1. modified event-free survival (mEFS) (Time Frame - time interval from date of randomization until either primary treatment failure or hematologic relapse or molecular failure or death, whichever occurs first): Failure to achieve a CR/CRi/CRh after a maximum of two induction cycles in the control arm (SOC) or three induction cycles in the investigational arm (VEN+AZA), i.e. primary induction failure
Hematologic relapse after previous CR/CRi/CRh
Molecular failure, defined as either
Molecular progression, defined as confirmed ≥ 1 log10 increase of NPM1 MRD level in any two samples in a patient without prior MRD negativity or
Molecular relapse after previous MRD negativity, defined as confirmed ≥ 1 log10 between two consecutive positive samples in a patient who was previously tested as MRD negative
Death
Secondary outcome:
1. Tolerability of treatment (Time Frame - from FPFV until LPLV [4 years]): cumulative occurence of CTCAE grade 3 and grade 4 adverse events
2. Remission (CR/CRi/CRh) rate (Time Frame - from FPFV until LPLV [4 years]): CR/CRi/CRh rate is defined as the proportion of patients, who achieved a CR or CRi or CRh during study participation.
3. molecular response rate (Time Frame - from FPFV until LPLV [4 years]): Proportion of patients with absence of detectable NPM1 mutant transcripts or with detectable NPM1 mutant transcripts who do not meet any of the definitions of molceular failure during study participation.
4. molecular persistence rate (Time Frame - from FPFV until LPLV [4 years]): Proportion of patients with detectable NPM1 mutant transcripts present after four cycles of treatment with less than a 4 log10 reduction from baseline.
5. Rate of CR/CRi/CRh with MRD negativity (Time Frame - from FPFV until LPLV [4 years]): Proportion of patients, who achieved a CR or CRi or CRh with NPM1-mutant transcripts/ABL1 transcripts <0.01% during study participation.
6. early mortality (Time Frame - from FPFV until LPLV [4 years]): Early mortality is defined as death from any reason within 14, 30 and 60 days from day 1 of induction treatment.
7. Relapse-free survival (RFS) (Time Frame - from FPFV until LPLV [4 years]): Relapse-free survival is defined as the time interval from date of first CR/CRi/CRh until either morphologic or molecular relapse or death in remission.
8. Overall survival (OS) (Time Frame - from FPFV until LPLV [4 years]): Overall survival is defined as time interval from date of randomization until death from any cause.
Venetoclax plus Azacitidine: Induction cycle 1:
100 mg venetoclax p.o. on day 1; 200 mg venetoclax p.o. on day 2; 400 mg venetoclax p.o. on days 3-28; 75 mg/m^2 azacitidine s.c. on days 1-7
Induction cycles 2-3:
400 mg venetoclax p.o. on days 1-28; 75 mg/m^2 azacitidine s.c. on days 1-7
Postremission cycles 1-9:
400 mg venetoclax p.o. on days 1-28; 75 mg/m^2 azacitidine s.c. on days 1-7
standard of care chemotherapy plus gemtuzumab ozogamicin: Induction cycle 1:
200 mg/m^2 cytarabine cont inf i.v. on days 1-7; 60 mg/m^2 daunorubicin i.v. on days 3-5; 3 mg/m^2 (max 1 vial) gemtuzumab ozogamicin i.v. on days 1+4+7
Induction cycle 2 (patients not in remission, moderate or non-responders):
3000/1000 mg/m^2 cytarabine i.v. BID on days 1-3; 10 mg/m^2 mitoxantrone i.v. on days 3-5
Postremission cycles 1-3:
3000/1000 mg/m^2 cytarabine i.v. BID on days 1-3
Quelle: ClinicalTrials.gov
Sie können folgenden Inhalt einem Kollegen empfehlen:
"Venetoclax Plus Azacitidine Versus Intensive Chemotherapy for Fit Patients With Newly Diagnosed NPM1 Mutated AML"
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