Table 1.
Clinical trials for CD19‐directed CAR T cell therapy
| Clinical trial | ELIANA trial (NCT02435849) | JULIET trial (NCT02445248) | ZUMA‐1 trial (NCT02348216) | TRANSCEND NHL 001 trial (NCT 02631044) | ZUMA‐2 trial (NCT02601313) |
|---|---|---|---|---|---|
| Drug | Tisagenlecleucel (Kymriah, Novartis) | Tisagenlecleucel (Kymriah, Novartis) | Axicabtagene ciloleucel (Yescarta, Kite) | Lisocabtagene maraleucel (Juno Therapeutics) | Axicabtagene ciloleucel KTE‐X19 (Yescarta, Kite) |
| Target | CD19 | CD19 | CD19 | CD19 | CD19 |
| Stimulatory and co‐stimulatory domains | CD3 ζ and 1‐4BB | CD3 ζ and 1‐4BB | CD3 ζ and CD28 | CD3 ζ and 1‐4BB | CD3 ζ and CD28 |
| Study design | Single‐arm, multicentered, unblinded phase 2 | Single‐arm, multicenter, open labeled, phase 2 | Single‐arm, multicenter, unblinded, phase 1–2 | Single‐arm, multicenter, multicohort, unblinded, phase 1–2 | Multicenter, phase 2 trial |
| Population | Patients within 3–23 years old with R/R B‐ALL | Patients 18 years or older with R/R DLBCL who received at least 2 prior lines of therapy (de novo DLBCL or from transformed FL, and high‐grade B‐cell lymphoma with MYC rearrangement plus rearrangement of Bcl2, Bcl6 or both) | Patients 18 years or older with refractory large B cell lymphoma (DLBCL, transformed follicular lymphoma, primary mediastinal B cell lymphoma) | Patients 18 years or older with R/R large B‐cell lymphoma (transformed or de novo DLBCL, primary mediastinal B cell lymphoma and high‐grade B‐cell lymphoma with MYC rearrangement plus rearrangement of Bcl2, Bcl6 or both), FL grade 3B or relapsed MCL | Patients 18 years or older with R/R mantle cell lymphoma |
| Previous lines of treatment, range (median) | 1–8 (3) | 1–8 (not reported) | 2–4 (3) | 2–4 (3) | 1–5 (3) |
| Previous autologous stem cell transplantation, n (%) | 46 (61) | 18 (33) | Not reported | 90 (33) | 29 (43) |
| Lymphodepletion chemotherapy | Fludarabine 30 mg/m2 IV (daily doses for 4 doses) and cyclophosphamide 500 mg/m2 IV (daily doses for 2 doses) | Fludarabine 25 mg/m2 IV (daily doses for 3 days) and cyclophosphamide 250 mg/m2 IV (daily doses for 3 doses) or bendamustine 90 mg/m2 IV (daily doses for 2 days) | Fludarabine 30 mg/m2 IV (daily doses for 3 days) and cyclophosphamide 500 mg/m2 IV (daily doses for 3 doses | Fludarabine 30 mg/m2 IV (daily doses for 3 doses) and cyclophosphamide 300 mg/m2 IV (daily doses for 3 doses) | Fludarabine 30 mg/m2 IV (daily doses for 3 days) and cyclophosphamide 500 mg/m2 IV (daily doses for 3 doses |
| T cell dose | Single dose of 0.2–5 × 106 cells/kg (patients < or = 50 kg) or 0.1–2.5 × 106 cells/kg (patients > 50 kg) | Single dose of 0.1–6 × 108 cells (median 3 × 108 cells) | Single dose of 2 × 106 cells/kg (minimum 1 × 106 cells/kg) |
Sequential infusions
(Median 91 × 106 T cells; range 44–156 × 106 T cells) |
Single dose of 2 × 106 cells/kg (minimum 1 × 106 cells/kg) |
| Primary endpoints | Overall remission rate (CR/CRi) by month 3 | Best overall response rate (CR + PR) | Objective response (CR + PR) | Best overall response rate (CR + PR), incidence of adverse events and probability of dose‐limiting toxicities | Objective response (CR+ PR) |
| Response rates | ORR 81% (CR 60% and CRi 21%) | Best ORR 52% (CR 40% and PR 12%) | Objective response 83% (CR 58% and PR 25%) |
Objective response
|
Objective response 93% (CR 67% and PR 27%) |
| Adverse events | |||||
| B‐cell aplasia | All patients with response to treatment | Only one patient had normal B‐cell count before infusion | 25% had persistent B cell aplasia at 24 months post infusion | 92% had B cell aplasia at baseline | None |
| CRS, n (%) | 58 (77) | 64 (58) | 100 (92) | 113 (42) | 62 (91) |
| Neurologic events, n (%) | 30 (40) | 23 (21) | 72 (67) | 80 (30) | 43 (63) |
| Pyrexia, n (%) | 30 (40) | 39 (35) | 94 (87) | 45 (17) | 62 (91) |
| Febrile neutropenia, n (%) | 27 (36) | 18 (16) | 39 (36) | 25 (9) | Not reported |
| Hypotension, n (%) | 22 (29) | 29 (26) | 63 (58) | 60 (22) | 35 (51) |
| Elevated AST, n (%) | 20 (27) | Not reported | 19 (18) | Not reported | 21 (31) |