Table 3 Major clinical trials on anti-CD19 CAR T cell therapy
From: Novel immunotherapies for adult patients with B-lineage acute lymphoblastic leukemia
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 |