Gemtuzumab Chemotherapy MRD Levels; Glasdegib Post-transplant, Adult Untreated, de Novo, Fav Interm Risk AML
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring De-novo, Favorable risk, Intermediate risk, Gemtuzumab ozogamicin, Glasdegib, Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- Signed written informed consent according to ICH/EU/GCP and national/local laws
- Patients aged between 18 and 60 years
- Patients previously untreated for their AML by other chemotherapeutic agents (except for no more than 7 days HU) or radiotherapy
- 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)
- Patients with favorable-intermediate AML according to ELN 2017 (except for FLT3-ITD/TKD positive AML)
- WHO performance status 0-3
- 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
- Left Ventricular Ejection Fraction (LVEF) ≥ 50%, as determined by echocardiogram
- Absence of severe concomitant neurological or psychiatric diseases and congestive heart failure or active uncontrolled infection
- Absence of any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and the follow-up schedule.
Exclusion Criteria:
- Patients already treated for their AML by other chemotherapeutic agents (except for no more than 7 days HU) or radiotherapy
- Acute promyelocytic leukemia
- Blast crisis of chronic myeloid leukemia
- FLT3-ITD/TKD positive AML
- AML supervening after other myeloproliferative disease ≥ 6 months duration
- AML supervening after antecedent myelodysplastic syndromes
- Therapy-related AML
- Other active or progressive malignant diseases.
- Inadequate renal or liver function (metabolic abnormalities > 2-2.5 times the normal upper limit)
- Severe heart failure requiring diuretics
- Ejection fraction < 50%
- Uncontrolled infections
- Severe concomitant neurological or psychiatric diseases
- 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.
Sites / Locations
- A.O. - SS. Antonio e Biagio e Cesare Arrigo - SC EmatologiaRecruiting
- Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica EmatologicaRecruiting
- Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc EmatologiaRecruiting
- AO "San Giuseppe Moscati" - UOC Ematologia con unità di trapiantoRecruiting
- AOU Consorziale Policlinico "Aldo Moro" - UO Ematologia con trapiantoRecruiting
- Policlinico S. Orsola - Malpighi - UOC EmatologiaRecruiting
- Ao Sant'Anna E San Sebastiano - Caserta - Uoc Onco EmatologiaRecruiting
- U.O.C. Oncoematologia - Istituto Oncologico Veneto Irccs, Presidio Ospedaliero S. Giacomo ApostoloRecruiting
- Asur Marche Area Vasta 3 - Presidio Ospedaliero Civitanova Marche - Uods EmatologiaRecruiting
- Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della CoagulazioneRecruiting
- Asst Di Cremona - Ospedale Di Cremona - Uo EmatologiaRecruiting
- Aou Careggi - Firenze - Sod EmatologiaRecruiting
- Asl Frosinone, Ospedale F. Spaziani - EmatologiaRecruiting
- Irccs Aou San Martino - Genova - Uo Ematologia E TrapiantiRecruiting
- Presidio Ospedaliero Nord "Santa Maria Goretti" - UOC EmatologiaRecruiting
- ASL Le/1 P.O. Vito Fazzi - UO EmatologiaRecruiting
- Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo EmatologiaRecruiting
- Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc EmatologiaRecruiting
- Irccs Ospedale S. Raffaele - Milano - Uo OncoematologiaRecruiting
- ISTITUTO EUROPEO DI ONCOLOGIA IRCCS - MILANO - DIVISIONE DI ONCOEMATOLOGIA 176 Milano Divisione di Onco-Ematologia Istituto EuropeoRecruiting
- Aou Di Modena - Sc EmatologiaRecruiting
- Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di MidolloRecruiting
- Aou Federico Ii - Napoli - Uoc EmatologiaRecruiting
- Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E OncoematologiaRecruiting
- Asl Salerno, Presidio Ospedaliero Tortora Pagani - EmatologiaRecruiting
- Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con UtmoRecruiting
- Aou Policlinico P. Giaccone - Palermo - Uo EmatologiaRecruiting
- Fondazione Ircss Policlinico San Matteo - Pavia - Uo EmatologiaRecruiting
- Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo OsseoRecruiting
- Ao Ospedali Riuniti Marche Nord - Ospedale San Salvatore - Pesaro - Uoc Ematologia E Centro TrapiantiRecruiting
- Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia ClinicaRecruiting
- Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro TrapiantiRecruiting
- Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - EmatologiaRecruiting
- Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc EmatologiaRecruiting
- Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo EmatologiaRecruiting
- Ao Complesso Ospedaliero San Giovanni / Addolorata - Roma - Uoc EmatologiaRecruiting
- AOU Policlinico Tor Vergata- UOC Trapianto cellule staminaliRecruiting
- Aou Sant'Andrea - Roma - Uoc EmatologiaRecruiting
- Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area EmatologicaRecruiting
- Istituti Fisioterapici Ospitalieri - Ifo - Istituto Regina Elena - Roma - Uosd EmatologiaRecruiting
- Policlinico Universitario Campus Bio Medico - Roma - Uoc Ematologia E Trapianto Di Cellule StaminaliRecruiting
- Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. EmatologiaRecruiting
- Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - EmatologiaRecruiting
- Aou Di Sassari - Cliniche Universitarie - Stabilimento Cliniche Di San Pietro - Uoc EmatologiaRecruiting
- Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2Recruiting
- Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca TrevigianaRecruiting
- Azienda Sanitaria Universitaria Integrata Di Trieste - Sc EmatologiaRecruiting
- Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica EmatologicaRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Experimental arm
Standard arm
Induction: Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7 Consolidation: Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6 Allogeneic transplantation or Autologous transplantation according to MRD level Maintenance with glasdegib 100 mg daily for one year or until toxicity/relapse
Induction: Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7 Consolidation: Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6 Allogeneic transplantation or Autologous transplantation according to MRD level clinical observation