Study to determine the efficacy of Gemtuzumab Ozogamicin, together with standard chemotherapy, on minimal residual disease levels, in adult patients with Acute Myeloid Leukemia (AML), a tumor characterized from an abnormal proliferation of blood cells present in the bone marrow in the form of immature myeloid "precursors", ie cells not yet differentiated, called blasts.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

24 Sep 2020 → ongoing

Decision date (initial)

2025-01-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pfizer · Fondazione GIMEMA Franco Mandelli Onlus

External identifiers

EU CT number

2023-510433-29-00

EudraCT number

2019-003871-20

ClinicalTrials.gov

NCT04168502

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Activity of gemtuzumab ozogamicin in combination with chemotherapy in terms of MRD negativity achievement.

Secondary objectives 9

1. Overall Survival (OS)
2. Event Free Survival (EFS)
3. Cumulative incidence of relapse (CIR)
4. Response rate after induction therapy
5. Safety: adverse events (AE) and serious AE (SAE)
6. OS, EFS, DFS and CIR in different risk groups
7. OS, EFS, DFS and CIR according to the MRD level at each evaluation step
8. Response rate, OS, EFS, DFS and CIR according to baseline characteristics
9. Quality of Life (QoL) evaluation

Conditions and MedDRA coding

Favorable-intermediate-risk Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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 14 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.
11. Women of childbearing potential with a negative serum pregnancy test within 48 hrs prior to administration of chemotherapy. Post-menopausal women with amenorrhoic for at least 12 months to be considered of non-childbearing potential. Male and female patients agreed to employ an effective barrier method of birth control throughout the study and for at least 6 months following discontinuation of study drug.

Exclusion criteria 15

1. Patients already treated for their AML by other chemotherapeutic agents (except for no more than 14 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 (see no. 7 Inclusion )
10. Severe heart failure requiring diuretics
11. Ejection fraction < 50%
12. Uncontrolled infections
13. HIV positive serology
14. Severe concomitant neurological or psychiatric diseases
15. Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO

Secondary endpoints 8

1. Overall Survival (OS) at 24 months
2. Event Free Survival (EFS) at 24 months
3. Cumulative incidence of relapse (CIR) at 24 months
4. Response rate in terms of patients who achieve CR after induction therapy
5. Safety in terms of number and type of adverse events (AE) and serious AE (SAE)
6. OS, EFS, DFS and CIR in favorable and intermediate risk groups
7. OS, EFS, DFS and CIR according to the MRD level after induction and consolidation
8. Response rate, OS, EFS, DFS and CIR according to morphology, cytogenetic and molecular baseline characteristics.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

CENTRO DATI

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

CENTRO DATI

Third parties 1

Locations

1 EU/EEA country · 67 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications