Gemtuzumab Chemotherapy MRD Levels; Glasdegib Post-transplant, Adult Untreated, de Novo, Fav Interm Risk AML

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04168502
• Other study ID #: AML1819
• Status: Recruiting
• Phase: Phase 3
• Start date: September 24, 2020
• Est. completion date: April 2027

Study information

• Verified date: April 2024
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: Paola Fazi
• Phone: 0670390528
• Email: p.fazi[@]gimema.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. Role of a post-SCT maintenance with glasdegib.

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. Finally, the role of a post-SCT maintenance with glasdegib will be explored.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 414
• Est. completion date: April 2027
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Glasdegib
After randomization patients in both arms will be randomized to maintenance with glasdegib vs clinical observation
• Gemtuzumab Ozogamicin
Both arms, before randomization, will receive induction and consolidation with Gemtuzumab ozogamicin, Daunorubicin and Cytarabine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Activity of GO in combination with chemotherapy in terms of MRD negativity achievement	Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO	2 months
Primary	Efficacy of Glasdegib maintenance vs clinical observation	Disease Free Survival (DFS) in patients randomized to glasdegib maintenance or clinical observation	2,5 years