Gemtuzumab Chemotherapy MRD Levels; Adult Untreated, de Novo, Fav Interm Risk AML

Phase 3

Recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Gemtuzumab Ozogamicin

• Registration Number: NCT04168502
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

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.

Study Timeline

• Study First Submitted: 2019-11-11
• Study First Submitted QC: 2019-11-15
• Study First Posted: 2019-11-19
• Study Start: 2020-09-24
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08
• Primary Completion: 2025-04
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 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. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental arm	Gemtuzumab Ozogamicin	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

Primary Outcome Measures

Name	Time	Method
Activity of GO in combination with chemotherapy in terms of MRD negativity achievement	2 months	Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO

Trial Locations

Locations (48)

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

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