TIARA
Research type
Research Study
Full title
Production of expanded autologous regulatory T cells to treat patients with aplastic anaemia: A phase I study
IRAS ID
294362
Contact name
Ghulam Mufti
Contact email
Sponsor organisation
King’s College London
Eudract number
2021-000082-33
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 4 months, 31 days
Research summary
‘TIARA’ is a phase I clinical trial investigating the safety and tolerability of expanded autologous T regulatory cells (Tregs) to treat patients with Aplastic Anaemia (AA) who have failed, or are considered ineligible for IST / other treatments. Tregs (starting material) will be collected via a leukapheresis procedure at King’s College Hospital and manufactured in the GMP production facility at Guy’s Hospital. Two dose levels will be explored in a 3+3 dose escalation design. Expanded autologous Tregs are currently being looked at to treat other autoimmune disorders and results so far indicate that they are safe to give and do improve these diseases, but significantly, this will be the first trial globally in AA.
There are currently only two standard first-line treatments for AA: immune-suppressive therapy (IST), which uses drugs (antithymocyte globulin (ATG) and ciclosporin) that dampen down abnormal immune responses but only work in 2/3 AA patients, or stem cell transplantation, the only known curative AA treatment to date, but suitable only for a proportion of patients.
Our research has shown that Tregs are reduced in patients with AA. Recently, our team has used new technology, including high-resolution fluorescence cell sorting and CyTOF, that have provided us with fine detail about the type of immune cells that are present in AA. We can now clearly separate AA Tregs from normal Tregs, and we have gone on to successfully expand AA patients’ Tregs from their blood in the laboratory and show that they work normally at preventing the immune system attacking the bone marrow stem cells.
This clinical trial will examine the safety of giving AA patients their own autologous expanded Tregs, as a form of cellular therapy, to treat the AA. We will study the changes in the immune system and determine if healthy bone marrow stem cells recover, thereby improving the blood counts after giving Tregs to patients.
REC name
North East - York Research Ethics Committee
REC reference
22/NE/0021
Date of REC Opinion
29 Mar 2022
REC opinion
Further Information Favourable Opinion