Aplastic AnemiaPhase 1TIARANCT05386264
Autologous Tregs for Aplastic Anaemia
A Phase 1 study testing Expanded autologous T regulatory cells in people with Aplastic Anemia, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- Expanded autologous T regulatory cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Jul 2022to 30 Apr 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
King's College Hospital
London
Shreyans Gandhi, shreyans.gandhi@nhs.net
Maclaine Hipolito, mhipolito@nhs.net
About this study
Official title: 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
Read the 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.
- Conditions
- Aplastic Anemia
- Being tested
- Expanded autologous T regulatory cells
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Expanded autologous T regulatory cellsOther
A 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15
| Study group | Role | What they receive |
|---|---|---|
| Expanded autologous T regulatory cells | Experimental | This is an open-label, non-randomised interventional trial. Receives: Other: Expanded autologous T regulatory cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: Baseline to 24 months post final infusion
Secondary outcomes (4)
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
Measured: Baseline to 24 months post final infusion
Overall survival
Survival status will be determined by the trial clinician at 6, 12 and 24 months
Measured: 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.
Measured: 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
Measured: Baseline to 24 months post final infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2022
- Study start14 Jul 2022
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label dose finding phase 1
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ghulam Mufti, Study director, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05386264
- Sponsor's protocol ID
- 2021-000082-33
- Acronym
- TIARA
- Status last verified
- Oct 2023
- First submitted
- 18 Feb 2022
- Last updated
- 5 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Matto N, Gandhi S, Rzepkowska M, Gerlevik S, Karimi MM, Kulasekararaj A, Douiri A, Miller A, Duran L, Cui H, Lewis J, Kordasti S, Lombardi G, Napolitani G, Mufti GJ. Phase I trial of autologous regulatory T cells for immune aplastic anemia. Haematologica. 2026 Sep 1;111(9):2966-2977. doi: 10.3324/haematol.2025.288962. Epub 2026 Feb 26.
PubMed 41742894
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Production of Expanded Autologous Regulatory T Cells to Treat Patients With Refractory Aplastic Anaemia in a Phase I Dose Finding Study
- ClinicalTrials.gov ID
- NCT05386264
- Acronym / sponsor ID
- TIARA / 2021-000082-33
- Conditions
- Aplastic Anemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Study start
- 14 Jul 2022 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 23 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label dose finding phase 1
| Arm | Type | Receives |
|---|---|---|
| Expanded autologous T regulatory cells | Experimental | Other: Expanded autologous T regulatory cellsThis is an open-label, non-randomised interventional trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Expanded autologous T regulatory cellsA 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15 | Other | Expanded autologous T regulatory cells |
Primary outcome
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
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
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
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
4 secondary outcomes
Response rate and duration of haematological response
Time frame: Baseline to 24 months post final infusion
Overall survival
Time frame: 6 months to 24 months post final infusion
Number and severity of infections
Time frame: Baseline to 24 months post final infusion
Clonal evolution to MDS/AML post treatment with Tregs
Time frame: Baseline to 24 months post final infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
- Derived from this study: PubMed 41742894Matto N, Gandhi S, Rzepkowska M, Gerlevik S, Karimi MM, Kulasekararaj A, Douiri A, Miller A, Duran L, Cui H, Lewis J, Kordasti S, Lombardi G, Napolitani G, Mufti GJ. Phase I trial of autologous regulatory T cells for immune aplastic anemia. Haematologica. 2026 Sep 1;111(9):2966-2977. doi: 10.3324/haematol.2025.288962. Epub 2026 Feb 26.
Related trials for Aplastic Anemia
RecruitingObservational study
Natural History of Acquired and Inherited Bone Marrow Failure Syndromes
Severe Aplastic Anemia, Telomere Biology Disorders
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
RecruitingObservational study
Mobilization of CD34+ Peripheral Blood Stem Cells in Patients With Diamond Blackfan Anemia Syndrome (DBAS)
Diamond Blackfan Anemia
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ghulam Mufti study director
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Expanded autologous T regulatory cells in people with Aplastic Anemia, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jen Lewis (07890254538, jen.lewis@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expandability of functional T-regulatory cells from AA patients (time frame: Manufacturing to 24 months post final infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05386264, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.