A Phase I/II Trial of ALETA-001 for the Treatment of Participants With B-cell Malignancies

NCT ID: NCT06045910

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-07
• Study Completion Date: 2029-12-21

Brief Summary

This is a Phase I/II multicentre, open-label trial designed to evaluate the efficacy, safety, tolerability, timing of administration and pharmacokinetics (PK) of a novel chimeric antigen receptor (CAR) T-cell engager, ALETA-001, administered by intravenous (IV) infusion as a single agent every 2 weeks in participants with B-cell malignancies post CD19 CAR T-cell therapy. This first in human study is divided into 2 parts: a safety lead-in phase (Phase I) and a dose expansion phase (Phase II). Different dose levels of ALETA-001 and timing of administration will be evaluated in Phase I in order to define a recommended dosing level and time of administration for Phase II. Phase II will further evaluate the safety, PK and therapeutic activity of ALETA-001.

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, B-Cell; Large B-cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Safety Lead-In Phase

Group Type: EXPERIMENTAL

ALETA-001

Intervention Type: DRUG

ALETA-001 will be administered intravenously (IV) every two weeks.

Dose Expansion Phase

Group Type: EXPERIMENTAL

ALETA-001

Intervention Type: DRUG

ALETA-001 will be administered intravenously (IV) every two weeks.

Interventions

ALETA-001

ALETA-001 will be administered intravenously (IV) every two weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

For all participants

Criteria to be met prior to enrolment in the trial:

• Aged 16 years or over.
• Written (signed and dated) informed consent and be capable of co-operating with ALETA-001 administration and follow-up.
• Confirmed diagnosis of B-cell NHL according to World Health Organization (WHO) 2016 criteria.
• Eastern Cooperative Oncology Group performance status of 0, 1 or 2.
• Biochemical indices within protocol specified ranges.

• Histologically confirmed diagnosis of relapsed/refractory LBCL or MCL.
• Have received an approved anti-CD19 CAR T-cell therapy.
• Objectively evaluable or measurable disease at 4 weeks (±1 week) post CAR T, which demonstrates:

• inadequate or incomplete response (PR or SD), or
• PD if there is a reasonable expectation of deriving benefit from trial treatment, or
• initial response followed by relapse within 9 months assessed according to Lugano Criteria.
• Haematological indices within protocol specified ranges.

• Histologically confirmed diagnosis of relapsed/refractory LBCL or MCL.
• Approved by the UK national CAR T Clinical Panel (NCCP) to receive an approved anti-CD19 CAR T-cell therapy.
• Haematological indices within protocol specified ranges.
• Adequate cardiac function within protocol specified ranges with no clinical symptoms or signs of heart failure.
• Resting O2 saturation of ≥92% on room air.

Eligibility for participants in Phase II of the trial will depend on timing of administration of ALETA-001 which will be recommended by the Safety Review Committee (SRC).

Exclusion Criteria

• Active or previous malignancies of other types that, in the opinion of the Investigator, should exclude the participant. Exceptions include adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and patients with asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or who require only hormonal therapy and have had normal prostate specific antigen for >1 year prior to the start of therapy. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 2 years or more and are deemed at negligible risk for recurrence, are eligible for the trial.
• Any ongoing toxic manifestation of previous anti-cancer treatment that, in the opinion of the Investigator, should exclude the participant.
• Ongoing need for systemic immunosuppressive therapy other than replacement dose of corticosteroids. Intermittent topical, inhaled or intranasal corticosteroids are permitted.
• Presence of active infections and/ or inflammatory disease requiring active management.
• Documented current central nervous system involvement by lymphoma.
• Women of childbearing potential (or are already pregnant or lactating) unless willing to adhere to protocol-defined contraceptive requirements.
• Male patients with partners of childbearing potential unless willing to adhere to protocol-defined contraceptive requirements.
• Major thoracic or abdominal surgery from which the participant has not yet recovered.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• Hypersensitivity to any of the ingredients/excipients in ALETA-001.
• Participation in another interventional clinical trial, whilst taking part in this trial of ALETA-001. Participation in an observational trial or interventional clinical trial that does not involve administration of an IMP and that would not place an unacceptable burden on the participant, in the opinion of the Investigator and CDD, would be acceptable.
• Participants with any congenital or acquired immunodeficiency syndrome or who are receiving immunosuppressive therapy (including any dose of systemic corticosteroids), or who are immunosuppressed post organ transplant. However, participants receiving inhaled corticosteroids and participants with a history of allergy (other than anaphylaxis) are eligible, as are participants with a history of autoimmune disease.
• Any other condition that, in the Investigator's opinion, would mean that the trial is not in the best interests of the participant.
• Concurrent radiotherapy (except for palliative reasons).

