Autologous Tregs for Aplastic Anaemia

NCT ID: NCT05386264

Last Updated: 2023-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-14

Study Completion Date

2025-04-30

Brief Summary

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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

Detailed Description

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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

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Aplastic Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Open-label dose finding phase 1
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Expanded autologous T regulatory cells

This is an open-label, non-randomised interventional trial.

Group Type EXPERIMENTAL

Expanded autologous T regulatory cells

Intervention Type OTHER

A 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15

Interventions

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Expanded autologous T regulatory cells

A 3+3 dose escalation design with expanded T regulatory cells administered on Day 1 and Day 15

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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King's College Hospital NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ghulam Mufti

Role: STUDY_DIRECTOR

King's College London

Locations

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King's College Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Jen Lewis

Role: CONTACT

07890254538

Facility Contacts

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Shreyans Gandhi

Role: primary

Maclaine Hipolito

Role: backup

Other Identifiers

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2021-000082-33

Identifier Type: -

Identifier Source: org_study_id

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