A Phase I/II Trial of ALETA-001 for the Treatment of Participants With B-cell Malignancies
A Cancer Research UK Phase I/II Trial of ALETA-001 in Participants Who Have Received an Anti-CD19 CAR T-Cell Therapy for the Treatment of B-cell Malignancies
2 other identifiers
interventional
84
1 country
7
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2024
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 15, 2023
CompletedFirst Posted
Study publicly available on registry
September 21, 2023
CompletedStudy Start
First participant enrolled
February 7, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 21, 2029
July 28, 2025
July 1, 2025
4 years
August 15, 2023
July 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (7)
Dose level of ALETA-001 and timing of administration for use in Dose Expansion (Safety Lead-in Phase).
Determine a dose level that is deemed tolerable and timing of administration based on available safety and pharmacodynamic data.
Day 1 to Day 28.
Number of Participants who experience dose limiting toxicities (DLTs).
DLTs will be assessed up to Day 28 and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the 28 days of the first dose of ALETA-001.
Up to Day 28.
Number of Participants who experience Grade 3, 4 or 5 related adverse event (AEs).
Related AEs are those considered by the investigator to be possibly, probably or highly probably related to ALETA-001. Events of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity (ICANS) are graded according to the American Society for Transplantation and Cellular Therapy grading criteria. All other AEs are graded according to the Common Terminology Criteria for AEs (CTCAE) Version 5.0.
Safety data will be collected from the time of informed consent until 95 days after the last dose of ALETA-001. The average time from consent to the end of follow up will be presented.
Best Overall Response (Dose Expansion Phase).
Best Overall Response according to Lugano criteria (Cheson, Journal of Clinical Oncology, 2014), the number of participants taking part in the Dose Expansion Phase with best overall response of complete response (CR), partial response (PR), no response or stable disease (SD/NR), and progressive disease (PD).
Radiological assessment from within 28 days before starting ALETA-001 and up to 12 months after.
Progression-Free Survival (PFS) (Dose Expansion Phase).
Median PFS measured from first dose of ALETA-001 to date of progression according to Lugano criteria or date of death without a previous progression recorded.
From date of first dose of ALETA-001 up to 12 months.
Time to Progression (TTP) (Dose Expansion Phase).
Median TTP measured from first dose of ALETA-001 to date of progression according to Lugano criteria. Participants who die without recorded progression will be censored.
From date of first dose of ALETA-001 up to 12 months.
Overall Survival (OS) (Dose Expansion Phase).
Median OS measured from first dose of ALETA-001 to date of death due to any cause or to the date of censoring at the last time the participant was known to be alive.
Follow-up until end of trial, estimated to be up to 48 months.
Secondary Outcomes (9)
Best Overall Response (Safety Lead-in Phase).
Radiological assessment from within 28 days before starting ALETA-001 and up to 12 months after.
Progression-Free Survival (PFS) (Safety Lead-in Phase).
From date of first dose of ALETA-001 up to 12 months.
Time to Progression (TTP) (Safety Lead-in Phase).
From date of first dose of ALETA-001 up to 12 months.
Overall Survival (OS) (Safety Lead-in Phase).
Follow-up until end of trial, estimated to be up to 48 months.
Maximum observed serum concentration (Cmax) of ALETA-001.
Day 1 to Day 7.
- +4 more secondary outcomes
Study Arms (2)
Safety Lead-In Phase
EXPERIMENTALDose Expansion Phase
EXPERIMENTALInterventions
ALETA-001 will be administered intravenously (IV) every two weeks.
Eligibility Criteria
You may qualify if:
- 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.
- +5 more criteria
You may not qualify if:
- 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):
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cancer Research UKlead
- Aleta BioTherapeuticscollaborator
Study Sites (7)
University Hospital Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Cambridge University Hospitals
Cambridge, United Kingdom
St James's University Hospital
Leeds, United Kingdom
University Hospital London Hospital
London, United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom
The Christie Hospital
Manchester, United Kingdom
Royal Marsden Hospital
Sutton, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sridhar Chaganti, Dr
University Hospital Birmingham NHS Foundation Trust
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 15, 2023
First Posted
September 21, 2023
Study Start
February 7, 2024
Primary Completion (Estimated)
February 1, 2028
Study Completion (Estimated)
December 21, 2029
Last Updated
July 28, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- All requests made within 5 years from the end of trial will be considered; requests made subsequently will be considered where possible.
- Access Criteria
- When a request has been approved, Cancer Research UK will provide access to the de-identified individual patient-level data and appropriate supporting information. A signed Data Sharing Agreement must be in place before accessing requested information. Requests should be submitted to drugdev@cancer.org.uk.
Individual de-identified patient data that underlie the results reported will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.