- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05386264
Autologous Tregs for Aplastic Anaemia (TIARA)
October 4, 2023 updated by: King's College Hospital NHS Trust
Production of Expanded Autologous Regulatory T Cells to Treat Patients With Refractory Aplastic Anaemia in a Phase I Dose Finding Study
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
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Estimated)
12
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Jen Lewis
- Phone Number: 07890254538
- Email: jen.lewis@kcl.ac.uk
Study Locations
-
-
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London, United Kingdom
- Recruiting
- King's College Hospital
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Contact:
- Shreyans Gandhi
- Email: shreyans.gandhi@nhs.net
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Contact:
- Maclaine Hipolito
- Email: mhipolito@nhs.net
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Principal Investigator:
- Shreyans Gandhi
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Expanded autologous T regulatory cells
This is an open-label, non-randomised interventional trial.
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A 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Expandability of functional T-regulatory cells from AA patients
Time Frame: 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
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Manufacturing to 24 months post final infusion
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Assessment of safety and toxicity profile of the administrated autologous T-regulatory cells in AA patients
Time Frame: Baseline to 24 months post final infusion
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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
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Baseline to 24 months post final infusion
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Evaluation of safety and toxicity profile following 2 doses of autologous T-regulatory cells in AA patients
Time Frame: 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
|
Baseline to 24 months post final infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate and duration of haematological response
Time Frame: Baseline to 24 months post final infusion
|
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
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Baseline to 24 months post final infusion
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Overall survival
Time Frame: 6 months to 24 months post final infusion
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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
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Number and severity of infections
Time Frame: Baseline to 24 months post final infusion
|
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.
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Baseline to 24 months post final infusion
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Clonal evolution to MDS/AML post treatment with Tregs
Time Frame: Baseline to 24 months post final infusion
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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
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Baseline to 24 months post final infusion
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Ghulam Mufti, King's College London
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 14, 2022
Primary Completion (Estimated)
September 30, 2024
Study Completion (Estimated)
April 30, 2025
Study Registration Dates
First Submitted
February 18, 2022
First Submitted That Met QC Criteria
May 18, 2022
First Posted (Actual)
May 23, 2022
Study Record Updates
Last Update Posted (Actual)
October 5, 2023
Last Update Submitted That Met QC Criteria
October 4, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2021-000082-33
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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