. 2020 Dec 7;9:285. doi: 10.1186/s13643-020-01540-1

Table 1.

Characteristics of included studies

Author, year Trial name/number	Population selection criteria	Intervention N randomised and details	Control N randomised and details	Intervention baseline age (yrs) and type of AML	Control baseline age (yrs) and type of AML	Outcomes reported and median follow-up
Rollig C, 2015 [15] SORAML; NCT00893373; Phase 2, Germany	Aged 18–60 yrs, newly diagnosed de novo or secondary AML (excluding APL)	Sorafenib 400 mg twice daily plus standard chemo—ind/cons/main up to 12 mths N = 138^a	Placebo plus standard chemo N = 138^a	Median age (range): 50 (43–46); de novo AML: NR; 2° AML: 10%; High-risk MDS: NR	Median age (range): 50 (44–55); de novo AML: NR; 2° AML: 15%; High-risk MDS: NR	1°: EFS 2°: RFS, OS, CR, tox FU: 36 mths
Serve H, 2013 [16] NCT00373373; Phase 2, Germany	Aged > 60 yrs, de novo or secondary AML or AML from MDS (excluding FAB type M3)	Sorafenib 400 mg twice daily plus intensive chemo—ind/cons N = 104^a	Placebo plus intensive chemo N = 97^a	Median age (range): 67.5 (61–78); de novo AML: 60%; 2° AML: 40%; High-risk MDS: NR	Median age (range): 69 (61–80); de novo AML: 61%; 2° AML: 39%; High-risk MDS: NR	1°: EFS 2°: OS, CR rate, tolerability FU: 29.3 mths
Knapper S, 2017 [17] AML15; ISRCTN17161961; Phase 3, UK Denmark, NZ	Aged < 60 yrs, de novo or secondary AML, FLT3 mutation (excluding APL)	Lestaurtinib 80 mg, twice daily after each of 4 courses of intensive chemo—ind/cons N = 88	Intensive chemo N = 87	Median age (range): 48 (16–66); de novo AML: 95%; 2° AML: 3%; High-risk MDS: 0%	Median age (range): 46 (16-65); de novo AML: 97%; 2° AML: 5%; High-risk MDS: 0%	1°: OS/RFS 2°: CR, CRi, OS, haem recovery times, tox, resource use FU: 50.5 mths
Knapper S, 2017 [17] AML17; ISRCTN55675535 Phase 3, UK Denmark, NZ	Aged < 60 yrs, de novo or secondary AML, FLT3 mutation (excluding APL)	Lestaurtinib 80 mg, twice daily plus 1st line intensive chemo—ind/cons N = 212	Placebo plus 1st line intensive chemo N = 113	Median age (range): 50 (5–68); de novo AML: 93%; 2° AML: 5%; High-risk MDS: 2%	Median age (range): 50 (6–65); de novo AML: 92%; 2° AML: 5%; High-risk MDS: 3%	1°: OS/RFS 2°: CR, CRi, OS, haem recovery times, tox, resource use FU: 50.5 mths
Levis M, 2011 [18] Cephalon-204; NCT00079482; Phase 2, Australia, Canada, EU, Israel, NZ, Russia, Ukraine, USA	Aged ≥ 18 yrs, AML with 1st relapse after 1st remission of 1–24 mths, FLT3 mutation	Salvage chemo followed by lestaurtinib 80 mg, twice daily N = 112	Salvage chemo N = 112	Median age (range): 59 (20–81); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	Median age (range): 54 (21–79); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	1°: CR, CRp 2°: OS, PR, tox, tolerability FU: not reported
Stone RM, 2017 [19] RATIFY calgb 10603; NCT00651261; Phase 3, Canada, USA	Aged 18–59 yrs, newly diagnosed AML, FLT3 mutation (excluding APL)	Midostaurin 50 mg twice daily plus standard chemo—ind/cons/main up to 12 mths N = 360	Placebo 50 mg twice daily plus standard chemo N = 357	Median age (range): 47.1 (19–60); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	Median age (range): 48.6 (18–61); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	1°: OS 2°: EFS, OS, CR rate, DFS, HCT rate FU: 59 mths
Perl AE, 2019 [21] ADMIRAL; NCT02421939; Phase 3, 14 countries	Aged > 18 yrs, relapsed or refractory AML, FLT3 mutation	Gilteritinib 120 mg, once daily in 28-day cycles N = 247	Salvage chemo N = 124	Median age (range): 62.0 (20.0–84.0); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	Median age (range): 61.5 (19.0–85.0); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	1°: OS, CR 2°: EFS, tox FU: 17.8 mths
Cortes JE, 2019 [20] QuANTUM-R; NCT02039726; Phase 3, 19 countries	Aged > 18 yrs, relapsed or refractory AML, FLT3-ITD mutation (excluding APL)	Quizartinib 20–60 mg as appropriate, once daily in continuous 28-day cycles N = 245	Salvage chemo N = 122	Median age (range): 55.0 (46.0–65.0); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	Median age (range): 57.5 (44.0–66.0); de novo AML: NR; 2° AML: NR; High-risk MDS: NR	1°: OS 2°: EFS, CR, early death (30- and 60-day mortality) FU: 23.5 mths

Author, year
Trial name/number

Population selection criteria

Intervention N randomised and details

Control N randomised and details

Intervention baseline age (yrs) and type of AML

Control baseline age (yrs) and type of AML

Outcomes reported and median follow-up

Rollig C, 2015 [15]

SORAML; NCT00893373;

