Favorable-intermediate-risk Acute Myeloid Leukemia (AML) MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: MYLOTARG 5 mg polvere per concentrato per soluzione per infusione
Product Name: Gemtuzumab Ozogamicin
Product Code: [NA]
Pharmaceutical Form: Powder for solution for infusion
INN or Propos
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Signed written informed consent according to ICH/EU/GCP and national/local laws 2 Patients aged between 18 and 60 years 3 Patients previously untreated for their AML by other chemotherapeutic agents (except for no more than 14 days HU) or radiotherapy 4 Unequivocal diagnosis of de novo AML according to WHO diagnostic criteria (at least 20% blasts in the bone marrow), other than acute promyelocytic leukemia, documented by bone marrow aspiration (or biopsy in case of dry tap) (not supervening after other myeloproliferative disease or myelodysplastic syndromes of = 6 months duration) 5 Patients with favorable-intermediate AML according to ELN 2017 (except for FLT3-ITD/TKD positive AML) 6 WHO performance status 0-3 7 Adequate renal (serum creatinine = 2 x the institutional ULN) and liver (total serum bilirubin = 2 x ULN; serum ALT and AST = 2.5 x ULN) function, unless considered due to organ leukemic involvement 8 Left Ventricular Ejection Fraction (LVEF) = 50%, as determined by echocardiogram 9 Absence of severe concomitant neurological or psychiatric diseases and congestive heart failure or active uncontrolled infection 10 Absence of any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and the follow-up schedule. 11 Women of childbearing potential with a negative serum pregnancy test within 48 hrs prior to administration of chemotherapy. Post-menopausal women with amenorrhoic for at least 12 months to be considered of non-childbearing potential. Male and female patients agreed to employ an effective barrier method of birth control throughout the study and for at least 6 months following discontinuation of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 414 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients already treated for their AML by other chemotherapeutic agents (except for no more than 14 days HU) or radiotherapy 2. Acute promyelocytic leukemia 3. Blast crisis of chronic myeloid leukemia 4. FLT3-ITD/TKD positive AML 5. AML supervening after other myeloproliferative disease = 6 months duration 6. AML supervening after antecedent myelodysplastic syndromes 7. Therapy-related AML 8. Other active or progressive malignant diseases. 9. Inadequate renal or liver function (see no. 7 Inclusion ) 10. Severe heart failure requiring diuretics 11. Ejection fraction < 50% 12. Uncontrolled infections 13. HIV positive serology 14. Severe concomitant neurological or psychiatric diseases 15. Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study has two co-primary objectives: 1.Activity of gemtuzumab ozogamicin in combination with chemotherapy in terms of MRD negativity achievement; 2.Efficacy of glasdegib maintenance vs clinical observation;Secondary Objective: To assess: 1.Overall Survival (OS) 2.Event Free Survival (EFS) 3.Cumulative incidence of relapse (CIR) 4.Response rate after induction therapy 5.Safety: adverse events (AE) and serious AE (SAE) 6.OS, EFS, DFS and CIR in different risk groups 7.OS, EFS, DFS and CIR according to the MRD level at each evaluation step 8.Response rate, OS, EFS, DFS and CIR according to baseline characteristics 9.Quality of Life (QoL) evaluation;Primary end point(s): Co-Primary 1.Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO; 2.Disease Free Survival (DFS) in patients randomized to glasdegib maintenance or clinical observation;Timepoint(s) of evaluation of this end point: 1. After the consolidation phase for patients treated with Gemtuzumab Ozogamicin during the induction and consolidation phases. 2. At the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary study end-points are: 1. Overall Survival (OS) at 24 months 2. Event Free Survival (EFS) at 24 months 3. Cumulative incidence of relapse (CIR) at 24 months 4. Response rate in terms of patients who achieve CR after induction therapy 5. Safety in terms of number and type of adverse events (AE) and serious AE (SAE) 6. OS, EFS, DFS and CIR in favorable and intermediate risk groups 7. OS, EFS, DFS and CIR according to the MRD level after induction and consolidation 8. Response rate, OS, EFS, DFS and CIR according to morphology, cytogenetic and molecular baseline characteristics. 9. To estimate mean trajectories over time of pre-selected QoL scales of the EORTC QLQ-C30 questionnaire.;Timepoint(s) of evaluation of this end point: 1. 24 months after starting the study; 2. 24 months after starting the study; 3. 24 months after obtaining the remission; 4. After induction therapy; 5. During the entire course of the study; 6. 24 months after starting the study; 7. 24 months after starting the study; 8. 24 months after starting the study; 9. From the baseline to the end of the study. | — |
Countries
Italy
Contacts
Public ContactCentro Dati GIMEMA
Fondazione GIMEMA
Outcome results
None listed