Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients

Official Title

A Phase II Trial of Tisagenlecleucel in First-line High-risk (HR) Pediatric and Young Adult Patients With B-cell Acute Lymphoblastic Leukemia (B-ALL) Who Are Minimal Residual Disease (MRD) Positive at the End of Consolidation (EOC) Therapy

Summary:

This is a single arm, open-label, multi-centre, phase II study to determine the efficacy and safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who received first-line treatment and are EOC MRD positive. The study will have the following sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After tisagenlecleucel infusion, patient will have assessments performed more frequently in the first month and then at Day 29, then every 3 months for the first year, every 6 months for the second year, then yearly until the end of the study. Efficacy and safety will be assessed at study visits and as clinically indicated throughout the study. The study is expected to end in approximately 8 years after first patient first treatment (FPFT). A post-study long term follow-up for lentiviral vector safety will continue under a separate protocol per health authority guidelines.

Trial Description

Primary Outcome:

• Disease Free Survival (DFS) rate

• Percentage of participants who are disease free without allogeneic stem cell transplant (SCT)
• Overall Survival
• Percentage of participants achieving MRD negative CR or CRi at Month 3
• Percentage of participants with in CR or CRi with persistent B-cell aplasia over time post tisagenlecleucel infusion
• Percentage of participants who have tisagenlecleucel product successfully manufactured over the total number of subjects enrolled for the age ≥1 year and < 3 years
• Pediatric Quality of Life (PedsQL)
• European Quality of Life 5 dimensions (EQ-5D-3L & EQ-5D-Y))
• Impact of tisagenlecleucel on cognitive functioning using Computerized neurocognitive assessment: Detection test
• Impact of tisagenlecleucel on cognitive functioning usingComputerized neurocognitive assessment: Identification test
• Impact of tisagenlecleucel on cognitive functioning using Computerized neurocognitive assessment: Groton Maze Learning test
• Impact of tisagenlecleucel on cognitive functioning using Computerized neurocognitive assessment: One Back test
• Impact of tisagenlecleucel on cognitive functioning usingComputerized neurocognitive assessment: One card learning test
• Percentage of participants with pre-existing antibodies
• Percentage of participants with anti-m CAR19 antibodies post infusion with tisagenlecleucel and % of patients without measureable anti-mCAR19 antibodies
• Percentage of patients that have measureable anti-mCAR19 antibodies above patient specific cut-point (reported as a %) pre and post tisagenlecleucel infusion categorized by Day 28 response
• tisagenlecleucel transgene concentration
• Expression of tisagenlecleucel
• Persistence of CAR (reported as copies/ug) categorized by the time to B-cell recovery (recovery < 3 months, >3 months to < 6months, > 6 months)
• Cmax; cellular kinetic parameter of tisagenlecleucel
• Tmax; cellular kinetic parameter of tisagenlecleucel
• AUC0-29d and 84d; cellular kinetic parameter of tisagenlecleucel
• AUC0-Tmax; cellular kinetic parameter of tisagenlecleucel
• T1/2; cellular kinetic parameter of tisagenlecleucel
• Clast; cellular kinetic parameter of tisagenlecleucel
• Tlast; cellular kinetic parameter of tisagenlecleucel
• Impact of tisagenlecleucel dose on day 29 response
• AUC 0 - 29d; cellular kinetic parameter of tisagenlecleucel
• Cmax: cellular kinetic parameter of tisagenlecleucel
• Tmax: cellular kinetic parameter of tisagenlecleucel
• T1/2: cellular kinetic parameter of tisagenlecleucel

View this trial on ClinicalTrials.gov