Autologous Tregs for Aplastic Anaemia (TIARA)

King's College Hospital NHS Trust

Status and phase

Enrolling

Phase 1

Conditions

Aplastic Anemia

Treatments

Other: Expanded autologous T regulatory cells

Study type

Interventional

Funder types

Other

Identifiers

NCT05386264

2021-000082-33

Details and patient eligibility

About

This Phase I study will determine the safety and optimal dose of expanded autologous Tregs to treat patients with Aplastic Anaemia (AA) (who have failed, or are considered ineligible for IST (immunosuppressive therapy) / other treatments) using expanded autologous T regulatory cells (Tregs) from AA patients at King's College Hospital, that have been prepared at the licensed Good Manufacturing Practices (GMP) production facility at Guy's Hospital, London

Full description

The clinical trial will examine the safety of giving AA patients who have failed other treatment(s), their own ('autologous') expanded Tregs - a form of 'cellular therapy - to treat the AA. The investigators 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. Expanded autologous Tregs are currently being looked at to treat other autoimmune disorders such as type I diabetes mellitus, multiple sclerosis, Crohn's disease and systemic lupus erythematosus. Results so far indicate that they are safe to give and do improve these diseases, but significantly this will be the first trial in AA.

Enrollment

12 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Acquired idiopathic AA
No evidence of constitutional/inherited AA based on clinical findings, absence of family history of AA, normal DEB test and normal Kings bone marrow failure gene panel
Very severe, severe or non-severe AA
Lack a matched sibling donor (MSD) or matched unrelated donor (MUD), or ineligible for MSD/MUD HSCT
Transfusion dependent
Failed or ineligible for a course of ATG and CSA
Failed / intolerant or inappropriate to treat with Eltrombopag or fails to meet Blueteq approval for use of Eltrombopag using NHS England guidance
AST < 3 x upper limit of normal (ULN), bilirubin < 1.5 x ULN (unless Gilbert's syndrome)
eGFR >50mL/min
Age ≥ 18 years, male or female
Willing and able to provide written and informed consent
If female of child-bearing potential, have a negative serum pregnancy test and agree to use adequate contraceptive methods if of reproductive age
Diffusing capacity for carbon monoxide (DLCO) ≥ 45% predicted corrected for haemoglobin
LVEF > 40%.
Performance status ≤ 2

Exclusion criteria

Constitutional AA
Age < 18 years' old
Have a MSD and are eligible for MSD HSCT
Have a MUD and are eligible for MUD HSCT
Hypocellular myelodysplastic syndrome (Hypo MDS) or AA/Hypo MDS overlap
Uncontrolled ongoing infection
Active malignancy
Treatment of cancer in the last 5 years (except in situ carcinoma of the cervix or basal cell carcinoma)
Unable to give informed consent
Active or uncontrolled infection not responding to appropriate antibiotics and antifungal agents.
Human immunodeficiency virus (HIV) sero-positivity, hepatitis B, hepatitis C or hepatitis E infection.
Abnormal organ function: AST/ALT >3 x upper limit of normal (ULN), bilirubin >1.5 x ULN, eGFR ≤50mL/min
Heart failure (= grade III New York Heart Association)
Pregnant or lactating women
Unable or unwilling to comply with the contraceptive requirements