Table 1.
Selected clinical trials of CAR T cells in B-cell acute lymphoblastic leukemia.
| Setting | Target | Product | Costimul. domain | Generation | Vector | Population infused | Response | Durable remission rate | CRS (gr.3/4) | NTX (gr.3/4) | Institute/Company | Clinical trial | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| B-ALL | CD19 | Tisagenlecleucel (CTL019, Kymriah®) | 4-1BB | Second (2nd) | Lentiviral | 75, R/R pediatric/AYA B-ALL (up to 25 yo) |
ORR 81% CR 60% |
RFS 80% at 6 mo 59% at 12 mo |
47%¥ | 13%± | UPenn/Novartis | ELIANA NCT02435849 multicenter phase II |
(21) |
| KTE-X19 | CD28 | Second (2nd) | Retroviral | 45, R/R adult B-ALL | ORR 82% CR 73% |
Median DOR 12.9 mo | 29%§ | 38%± | Kite, Gilead | ZUMA-3 NCT02614066 multicenter phase I/II |
(30) | ||
| 24, R/R pediatric/AYA B-ALL | CR + CRi rate 64–100% (related to CART dose) |
ongoing remission 25–56% (related to CART dose) |
22–75%§ (related to CART dose) | 11–36%± (related to CART dose) | ZUMA-4 NCT02625480 Multicenter phase I/II |
(32) | |||||||
| 19-28z-CAR | CD28 | Second (2nd) | Retroviral | 53, R/R adult B-ALL | CR 83% | Unknown | 26%¶ | 42%± | MSKCC/Juno |
NCT01044069 Phase I |
(33) | ||
| CD19-28z-CAR | CD28 | Second (2nd) | Retroviral | 19, R/R pediatric/AYA B-ALL (up to 30 yo) |
CR 67% | 12-mo LFS 78.8% | 28%± | 5%¬ | NCI |
NCT01593696 Phase I |
(40) | ||
| CD4+/CD8+ CD19-BBz-CAR | 4-1BB | Second (2nd) | Lentiviral | 45, R/R pediatric/AYA B-ALL | MRD− CR 89% | Unknown | 23%± | 21%± | SCH | PLAT-02 NCT02028455 Phase I/II |
(41) | ||
| CD19-BBz.EGFRt-CAR | 4-1BB | Second (2nd) | Lentiviral | 30, R/R adult B-ALL | CR 93% MRD neg 86% |
Unknown | 23%§ | 50%± | FHCRC |
NCT01865617 Phase I/II |
(42) | ||
| UCART19 | 4-1BB | Allogeneic CAR T cells, gene editing with TALEN | Lentiviral | 7, R/R pediatric B-ALL | CR + CRi 88% MRD neg 86% |
Ongoing remission 28% | 15%† | 0% † | MDACC, UCL etc./Servier | PALL NCT02808442 Phase I |
(43) | ||
| 13, R/R Adult B-ALL |
Ongoing remission 21% | CALM NCT02746952 Phase I |
|||||||||||
| CD22 | CD22-BBz-CAR | 4-1BB | Second (2nd) | Lentiviral | 21, R/R pediatric/adult B-ALL | CR 73% | Median DOR 6 mo |
0%± | 0%± | NIH |
NCT02315612 Phase I |
(44) |
, Penn/CHOP grading scale;
, NCI 2014 consensus grading scale modified by Lee DW et al. (45);
, MSKCC criteria;
, CTCAE v4.02;
, CTCAE v4.03;
CTCAE v5.0.
ALL, acute lymphoblastic leukemia; R/R, relapse/refractory; AYA, adolescent and young adult; ORR, overall response rate; CR, complete remission; CRi, complete remission with incomplete hematologic recovery; MRD, minimal residual disease; mo, months; DOR, duration of response; EFS, event-free survival; RFS, relapse-free survival; LFS, leukemia-free survival; DFS, disease-free survival; NR, not reached; CRS, cytokine release syndrome; NTX, neurotoxicity; UPenn, University of Pennsylvania Hospital; SCH, Seattle Children's Hospital; FHCRC, Fred Hutchinson Cancer Research Center; MSKCC, Memorial Sloane Kettering Cancer Center; NCI, National Cancer Institute; MDACC, MD Anderson Cancer Center; UCL, University College of London.