Clinical trial NCT04168502: Gemtuzumab Chemotherapy MRD Levels; Adult Untreated, de Novo, Fav Interm Risk AML
Official title: Phase 3 Study to Assess Gemtuzumab, in Combination With Standard Chemotherapy, on MRD Levels, in Adult, 18-60 Years, With Previously Untreated de Novo Fav-interm Risk AML
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: De-novo
Favorable risk
Intermediate risk
Gemtuzumab ozogamicin
Acute Myeloid Leukemia
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2019-11-19
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: MRD driven study. Addition of gemtuzumab to conventional chemotherapy to reduce MRD of patients with favorable/intermediate-risk AML. Post-consolidation assessment of MRD.

Detailed description: Setting up a multicenter, MRD (Minimal Residual Disease)-driven study that relies on addition of gemtuzumab ozogamicin to conventional chemotherapy to reduce the pre-transplant levels of MRD of patients with favorable/intermediate-risk (according to ELN 2017) AML. Post-consolidation assessment of MRD will be exploited to establish the final risk assignment and to verify whether the delivery of a post remission therapy intensity (AuSCT, Autologous Stem Cell Transplant, vs ASCT, Allogeneic Stem Cell Transplant) of which is MRD-driven will improve the outcome in terms of anti-leukemic efficacy.

Eligibility 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 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. AML supervening after antecedent myelodysplastic syndromes ≥ 6 months duration
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.

Primary outcomes:
measure: Activity of GO in combination with chemotherapy in terms of MRD negativity achievement
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.O. - SS. Antonio e Biagio e Cesare Arrigo - SC Ematologia
city: Ancona
country: Italy
facility: Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica
city: Ascoli Piceno
country: Italy
facility: Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia
city: Avellino
country: Italy
facility: AO "San Giuseppe Moscati" - UOC Ematologia con unità di trapianto
city: Bari
country: Italy
facility: AOU Consorziale Policlinico "Aldo Moro" - UO Ematologia con trapianto
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi - UOC Ematologia
city: Caserta
country: Italy
facility: Ao Sant'Anna E San Sebastiano - Caserta - Uoc Onco Ematologia
city: Castelfranco Veneto
country: Italy
facility: U.O.C. Oncoematologia - Istituto Oncologico Veneto Irccs, Presidio Ospedaliero S. Giacomo Apostolo
city: Civitanova Marche
country: Italy
facility: Asur Marche Area Vasta 3 - Presidio Ospedaliero Civitanova Marche - Uods Ematologia
city: Cona
country: Italy
facility: Aou Arcispedale Sant'Anna - Cona (Fe) - Uoc Ematologia E Fisiopatologia Della Coagulazione
city: Cremona
country: Italy
facility: Asst Di Cremona - Ospedale Di Cremona - Uo Ematologia
city: Firenze
country: Italy
facility: Aou Careggi - Firenze - Sod Ematologia
city: Frosinone
country: Italy
facility: Asl Frosinone, Ospedale F. Spaziani - Ematologia
city: Genova
country: Italy
facility: Irccs Aou San Martino - Genova - Uo Ematologia E Trapianti
city: Latina
country: Italy
facility: Presidio Ospedaliero Nord "Santa Maria Goretti" - UOC Ematologia
city: Lecce
country: Italy
facility: ASL Le/1 P.O. Vito Fazzi - UO Ematologia
city: Mestre
country: Italy
facility: Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia
city: Milano
country: Italy
facility: Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia
city: Milano
country: Italy
facility: ISTITUTO EUROPEO DI ONCOLOGIA IRCCS - MILANO - DIVISIONE DI ONCOEMATOLOGIA 176 Milano Divisione di Onco-Ematologia Istituto Europeo
city: Modena
country: Italy
facility: Aou Di Modena - Sc Ematologia
city: Napoli
country: Italy
facility: Ao Di Rilievo Nazionale Antonio Cardarelli - Napoli - Uoc Ematologia Con Trapianto Di Midollo
city: Napoli
country: Italy
facility: Aou Federico Ii - Napoli - Uoc Ematologia
city: Orbassano
country: Italy
facility: Aou San Luigi Gonzaga - Orbassano - Scdu Ematologia Generale E Oncoematologia
city: Pagani
country: Italy
facility: Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia
city: Palermo
country: Italy
facility: Ao Ospedali Riuniti Villa Sofia Cervello - Palermo - Uo Ematologia Con Utmo
city: Palermo
country: Italy
facility: Aou Policlinico P. Giaccone - Palermo - Uo Ematologia
city: Pavia
country: Italy
facility: Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia
city: Perugia
country: Italy
facility: Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
city: Pesaro
country: Italy
facility: Ao Ospedali Riuniti Marche Nord - Ospedale San Salvatore - Pesaro - Uoc Ematologia E Centro Trapianti
city: Pescara
country: Italy
facility: Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica
city: Piacenza
country: Italy
facility: Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
city: Ravenna
country: Italy
facility: Ausl Della Romagna, Ospedale "Santa Maria Delle Croci" - Ravenna - Ematologia
city: Reggio Emilia
country: Italy
facility: Ausl Di Reggio Emilia - Arcispedale Santa Maria Nuova, Irccs - Sc Ematologia
city: Rimini
country: Italy
facility: Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia
city: Roma
country: Italy
facility: Ao Complesso Ospedaliero San Giovanni / Addolorata - Roma - Uoc Ematologia
city: Roma
country: Italy
facility: AOU Policlinico Tor Vergata- UOC Trapianto cellule staminali
city: Roma
country: Italy
facility: Aou Sant'Andrea - Roma - Uoc Ematologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri - Ifo - Istituto Regina Elena - Roma - Uosd Ematologia
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio Medico - Roma - Uoc Ematologia E Trapianto Di Cellule Staminali
city: Roma
country: Italy
facility: Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
city: San Giovanni Rotondo
country: Italy
facility: Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia
city: Sassari
country: Italy
facility: Aou Di Sassari - Cliniche Universitarie - Stabilimento Cliniche Di San Pietro - Uoc Ematologia
city: Torino
country: Italy
facility: Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2
city: Treviso
country: Italy
facility: Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Integrata Di Trieste - Sc Ematologia
city: Udine
country: Italy
facility: Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica
Study officials:
References: