This is a pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCR-ζ and 4-1BB signaling domains (CART22/CART22-65s cells) in pediatric and young adult subjects with relapsed or refractory B cell acute lymphoblastic leukemia.
This is a single center, single arm, dual-cohort, open-label pilot study to determine the feasibility and safety of a single dose (administered as split fractions) of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4- 1BB) co-stimulatory domains (referred to as "CART22" and "CART22-65s" cells) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Cohort assignment will be dependent on the date of consent and confirmation of eligibility by a physician-investigator as follows: * Cohort 1: was closed to additional recruitment as of Protocol Version 8. All subjects who received CART22 cells will be retrospectively assigned to Cohort 1. * Cohort 2: was opened as of Protocol Version 8. All subjects assigned to Cohort 2 will receive CART22-65s cells given over 3 days. * Cohort 3: will open as of Protocol V12, with subjects enrolled sequentially after all infusion slots in Cohort 2 are filled. All subjects assigned to Cohort 3 will also receive CART22-65s cells, however the product will be administered over 2 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Subjects \<50kg will receive 0.2-1 x 10\^7 CART22 cells/kg as a split dose over three days as follows: Day 1, 10% fraction: 0.2-1x10\^6 CART22 cells/kg Day 2, 30% fraction: 0.6-3x10\^6 CART22 cells/kg Day 3, 60% fraction: 1.2-6x10\^6 CART22 cells/kg Subjects ≥50kg will receive 1-5x10\^8 CART22 cells as a split dose over three days as follows: Day 1, 10% fraction: 1-5x10\^7 CART22 cells/kg Day 2, 30% fraction: 0.3-1.5x10\^8 CART22 cells/kg Day 3, 60% fraction: 0.6-3x10\^8 CART22 cells/kg
Subjects \<50kg will receive 0.2-1 x 10\^7 CART22-65s cells/kg as a split dose over three days as follows: Day 1, 10% fraction: 0.2-1x10\^6 CART22-65s cells/kg Day 2, 30% fraction: 0.6-3x10\^6 CART22-65s cells/kg Day 3, 60% fraction: 1.2-6x10\^6 CART22-65s cells/kg Subjects ≥50kg will receive 1-5x10\^8 CART22-65s cells as a split dose over three days as follows: Day 1, 10% fraction: 1-5x10\^7 CART22-65s cells/kg Day 2, 30% fraction: 0.3-1.5x10\^8 CART22-65s cells/kg Day 3, 60% fraction: 0.6-3x10\^8 CART22-65s cells/kg
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS)
grade 3 and higher toxicity rate (toxicity possibly attributed to CART22)
Time frame: From date of dosing ( day 1 ) up 15 years
Percentage of manufacturing products that do not meet release criteria.
Product must pass for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination.
Time frame: 3 months
Overall Complete Remission Rate (ORR) at Day 28.
Includes CR and CR with incomplete blood count recovery (CRi)
Time frame: 4 months
Evaluate overall response rate (CR/CRi by or at Month 6) at Month 6.
Time frame: 9 months
Evaluate disease status at Month 6.
Time frame: 9 months
Overall survival (OS)
Time frame: 15 years
Duration of remission (DOR)
Time frame: 15 Years
Number of subjects with relapse free survival (RFS)
Time frame: 15 years
Number of subjects with event free survival (EFS).
Time frame: 15 years
Describe cause of death (COD) when appropriate
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Subjects \<50kg will receive 0.2-1 x 10\^7 CART22-65s cells as a split dose over two days as follows: Day 1, 25% fraction: 0.5-2.5x10\^6 CAR T cells/kg Day 2, 75% fraction: 1.5-7.5x10\^6 CAR T cells/kg Subjects ≥50kg will receive 1-5x10\^8 CART22-65s cells as a split dose over two days as follows: Day 1, 25% fraction: 0.25-1.25x10\^8 CART22-65s cells Day 2, 75% fraction: 0.75-3.75x10\^8 CART22-65s cells
Time frame: 15 years
Describe response in terms of minimal residual disease (MRD).
Percentage of patients who achieve a CR associated with minimal residual disease (MRD) negative bone marrow as determined by high sensitivity flow cytometry.
Time frame: 1 year
Incidence of any acute GVHD
Time frame: 15 year
Incidence of any grade II-IV aGVHD
Time frame: 15 year
Incidence any chronic GVHD.
Time frame: 15 year
Incidence any extensive, limited cGVHD.
Time frame: 15 year