Skip to main content

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
  1. 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