Production of Expanded Autologous Regulatory T Cells to Treat Patients With Refractory Aplastic Anaemia in a Phase I Dose Finding Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Expandability of functional T-regulatory cells from AA patients
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Expandability of functional T-regulatory cells from AA patients
时间窗: Manufacturing to 24 months post final infusion
This will be assessed through measuring the T regulatory cell count (1) during manufacturing production using a NC-200 cell counter and (2) through FACS analysis on peripheral blood research samples collected at the following 7 time points: pre-dose day 1, days 15, 29, 58 and at 6, 12 and 24 months
Assessment of safety and toxicity profile of the administrated autologous T-regulatory cells in AA patients
时间窗: Baseline to 24 months post final infusion
This will be assessed through physical examinations prior to each infusion and at every follow up visit. ECOG assessments prior to each infusions and at 6, 12 and 24 months. Bloods tests (FBC, Biochemistry, coagulation screen, d-dimer) prior to each infusion as well as 1 hour after infusion and 6 hours after the end of infusion). Bone marrow assessment prior to initial infusion and at 6, 12 and 24 months. AEs, SARs and SUSARs will be monitored from date of informed consent until 24 months. SAEs will be monitoring from date of informed consent until 30 days post final infusion. Adverse Events will be graded using CTCAE Version 5.0
Evaluation of safety and toxicity profile following 2 doses of autologous T-regulatory cells in AA patients
时间窗: Baseline to 24 months post final infusion
This will be assessed through physical examinations prior to each infusion and at every follow up visit. ECOG assessments prior to each infusions and at 6, 12 and 24 months. Bloods tests (FBC, Biochemistry, coagulation screen, d-dimer) prior to each infusion as well as 1 hour after infusion and 6 hours after the end of infusion). Bone marrow assessment prior to initial infusion and at 6, 12 and 24 months. AEs, SARs and SUSARs will be monitored from date of informed consent until 24 months. SAEs will be monitoring from date of informed consent until 30 days post final infusion. Adverse Events will be graded using CTCAE Version 5.0
次要结局
- Overall survival(6 months to 24 months post final infusion)
- Response rate and duration of haematological response(Baseline to 24 months post final infusion)
- Clonal evolution to MDS/AML post treatment with Tregs(Baseline to 24 months post final infusion)
- Number and severity of infections(Baseline to 24 months post final infusion)