autologous tregs for aplastic anaemia

Conditions: Aplastic Anemia

Summary: 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

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.

Eligibility criteria:
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