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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
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.
Details
| Lead sponsor | Cancer Research UK |
|---|---|
| Phase | Phase 1/Phase 2 |
| Status | RECRUITING |
| Enrolment | 84 |
| Start date | 2024-02-07 |
| Completion | 2029-12-21 |
Conditions
- Lymphoma, Non-Hodgkin
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Mantle-Cell
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Large B-cell Lymphoma
Interventions
- ALETA-001
Primary outcomes
- Dose level of ALETA-001 and timing of administration for use in Dose Expansion (Safety Lead-in Phase). — Day 1 to Day 28.
Determine a dose level that is deemed tolerable and timing of administration based on available safety and pharmacodynamic data. - Number of Participants who experience dose limiting toxicities (DLTs). — Up to Day 28.
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. - Number of Participants who experience Grade 3, 4 or 5 related adverse event (AEs). — 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.
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. - Best Overall Response (Dose Expansion Phase). — Radiological assessment from within 28 days before starting ALETA-001 and up to 12 months after.
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). - Progression-Free Survival (PFS) (Dose Expansion Phase). — From date of first dose of ALETA-001 up to 12 months.
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. - Time to Progression (TTP) (Dose Expansion Phase). — From date of first dose of ALETA-001 up to 12 months.
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.
Countries
United Kingdom