Table 1 Reported clinical trials of gemtuzumab ozogamicin for acute myeloid leukemia
Trial name or NCT number (reference) | Phase | Age(number) | ND or R/R AML | Intervention | CR/CRi (CR) | DFS/EFS/RFS | OS | Early death (<  30 days) | Severe adverse events (Grade ≥ 3) |
|---|---|---|---|---|---|---|---|---|---|
[37] | III | 18–60 (595) | ND | GO (6 mg/m2 D4) + DA (3 + 7) | 76% (69%) | 5-yr: 43% | 5-yr: 46% | 5% | Grade 4 thrombocytopenia (48%), grade 4 or fatal nonhematologic induction toxicity (21%) |
ALFA-0701 [43] | III | 50–70 (271) | ND | GO (3 mg/m2 D1, 4, 7) + DA (3 + 7) | 81% (70%) | 17.3 mo 2-yr: 42% 3-yr: 40% | 28 mo 5-yr: 41% | 3.8% | Infection (78%), hemorrhage (23%), VOD (3.7%) |
MRC AML15 [45] | III | 0–71 (1113) | ND | GO (3 mg/m2 D1) + 2 cycles of DA, FLAG-Ida, or ADE | 85% (82%) | 5-yr: 39% | 5-yr: 43% | 11% | Myelosuppression (thrombocytopenia and neutropenia with unknown incidence) |
NCRI AML16 [23] | III | 51–84 (1115) | ND | GO (3 mg/m2 D1) + DA (3 + 10 then 3 + 8) or DC (daunorubicin D1, 3, 5 + clofarabine D1–5) | 69% (60%) | 3-yr: 21% | 2-yr: 35% 3-yr: 25% | 9% | Gastrointestinal events (19%), liver chemistry abnormalities (17%) |
NCRI AML17 [38] | III | 0–81 (788) | ND | GO (3 or 6 mg/m2 D1) + DA (3 + 10) or ADE (10 + 3 + 5); | 3 mg GO: 89% (82%) 6 mg GO: 86% (76%) | 3 mg GO: 4-yr 44% 6 mg GO: 4-yr 38% | 3 mg GO: 4-yr 50% 6 mg GO: 4-yr 47% | 3 mg GO: 3% 6 mg GO: 7% | 3 mg vs 6 mg GO: VOD (0.5% vs 5.6%), increased ALT (17% vs 7%) |
GOELAMS AML 2006 IR [46] | III | 18–60 (238) | ND | GO (6 mg/m2 D1) + DA (3 + 7) | CR 91% | 51% | 53% | 10% | Hepatotoxicity (23%), severe VOD 4 cases |
NCT00909168 [50] | II | 18–65 (130) | ND | GO (3 mg/m2 D6) + FLAG-Ida (fludarabine 30 mg/m2 and cytarabine 2 mg/m2 D1–5, idarubicin 10 mg/m2 D1, 3, 5) | 85% (82%) | 1-yr: 77% 2-yr: 58% 5-yr: 52% | 1-yr: 80% 2-yr: 63% 5-yr: 62% | 3% | AEs of all grades: fever of unknown origin (52%), bacteremia (26%), HSV infection (18%), pneumonia (17%), mucositis (17%) |
EORTC-GIMEMA AML-17 [51] | III | 61–75 (472) | ND | GO (6 mg/m2 D1, 15) + MICE (mitoxantrone 7 mg/m2 D1, 3, 5; etoposide 100 mg/m2 D1–3; and cytarabine 100 mg/m2 D1–7) | 45% (36%) | – | 7.1 mo | 17% | Infection (37%), neutropenic fever (26%), hepatotoxicity (15%), bleeding (11%) |
EORTC-GIMEMA AML-19 [21] | III | 61–75 (237) | ND, not fit for chemotherapy | GO (6 mg/m2 D1 + 3 mg/m2 D8) | 27% (15%) | – | 4.9 mo, 1-yr: 24% | 11% | Infections (35%), febrile neutropenia (18%), bleeding (13%) |
MyloFrance 1 [41] | II | 22–80 (57) | First relapse | GO (3 mg/m2 D1, 4, 7) | 33% (26%) | 11 mo | 8.4 mo | 7% | Sepsis (31.5%), fever (15.8%), rash (10.5%), pneumonia (7%), bleeding (7%) |
NCT00143975 [54] | II | 18–60 (93) | Refractory to 1 cycle of induction | GO (1 mg/m2 D1) + ATRA (45 mg/m2 D4–6, 15 mg/m2 D7–28) + cytarabine (3 mg/m2/12h D1–3) + mitoxantrone (12 mg/m2 D2–3) | 51% (30%) | – | 16 mo 4-yr: 32% | 3% | Septicemia (46%), pneumonia (22%), gastrointestinal events (15%) |
NCT00766116 [55] | I/II | 29–82 (50) | R/R | GO (6 mg/m2 D7, 21) + Azacytidine (75 mg/m2 D1–6) | Phase I: 50% (25%) Phase II: 24% (11%) | – | – | 0 | Febrile neutropenia (75%), infections (17%) |
NCT00895934 [56] | I/II | 50–79 (52) | R/R | GO (3 mg/m2 D4, 8) + azacytidine (75 mg/m2 D1–7) + vorinostat (400 mg D1–9) | Phase I: 40% Phase II: 42% (21%) | – | – | 7% | Febrile neutropenia (75%), infections (31%) |
NCT00882102 (Daver et al. 2016) [57] | II | 27–89 (110) | ND and R/R | GO (3 mg/m2 D5) + decitabine (20 mg/m2 D1–5) q14d | 35% | ND: 7 mo R/R: 1 mo | ND: 7 mo R/R: 3.5 mo | – | Febrile neutropenia (45%), infections (21%) |
NCT00801489 [61] | II | 19–76 (45) | ND CBF AML | GO (3 mg/m2 D1) + FLAG (fludarabine 30 mg/m2 and cytarabine 2 mg/m2 D1–5, G-CSF 5 μg/kg D1) | 95% (91%) | 3-yr: 85% | 3-yr: 78% | 4% | Fever of unknown origin (24%), pneumonia (18%), sepsis (10%), transaminase elevations (8%) |