Selection of RCTs comparing intensive chemotherapy with venetoclax-based nonintensive treatment in newly diagnosed fit patients
| Target population/AML subgroup* . | Age (years) . | Experimental agent/intervention . | Experimental arm . | Control arm . | Primary endpoint† . | Planned patient number . | Name PI, country (cooperative group) . | Registry number . |
|---|---|---|---|---|---|---|---|---|
| • All comers • No CBF • No NPM1 mut in <60 y • No FLT3-ITD or –TKD | ≥18 | Venetoclax + azacitidine | Venetoclax + azacitidine | 7 + 3‡ or CPX-351 | EFS | 172 | Fathi, USA | NCT04801797 |
| • NPM1 mut • No FLT3-ITD | ≥60 or relevant comorbidity | Venetoclax + LDAC | Venetoclax + LDAC | DA+GO | Modified EFS | 186 | Dillon, UK (NCRI) | EudraCT 2020-000273-24, ISRCTN 15567173 |
| • NPM1 mut • No FLT3-ITD | 18-70 | Venetoclax + azacitidine | Venetoclax + azacitidine | DA + GO | Modified EFS | 146 | Röllig, Germany (SAL-AMLCG) | EudraCT 2021-00348-26, NCT05904106 |
| • Adverse risk (ELN2017) • No FLT3-ITD or –TKD • No t(9;22) | 18-59 | 7 + 3/CPX-351 + venetoclax or azacitidine + venetoclax | 7 + 3/CPX-351 + venetoclax or azacitidine + venetoclax | 7 + 3 or CPX-351 | MRD after induction | 268 | Shami/NCI, USA, Canada (SWOG) | NCT05554406 |
| • Intermediate risk • No FLT3-ITD or -TKD | 18-59 | 7 + 3 + venetoclax or azacitidine + venetoclax | 7 + 3 + venetoclax or azacitidine + venetoclax | 7 + 3 | MRD after induction | 153 | Savoie/NCI, Canada, USA (CCTG) | NCT05554393 |
| • All comers | 18-59 | Venetoclax | Venetoclax + decitabine | 7 + 3 | ORR§ | 188 | Suning, China | NCT05177731 |
| • TP53 mut | ≥18 | Magrolimab | Magrolimab + azacitidine | Venetoclax + azacitidine or 7 + 3 | OS | 356 | Gilead, USA | NCT04778397 |
| • Adverse risk, intermediate risk, and 50-70 y • No FLT3-ITD | 18-70 | Magrolimab | Magrolimab + venetoclax + azacitidine | DA, DA + GO, CPX-351, or FLAG-Ida | EFS | 164 | Craddock, UK (NCRI) | ISRCTN71474257 |
| Target population/AML subgroup* . | Age (years) . | Experimental agent/intervention . | Experimental arm . | Control arm . | Primary endpoint† . | Planned patient number . | Name PI, country (cooperative group) . | Registry number . |
|---|---|---|---|---|---|---|---|---|
| • All comers • No CBF • No NPM1 mut in <60 y • No FLT3-ITD or –TKD | ≥18 | Venetoclax + azacitidine | Venetoclax + azacitidine | 7 + 3‡ or CPX-351 | EFS | 172 | Fathi, USA | NCT04801797 |
| • NPM1 mut • No FLT3-ITD | ≥60 or relevant comorbidity | Venetoclax + LDAC | Venetoclax + LDAC | DA+GO | Modified EFS | 186 | Dillon, UK (NCRI) | EudraCT 2020-000273-24, ISRCTN 15567173 |
| • NPM1 mut • No FLT3-ITD | 18-70 | Venetoclax + azacitidine | Venetoclax + azacitidine | DA + GO | Modified EFS | 146 | Röllig, Germany (SAL-AMLCG) | EudraCT 2021-00348-26, NCT05904106 |
| • Adverse risk (ELN2017) • No FLT3-ITD or –TKD • No t(9;22) | 18-59 | 7 + 3/CPX-351 + venetoclax or azacitidine + venetoclax | 7 + 3/CPX-351 + venetoclax or azacitidine + venetoclax | 7 + 3 or CPX-351 | MRD after induction | 268 | Shami/NCI, USA, Canada (SWOG) | NCT05554406 |
| • Intermediate risk • No FLT3-ITD or -TKD | 18-59 | 7 + 3 + venetoclax or azacitidine + venetoclax | 7 + 3 + venetoclax or azacitidine + venetoclax | 7 + 3 | MRD after induction | 153 | Savoie/NCI, Canada, USA (CCTG) | NCT05554393 |
| • All comers | 18-59 | Venetoclax | Venetoclax + decitabine | 7 + 3 | ORR§ | 188 | Suning, China | NCT05177731 |
| • TP53 mut | ≥18 | Magrolimab | Magrolimab + azacitidine | Venetoclax + azacitidine or 7 + 3 | OS | 356 | Gilead, USA | NCT04778397 |
| • Adverse risk, intermediate risk, and 50-70 y • No FLT3-ITD | 18-70 | Magrolimab | Magrolimab + venetoclax + azacitidine | DA, DA + GO, CPX-351, or FLAG-Ida | EFS | 164 | Craddock, UK (NCRI) | ISRCTN71474257 |
Trials for unfit patients, children, APL, relapsed or refractory disease and with purely maintenance or conditioning questions were excluded.
CBF, core binding factor; CRi, complete hematologic remission with incomplete hematologic recovery; DA, daunorubicin plus cytarabine (ara-c); EFS, event-free survival; GO, gemtuzumab ozogamicin; LDAC, low-dose cytarabine; MRD, measurable residual disease; mut, mutation; OS, overall survival; PI, principal investigator.
sAML/tAML/HMA pretreatment not accounted for/mentioned in table. †Secondary end points for all trials include response rates, MRD, tolerability, rate of allogeneic HCT, patient-reported outcomes, and survival end points. ‡“7 + 3” stands for all variations of standard-dose cytarabine plus anthracycline/mitoxantrone and includes intensive consolidation for patients ineligible for allogeneic HCT. §ORR, overall response rate (CR+CRi+morphologic leukemia-free state MLFS).