Autologous Tregs for Aplastic Anaemia

NCT05386264 | Unknown Phase 1 DMC

• 1 other identifier: 2021-000082-33
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 College Hospital, that have been prepared at the licensed Good Manufacturing Practices (GMP) production facility at Guy's Hospital, London

Conditions

Aplastic Anemia

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (4)

• Response rate and duration of haematological response

  Baseline to 24 months post final infusion

• Overall survival

  6 months to 24 months post final infusion

• Number and severity of infections

  Baseline to 24 months post final infusion

• Clonal evolution to MDS/AML post treatment with Tregs

  Baseline to 24 months post final infusion

Study Arms (1)

Expanded autologous T regulatory cells

EXPERIMENTAL

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

Other: Expanded autologous T regulatory cells

Interventions

Expanded autologous T regulatory cells OTHER

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

Expanded autologous T regulatory cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (1)

King's College Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Ghulam Mufti

  King's College London

  STUDY DIRECTOR

Central Study Contacts

Jen Lewis

CONTACT

07890254538; jen.lewis@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label dose finding phase 1

Study Record Dates

• First Submitted: February 18, 2022
• First Posted: May 23, 2022
• Study Start: July 14, 2022
• Primary Completion: September 30, 2024
• Study Completion: April 30, 2025
• Last Updated: October 5, 2023

Record last verified: 2023-10

Locations

GB (1)