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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Expanded autologous T regulatory cells | Experimental | This is an open-label, non-randomised interventional trial. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Expanded autologous T regulatory cells | Other | A 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Expandability of functional T-regulatory cells from AA patients | 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 | Manufacturing to 24 months post final infusion |
| Assessment of safety and toxicity profile of the administrated autologous T-regulatory cells in AA patients | 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 | Baseline to 24 months post final infusion |
| Evaluation of safety and toxicity profile following 2 doses of autologous T-regulatory cells in AA patients | 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 | Baseline to 24 months post final infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Response rate and duration of haematological response | This will be assessed by examining serial full blood counts, transfusion requirements and IV antibiotic usage on days D1, D2 D8, D15, D22, D29 and at 6, 12 and 24 months | Baseline to 24 months post final infusion |
| Overall survival |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jen Lewis | Contact | 07890254538 | jen.lewis@kcl.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Ghulam Mufti | King's College London | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| King's College Hospital | Recruiting | London | United Kingdom |
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| ID | Term |
|---|---|
| D000741 | Anemia, Aplastic |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000080983 | Bone Marrow Failure Disorders |
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Open-label dose finding phase 1
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Survival status will be determined by the trial clinician at 6, 12 and 24 months |
| 6 months to 24 months post final infusion |
| Number and severity of infections | The number and severity of infections during first 30 days prior to starting Tregs will be compared to monthly average during therapy with Tregs until 24 months. This will be assessed through clinical examination and results of infection screening tests as recorded on EPR (Electronic Patient Records). Severity infections will be classified using the NCI Common Terminology Criteria for Adverse Events (CTCAE) for recording AEs and grade. | Baseline to 24 months post final infusion |
| Clonal evolution to MDS/AML post treatment with Tregs | This will be assessed through (a) BM morphology (b) SNP-A karyotyping and (c) mutational profile, using Kings myeloid gene panel that includes 44 myeloid specific genes, at baseline (screening), 6, 12 and 24 months | Baseline to 24 months post final infusion |
| D001855 | Bone Marrow Diseases |