Phase 2, Germany

Aged 18–60 yrs, newly diagnosed de novo or secondary AML

(excluding APL)

Sorafenib 400 mg twice daily plus standard chemo—ind/cons/main up to 12 mths

N = 138^a

Placebo plus standard chemo

N = 138^a

Median age (range):

50 (43–46);

de novo AML: NR;

2° AML: 10%;

High-risk MDS: NR

Median age (range):

50 (44–55);

de novo AML: NR;

2° AML: 15%;

High-risk MDS: NR

1°: EFS

2°: RFS, OS, CR, tox

FU: 36 mths

Serve H, 2013 [16]

NCT00373373;

Phase 2, Germany

Aged > 60 yrs, de novo or secondary AML or AML from MDS

(excluding FAB type M3)

Sorafenib 400 mg twice daily plus intensive chemo—ind/cons

N = 104^a

Placebo plus intensive chemo

N = 97^a

Median age (range): 67.5 (61–78);

de novo AML: 60%;

2° AML: 40%;

High-risk MDS: NR

Median age (range):

69 (61–80);

de novo AML: 61%;

2° AML: 39%;

High-risk MDS: NR

1°: EFS

2°: OS, CR rate, tolerability

FU: 29.3 mths

Knapper S, 2017 [17]

AML15; ISRCTN17161961;

Phase 3, UK Denmark, NZ

Aged < 60 yrs, de novo or secondary AML, FLT3 mutation

(excluding APL)

Lestaurtinib 80 mg, twice daily after each of 4 courses of intensive chemo—ind/cons

N = 88

Intensive chemo

N = 87

Median age (range):

48 (16–66);

de novo AML: 95%;

2° AML: 3%;

High-risk MDS: 0%

Median age (range):

46 (16-65);

de novo AML: 97%;

2° AML: 5%;

High-risk MDS: 0%

1°: OS/RFS

2°: CR, CRi, OS, haem recovery times, tox, resource use

FU: 50.5 mths

Knapper S, 2017 [17]

AML17; ISRCTN55675535

Phase 3, UK Denmark, NZ

Aged < 60 yrs, de novo or secondary AML, FLT3 mutation

(excluding APL)

Lestaurtinib 80 mg, twice daily plus 1st line intensive chemo—ind/cons

N = 212

Placebo plus 1st line intensive chemo

N = 113

Median age (range):

50 (5–68);

de novo AML: 93%;

2° AML: 5%;

High-risk MDS: 2%

Median age (range):

50 (6–65);

de novo AML: 92%;

2° AML: 5%;

High-risk MDS: 3%

1°: OS/RFS

2°: CR, CRi, OS, haem recovery times, tox, resource use

FU: 50.5 mths

Levis M, 2011 [18]

Cephalon-204; NCT00079482;

Phase 2, Australia, Canada, EU, Israel, NZ, Russia, Ukraine, USA

Aged ≥ 18 yrs, AML with 1st relapse after 1st remission of 1–24 mths, FLT3 mutation

Salvage chemo followed by lestaurtinib 80 mg, twice daily

N = 112

Salvage chemo

N = 112

Median age (range):

59 (20–81);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

54 (21–79);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: CR, CRp

2°: OS, PR, tox, tolerability

FU: not reported

Stone RM, 2017 [19]

RATIFY calgb 10603; NCT00651261;

Phase 3, Canada, USA

Aged 18–59 yrs, newly diagnosed AML, FLT3 mutation

(excluding APL)

Midostaurin 50 mg twice daily plus standard chemo—ind/cons/main up to 12 mths

N = 360

Placebo 50 mg twice daily plus standard chemo

N = 357

Median age (range):

47.1 (19–60);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

48.6 (18–61);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: OS

2°: EFS, OS, CR rate, DFS, HCT rate

FU: 59 mths

Perl AE, 2019 [21]

ADMIRAL;

NCT02421939;

Phase 3, 14 countries

Aged > 18 yrs, relapsed or refractory AML, FLT3 mutation

Gilteritinib 120 mg, once daily in 28-day cycles

N = 247

Salvage chemo

N = 124

Median age (range):

62.0 (20.0–84.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

61.5 (19.0–85.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: OS, CR

2°: EFS, tox

FU: 17.8 mths

Cortes JE, 2019 [20]

QuANTUM-R; NCT02039726;

Phase 3, 19 countries

Aged > 18 yrs, relapsed or refractory AML, FLT3-ITD mutation

(excluding APL)

Quizartinib 20–60 mg as appropriate, once daily in continuous 28-day cycles

N = 245

Salvage chemo

N = 122

Median age (range):

55.0 (46.0–65.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

Median age (range):

57.5 (44.0–66.0);

de novo AML: NR;

2° AML: NR;

High-risk MDS: NR

1°: OS

2°: EFS, CR, early death (30- and 60-day mortality)

FU: 23.5 mths

Abbreviations: AML acute myeloid leukaemia, APL acute promyelocytic leukaemia, chemo chemotherapy, cons consolidation therapy, CR complete remission, CRi CR with incomplete haematologic recovery, CRp CR with incomplete platelet recovery, DFS disease-free survival, EFS event-free survival, FAB French-American British (classification system), FLT3 fms-like tyrosine kinase 3, FU follow-up, HCT haematopoietic cell transplant, ind induction therapy, main maintenance therapy, MDS myelodysplastic syndrome, mths months, NR not reported, NZ New Zealand, OS overall survival, PR partial remission, RFS relapse-free survival, tox toxicity, yrs years, 1° primary, 2° secondary

^aN includes patients who were randomised and untreated and/or not included in the individual trial analyses