Phase 3 Study to Assess Gemtuzumab, in Combination With Standard Chemotherapy, on MRD Levels, and the Role of Glasdegib as a Post-transplant Maintenance, in Adult, 18-60 Years, With Previously Untreated de Novo Fav-interm Risk AML

AML1819

MRD driven study. Addition of gemtuzumab to conventional chemotherapy to reduce MRD of patients with favorable/intermediate-risk AML. Post-consolidation assessment of MRD. Role of a post-SCT maintenance with glasdegib.

2020-09-24

2024-04-01

2027-04-01

Recruiting

Early phase I

414

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 7 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. Exclusion Criteria: 1. Patients already treated for their AML by other chemotherapeutic agents (except for no more than 7 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 (metabolic abnormalities \> 2-2.5 times the normal upper limit) 10. Severe heart failure requiring diuretics 11. Ejection fraction \< 50% 12. Uncontrolled infections 13. Severe concomitant neurological or psychiatric diseases 14. Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of chemotherapy. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for at least 6 months following discontinuation of study drug.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 414, 'type': 'ESTIMATED'}}

2024-04-10