Cohorts A & B):

• Participants who have received any other systemic anti-cancer treatment post-CAR T.
• Potential participants who experienced any of the following because of the initial CAR T treatment:

• Grade 4 CRS or ICANS post CAR T infusion.
• Grade ≥3 CRS or ICANS persisting beyond 7 days despite optimal therapy.
• Any Grade ≥1 CRS or ICANS must have fully resolved.
• Any Grade ≥3 organ toxicity (other than haematologic toxicity) following CAR T infusion must have improved to Grade ≤2 for at least 48 hours prior to ALETA-001 infusion.

• Grade 4 CRS or ICANS post CAR T infusion.
• Grade ≥3 CRS or ICANS persisting beyond 7 days despite optimal therapy.
• Any Grade ≥2 CRS or ICANS must have improved to Grade ≤1 for at least 48 hours prior to ALETA-001 infusion.
• ECOG performance status ≥3.
• Any Grade ≥3 organ toxicity (other than haematologic toxicity) following CAR T infusion must have improved to Grade ≤2 for at least 48 hours prior to ALETA-001 infusion.
• Any unresolved serious active infection which in the opinion of the Investigator precludes ALETA-001 infusion (ongoing need for IV antimicrobial therapy per se is not an exclusion).

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aleta BioTherapeutics

UNKNOWN

Sponsor Role: collaborator

Cancer Research UK

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sridhar Chaganti, Dr

Role: PRINCIPAL_INVESTIGATOR

University Hospital Birmingham NHS Foundation Trust

Locations

University Hospital Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status: RECRUITING

Cambridge University Hospitals

Cambridge, , United Kingdom

Site Status: RECRUITING

St James's University Hospital

Leeds, , United Kingdom

Site Status: RECRUITING

University Hospital London Hospital

London, , United Kingdom

Site Status: RECRUITING

Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status: RECRUITING

The Christie Hospital

Manchester, , United Kingdom

Site Status: RECRUITING

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status: NOT_YET_RECRUITING

Countries

United Kingdom

Central Contacts

Alka Lal

Role: CONTACT

aleta@cancer.org.uk

+442034696034

Facility Contacts

Sridhar Chaganti, Dr

Role: primary

sridhar.chaganti@uhb.nhs.uk

01213714379

Ben Uttenthal, Dr

Role: primary

b.uttenthal@nhs.net

01223 586928

Mary Owen, Dr

Role: primary

mary.owen1@nhs.net

01132068577

William Townsend, Dr

Role: primary

william.townsend@nhs.net

0203 447 9443

Jane Norman, Dr

Role: primary

Jane.norman@mft.nhs.uk

01612764178, 01612768686

Adam Gibb, Dr

Role: primary

adam.gibb@nhs.net

0161 446 3753

Sunil Iyengar, Dr

Role: primary

sunil.iyengar@rmh.nhs.uk

02078082609

Other Identifiers

IRAS ID: 1007028

Identifier Type: OTHER

Identifier Source: secondary_id

CRUKD/23/001

Identifier Type: -

Identifier Source: org_study_id