Table 2.
Summary of CD19 CAR-T cell therapy clinical trials for relapsed or refractory pediatric (children and young adults) ALL. AE adverse event, BBH Beijin Boren Hospital, CAR chimeric antigen receptor, CR complete remission, CRS cytokine release syndrome, CHOP Children’s Hospital of Pennsylvania, Cy cyclophosphamide, DFCI Dana Farber Cancer Institute, FC flow cytometry, Flu fludarabine, ICANS immune effector cell-associated neurotoxicity syndrome, MFC multiparameter flow cytometry, MSKCC Memorial Sloan Kettering Cancer Center, MOF multiorgan failure, MRD minimal residual disease, NA not applicable, NIH National Institute of Health, NCI National Cancer Institute, TCS CD8+ and CD4+ T cell selection, UPENN University of Pennsylvania.
| Institution | CHOP/UPENN1 | Multicenter6 | NIH/NCI | Seattle Children’s5 | MSKCC/DFCI8 | BBH26 | |
|---|---|---|---|---|---|---|---|
| Target Antigen | CD19 | CD19 | CD22 | CD19 | CD22 | ||
| Trial identification |
NCT01626495
NCT01029366 |
ELIANA NCT02435849 |
NCT01593696 2 | NCT02315612 46 | PLAT-02 NCT02028455 |
NCT01860937 | hiCTR-OIC-17013523 |
| Number of subjects infused | 30 | 75 | 21 | 58 | 43 | 25 | 34 |
| CAR T-cell product | CTL019 (tisagenlecleucel) | MSGV-FMC63-28Z | CD22.BB.z-CAR | SCRI-CAR19v1 | 19-28z | YK-CD22BB-002 | |
| Co-stimulatory domain | 4-1BB | CD28 | 4-1BB | 4-1BB | CD28 | 4-1BB | |
| scFv | FMC63 | FMC63 | m971 | FMC63 | SJ25C1 | YK | |
| CAR T-cell dose | 1-17x106/kg | 0.2-5.4×106/kg | 1x106/kg 3 x 106/kg |
1x106/kg
bulk 1x106/kg TCS 3 x 105/kg TCS (de-escalated due to toxicity) |
0.5 x106/kg 1 x 106/kg 5 x106/kg 10 x 106/kg |
1 x 106/kg | No prior allo: median dose, 7.5 ×
105/kg (range, 0.3–34.7 ×
105/kg) Prior allo: median dose, 1 × 105/kg (range, 0.2 to 10 × 105/kg |
| Lymphodepletion | Cy-based, 83% Cy 500mg/m2 x1 + Flu 25mg/m2x3 in 43% |
Cy 500mg/m2x + Flu
30mg/m2x4 or Ara-c 500mg/m2x2 + etoposide 150mg/m2x3 |
Cy 900mg/m2x1 + Flu 25mg/m2x3 | Cy 2-4mg/m2x1 Cy 500mg/m2x2+30mg/m2x4 |
Cy 3 g/m2 +/− Flu
(n=3), 68% Cy ≤1.5 g/m2 +/− Flu (n=3), 32% |
Cy 250mg/m2x3 + Flu 30mg/m2x3 | |
| Median BM blasts prior to lymphodepletion | Detectable disease by morphology in 80% | 74% | 25.5% | >5% in 76% | >25% in 51% | 4% | 63% |
| MRD negative CR by MFC | 73% | 81% | 57% | 60% | 89% | 88% | 76% |
| Median CRS duration (days) | Not reported | 8 | 5 | 5 | Not reported | Not reported | 8 |
| Median ICANS duration (days) | 2-3 | 50% resolved within 10 days 75% within 18 days 4 patients had no resolution |
Not reported. Two weeks in one patient | Not reported | Not reported | Not reported | 7 |
| Seizures (n) | 1 | 1 | 0 | 0 | 5 | 5 | 1 |
| Cerebral edema (n) | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Deaths attributed to CAR-T cell therapy (n) | 0 | 0 | 0 | 2 (3%) | 0 | 1 (4%) | 4 (12%) |
| Causes of death | NA | 0 | NA | Sepsis with MOF Severe CRS with ARDS | NA | Sepsis with MOF after severe CRS | Grade 5 CRS (n=1) SOS (n=1) Seosis with MOF (n=2) |