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.
∙ 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.
∙ Cohort Specific Inclusion criteria (for Phase I Cohorts A \& B) Criteria to be met prior to enrolment in the trial.
• 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.
∙ Cohort Specific Inclusion criteria (for Phase I Cohorts C \& D) Criteria to be met prior to lymphodepleting chemotherapy for CAR T therapy.
• 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).