Table 1 Study design characteristics and inclusion criteria for TRANSCEND versus ZUMA-1
Key study design features | TRANSCEND (liso-cel) | ZUMA-1 (axi-cel) |
|---|---|---|
Phase | 1 | 1/2 |
Design | Single arm | Single arm |
Blinding | Open label | Open label |
Centers | Multicenter | Multicenter |
Country | United States | Multiple (Israel and United States) |
Bridging therapy | Allowed | Not allowed |
PET-positive disease after bridging therapy | Confirmed | NA |
LDC | Yes | Yes |
Regimen and dosage of LDC | FLU (30 mg/m2/day for 3 d) and CY (300 mg/m2/day for 3 d), completed 2–7 d before infusion | FLU (30 mg/m2) and CY (500 mg/m2) on the fifth, fourth, and third day before infusion |
CAR T cell regimen and dosage | DL1S: 50 × 106 CAR+ T cells (25 × 106 CD8+ CAR+ T cells and 25 × 106 CD4+ CAR+ T cells) DL1D: 50 × 106 CAR+ T cells DL2S: 100 × 106 CAR+ T cells (50 × 106 CD8+ CAR+ T cells and 50 × 106 CD4+ CAR+ T cells) DL3S: 150 × 106 CAR+ T cells (75 × 106 CD8+ CAR+ T cells and 75 × 106 CD4+ CAR+ T cells) | Single infused dose of 2 × 106 CAR T cells per kg of body weight, with a maximum permitted dose of 2 × 108 CAR T cells |
Key inclusion criteria | TRANSCEND (liso-cel) | ZUMA-1 (axi-cel) | Action taken in TRANSCEND IPD and rationale |
|---|---|---|---|
NHL subtypes | DLBCL NOS, HGBCL, tFL, tiNHL, PMBCL, FL3B | DLBCL NOS,* HGBCL, PMBCL, tFL | Recategorized TRANSCEND to align with ZUMA-1 definition for DLBCL to retain TRANSCEND patients. Specifically, DLBCL NOS, HGBCL, and tiNHL from TRANSCEND were grouped together in “DLBCL” for comparison with “DLBCL” category in ZUMA-1 |
Age, years | ≥ 18 | ≥ 18 | None |
ECOG PS | ≤ 2† | ≤ 1 | None |
Prior lines of treatment | ≥ 2 | ≥ 2‡ | Redefined in TRANSCEND such that salvage chemotherapy and auto-HSCT were considered as 2 separate lines of therapy to align with ZUMA-1 definition |
Prior auto-HSCT | Allowed | Allowed, but not within 6 weeks of infusion | None |
Prior allo-HSCT | Allowed (not within 90 d of leukapheresis) | Not allowed | None |
Prior regimen required | Anthracycline and rituximab (or other CD20-targeted agents) | Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and an anthracycline-containing chemotherapy regimen | None |
Response to prior therapy | R/R disease after ≥ 2 lines of prior therapy or after auto-HSCT | No response to first-line therapy (primary refractory disease) OR no response to second- or later-line of therapy OR refractory after auto-HSCT (disease progression or relapsed ≤ 12 mo of auto-HSCT) | |
R/R to last therapy | Refractory: best response to last therapy as progressive disease, stable disease, or PR Relapsed: best response to last therapy as CR | Refractory: best response to last therapy§ as progressive disease or stable disease Relapsed: best response to last therapy§ of PR or CR | Redefined in TRANSCEND to align with ZUMA-1 definition. Specifically, in TRANSCEND, % refractory to last therapy was rederived to include progressive disease and stable disease, whereas % relapse was rederived to include PR and CR |
Absolute lymphocyte count | No minimum requirement¶ | ≥ 100/μL | Redefined in TRANSCEND to align with ZUMA-1 definition |
Absolute neutrophil count | No minimum requirement¶ | ≥ 1000/μL | None |
Platelet count | No minimum requirement¶ | ≥ 75,000/μL | None |
Hemoglobin | No minimum requirement¶ | Not reported | None |
Alanine aminotransferase | ≤ 5 × ULN | ≤ 2.5 × ULN | None |
Total bilirubin | < 2.0 mg/dL | ≤ 1.5 mg/dL | None |
Serum creatinine | ≤ 1.5 × ULN | Not reported | None |
CrCl | > 30 mL/min/1.73 m2 (Cockcroft-Gault) | ≥ 60 mL/min (Cockcroft-Gault) | Redefined in TRANSCEND to align with ZUMA-1 definition |
Dyspnea | Grade ≤ 1 by NCI CTCAE | Not clinically significant | None |
Oxygen saturation | ≥ 92% on room air | > 92% on room air | None |
LVEF | ≥ 40% | ≥ 50% | Redefined in TRANSCEND to align with ZUMA-1 definition |
Active CNS involvement | Secondary CNS involvement allowed | Not allowed | None |
History of another primary malignancy | Not allowed unless another primary malignancy has been in remission for ≥ 2 y | Not allowed unless disease free for ≥ 3 y | None |
Infections | Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or liso-cel administration | Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management | None |
Cardiovascular conditions or clinically significant cardiac disease | Within 6 mo of screening/enrollment | Within 12 mo of enrollment | None |