Table 3.
Major clinical trials on anti-CD19 CAR T cell therapy
| Institution and trial no. | Costimulatory domain and gene transfer | Patient | Lymphodepleting chemotherapy | Cell dose | Outcomes |
|---|---|---|---|---|---|
| MSKCC NCT01044069 [53] |
CD28, γ-retrovirus | Adults with R/R ALL including Ph + ALL, n = 44 | Cy or flu/cy | 1–3 × 106 cells/kg | CR: 36/43 (84%) with 29/35 (83%) of responders negative for MRD; OS: 76% (MRD-CR cohort) and 14% (MRD + CR cohort) at 6 months |
| NCI NCT01593696 [54] |
CD28, γ-retrovirus | Children and young adults with R/R ALL, n = 51 | Cy, low-dose flu/cy, FLAG, ifosfamide/etoposide or high-dose flu/cy | 0.03 × 106–3 × 106 cells/kg | CR: 31/51 (60.8%) with 28/31 (90%) of responders negative for MRD OS: 34.7% (receiving flu/cy) at 38 months LFS: 49.5% (MRD- CR) at 18 months LFS: 62% (MRD- CR cohort having a subsequent HSCT) at 18 months |
| Multicenter studies NCT02614066, NCT02625480 [55] |
CD28, γ-retrovirus | R/R ALL aged ≥ 18 years (ZUMA-3) or 2–21 years (ZUMA-4) with ≥ 25% marrow blasts Ph+ ALL and low-burden central nervous system disease are eligible |
Flu/cy | 1 or 2 × 106 anti-CD19 CAR T cells/kg | CR: 5/5 (100%) |
| FHCRC NCT01865617 [72] |
4-1BB, Lentivirus | Adult with R/R ALL, n = 30 29 evaluable |
Cy ± etoposide or cy/flu | 2 × 105 or 2 × 106 or 2 × 107 cells/kg 1:1 CD4+:CD8+ |
CR: 27/29 (93%) |
| UPenn/CHOP NCT01626495 [56] |
4-1BB, Lentivirus | Children and young adults with R/R ALL, n = 53 | Investigator’s choice | 1–17.4 × 106 cells/kg | CR: 50/53 (94%) with 47/50 (94%) of responders negative for MRD OS: 78% at 12 months RFS: 72% at 6 months |
| ELIANA (global trial) NCT02435849 [57] |
4-1BB, Lentivirus | Children and young adults with R/R ALL, 29 pts reaching D28 prior to the data cutoff | Flu/cy | 0.2–4 × 106 cells/kg | CR: 24/29 (83%) with all of responders negative for MRD |
| ENSIGN (US multicenter trial) NCT02228096 [58] |
4-1BB, Lentivirus | Children and young adults with R/R ALL, n = 29 | Flu/cy, or none due to leukopenia | 2–5 × 106 cells/kg for ≤ 50 kg, 1–2.5 × 108 cells for > 50 kg | ORR (CR + CRi): 20/29 (69.0%) with 18/29 (62.1%) responders negative for MRD RFS: 66.4% at 6 months OS: 75.7% at 6 months |
| UPenn/CHOP NCT02374333 [74] |
4-1BB, Lentivirus humanized anti-CD19 scFv domains | Children and young adults with R/R ALL, with or without prior exposure to a CAR T cell product, n = 30 | Flu/cy | No mention | CR: 26/30 (87%) CR for patients previously treated with CAR T: 7/11(64%) with 5/7 (71%) of responders negative for MRD CR for patients with no prior exposure to CAR T: 19/19 (100%) with 19/19 (100%) of responders negative for MRD |
MSKCC Memorial Sloan Kettering Cancer Center, NCI National Cancer Institute, FHCRC Fred Hutchinson Cancer Research Center, UPenn University of Pennsylvania, CHOP Children’s Hospital of Philadelphia, Cy cyclophosphamide, Flu fludarabine, FLAG fludarabine, high-dose cytarabine, and G-CSF