This phase I/II clinical trial evaluates the safety and efficacy of the combined administration of midostaurin and gemtuzumab ozogamicin in the frame of first-line standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients displaying a cytogenetic aberration or fusion transcript in the core-binding factor (CBF) genes or FMS-like tyrosine Kinase 3 (FLT3) mutation.
Written informed consent
t(8;21)/RUNX1-RUNX1T1 or
inv(16) or t(16;16)/CBFB-MYH11 or
FLT3-ITD or
Previous antineoplastic treatment for AML other than hydroxyurea and/or cytarabine for emergency use (100-200 mg/m² per day on maximal 3 days)
Previous treatment with anthracyclines
central nervous system involvement
Isolated extramedullary AML
Parallel
MODULE: conventional chemotherapy (Cytarabine+Daunorubicin) in combination with midostaurin+GO
DrugMidostaurin (IMP) induction: 25 mg or 50 mg peroral BID, days 8 to 21 depending on assigned dose level GO (IMP) induction: 3 mg/m\^2 i.v. max 4.5 mg, on day1, or on days 1, 4, or days 1, 4, 7 depending on assigned dose level Daunorubicin (DNR, non-IMP) induction: 60 mg/m\^2/day i.v., days 1 to 3 Cytarabine (AraC, non-IMP) induction: 200 mg/m\^2/day cont. infusion, days 1 to 7
MAGNOLIA-trial: Midostaurin associated with conventional chemotherapy (AraC+DNR)+GO
DrugMidostaurin (IMP): RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles; GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only Daunorubicin (DNR, non-IMP): 60 mg/m\^2 i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles
MAGNOLIA-trial: conventional chemotherapy (AraC+DNR)+GO
DrugGO (IMP): 3 mg/m\^2 i.v. max 4.5 mg on days 1, 4, 7; 1 induction cycle only Daunorubicin (DNR, non-IMP): 60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles
MAGMA-trial:GO associated with conventional chemotherapy (AraC+DNR)+Midostaurin
DrugMidostaurin (IMP): RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21, induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles; GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only Daunorubicin (DNR, non-IMP): 60 mg/m\^2/day i.v., days 1 to 3 of induction cycles 1-2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles
MAGMA-trial: conventional chemotherapy (AraC+DNR)+Midostaurin
DrugMidostaurin (IMP): RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles Daunorubicin (DNR, non-IMP): 60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders Cytarabine (AraC, non-IMP): 200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles
Maximum tolerated dose (MTD) of midostaurin and GO combination
as measured by the number of dose limiting toxicities related to midostaurin or GO exposure.
Event Free Survival (EFS)
Time interval from date of randomization until either primary treatment failure or relapse or death, whichever occurs first.
CR/CRi rate
CR/CRi rate is defined as the proportion of patients, who achieved a morphologic complete remission or a complete remission with incomplete hematologic recovery (CR or CRi) during study participation.
Duration of remission
Duration of remission is defined as time interval from date of CR/CRi until morphologic relapse.
Cumulative incidence of relapse
Cumulative incidence of relapse is defined as the time interval from date of first CR/CRi until relapse.
Relapse-free survival
Relapse-free survival is defined as the time interval from date of first CR/CRi until either morphologic relapse or death in remission.
Click on the lead sponsor to view all of their trials.
