40 people will participate. The primary aim of the study is to demonstrate that GSK525762 can be safely administered to patients with haematological malignancies and secondary aims are to determine the optimal dose of the drug and to assess its effectiveness against leukaemia, lymphoma and myeloma. Eligible patients will receive the drug orally and will be extensively monitored to ensure patient safety and assess the side effects of the drug and their management. Patients will also be monitored to assess the drugs effect on the tumour. Only when we are satisfied that unacceptable side effects are minimal, will dose escalation occur, both in existing and newly entered patients. When an optimal dose has been identified, a larger number of patients will be treated at this level to determine effects on disease. Proving that GSK525762 is safe and effective in relapsed haematological malignancies would provide another valuable agent to improve outcomes in these aggressive cancers.REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
13/EE/0429
Date of REC Opinion
20 Dec 2013
REC opinion
Favourable Opinion