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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Expanded autologous T regulatory cells
This is an open-label, non-randomised interventional trial.
Other: Expanded autologous T regulatory cells
A 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Manufacturing to 24 months post final infusion
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
Baseline to 24 months post final infusion
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
Baseline to 24 months post final infusion
Overall survival
Time Frame: 6 months to 24 months post final infusion
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
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.
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
King's College Hospital NHS Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 14, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 5, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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