This study will evaluate the safety and tolerability of administering a novel bispecific CD19/CD22-directed CAR T cell product (CD19x22) for the treatment of relapsed or refractory pediatric B-ALL.
This is an open-label Phase I trial consisting of 2 cohorts to determine the safety and tolerability of CD19x22 CAR T in Pediatric Patients with R/R B-ALL. This trial will include two parallel cohorts based on disease burden prior to lymphodepleting chemotherapy, Cohort 1: high disease burden cohort: defined as \>=25% bone marrow lymphoblasts and/or non-CNS extramedullary disease, and Cohort 2: low disease burden cohort: defined as \<25% bone marrow lymphoblasts and no non-CNS extramedullary disease. Dose escalation will proceed independently within each cohort using the Bayesian Optimal Interval (BOIN) design. This trial will enroll up to 53 patients with 21 patients in each cohort receiving treatment with lymphodepleting chemotherapy followed by CD19x22 CAR T cell infusion, with a total of up to 42 treated patients overall. Patients will be assessed for dose limiting toxicities (up to 28 days from infusion) to determine a maximum tolerated dose (MTD) and for preliminary efficacy through morphological remission rate and measurable residual disease (MRD) levels.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
The investigational product is an autologous, genetically modified CD19xCD22 CAR T cell product produced by the Gates Biomanufacturing Facility.
Children's Hospital Colorado
Aurora, Colorado, United States
RECRUITINGSafety Measured by Dose Limiting Toxicities (DLTs)
The safety of the administering this bispecific CD19/CD22-directed CAR T cell product will be measured by assessing the DLTs in each disease burden cohort in a Bayesian optimal interval (BOIN) design to determine the MTD
Time frame: Infusion date to 28 days post-infusion
Overall Response Rate
The efficacy of this bispecific CD19/CD22-directed CAR T cell product will be measured by evaluating the overall response rate in each disease burden stratum based on a morphologic disease assessment to measure bone marrow status at Day 28 post-infusion.
Time frame: 28 days post-infusion
Minimal Residual Disease (MRD) Rate
The efficacy of this bispecific CD19/CD22-directed CAR T cell product will be monitored in each disease burden stratum by measuring peripheral blood MRD by next generation sequencing
Time frame: Months 1, 2, 3, 6, 9, and 12
Minimal Residual Disease (MRD) Rate
The efficacy of this bispecific CD19/CD22-directed CAR T cell product will be monitored in each disease burden stratum by measuring bone marrow MRD by flow cytometry and/or next generation sequencing.
Time frame: Months 1, 3, 6, and 12
CD19-Relapse
Cumulative incidence of CD19-relapse as determined by immunophenotype of leukemic blasts for subjects in each disease burden stratum will be calcualted using standard techniques using all enrolled patients and compared to published literature both from pre- and post-licensing clinical trials and/or reports.
Time frame: 1 year
Overall Survival
1-year overall survival (OS) rate in subjects with relapsed/refractory B-ALL treated with this bispecific CD19/CD22-directed CAR T cell product, stratified by disease burden.
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Time frame: 1 year
Progression Free Survival
1-year progression-free survival (PFS) rate in subjects with relapsed/refractory B-ALL treated with this bispecific CD19/CD22-directed CAR T cell product, stratified by disease burden.
Time frame: 1 year