Gemtuzumab Ozogamicin+Cytarabine vs Idarubicin+Cytarabine in Elderly Patients With AML.Mylofrance 4

Acute Myeloid Leukemia Clinical Trial

— ALFA1401  

Official title:

Etude Exploratoire randomisée Comparant le Traitement Par Gemtuzumab Ozogamicin /Cytarabine au Traitement Standard Par Idarubicine/Cytarabinechez Les Sujets âgés de 60 à 80 Ans et présentant Une LAM et un Caryotype Non défavorable

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02473146
• Other study ID #: 2014-001395-65
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 18, 2015
• Est. completion date: September 7, 2023

Study information

• Verified date: February 2024
• Source: Versailles Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose : The main objective of this study is to assess the efficacy and tolerance of the addition of repeated doses of low doses (3mg/m2) of Gemtuzumab Ozogamicin (GO) in addition with standard doses of Ara-C in previously untreated patients aged 60 to 80 years with de novo acute myeloblastic leukemia (AML) and non adverse cytogenetics. The main end point for efficacy is 2 years-event free survival. The secondary efficacy endpoints are CR/Cri rates, cumulative incidence of relapse and overall survival. The secondary endpoints for safety are early death rate (before day 30 and 60), grade 3 to 5 adverse events and severe adverse events, cardiac toxicity and quality of life. Additional secondary endpoints are treatment by covariate interactions with respect to biological characteristics present at diagnosis (CD33 positivity, cytogenetic, molecular abnormalities) or after treatment (Minimal residual disease levels). This study is an exploratory study. Patients will be allocated at inclusion with a 2/1 ratio either to receive treatment with GO and cytarabine or Idarubicin and cytarabine in a 3+7 regimen similar to the "backbone" ALFA 1200 scheme used concurrently by the ALFA group as treatment of AML patients aged >60 years.

Primary objective. The primary objective is to assess the efficacy of two doses of Gemtuzumab ozogamicin (GO) during induction and one dose of GO during first consolidation in combination with Cytarabine in elderly patients with AML in the non adverse cytogenetics-risk group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: September 7, 2023
• Est. primary completion date: February 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients with a morphologically proven diagnosis AML and both the following criteria:

• Age = 60 years and < 80 years.

• Not previously treated for their disease.

• With favourable or intermediate-risk cytogenetics. (Patients with urgent clinical need to begin treatment might be included before cytogenetic results, when necessary if they do not respond to Hydroxyurea. Patients might be included if the cytogenetic results are not expected in a time limit < 5 days after AML diagnosis).

• Fit to receive intensive chemotherapy

• Cardiac function determined by radionucleide or echography within normal limits.

• Signed informed consent

Exclusion Criteria:

• M3-AML

• Presence of adverse cytogenetics (according to European LeukemiaNet recommendation.) (17) defined as one of the following abnormalities: -5/5q-, -7, t(6;9), t(v;11q23) excluding t(9;11), inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), complex karyotype (3+ abnormalities)

• Secondary AML following treatment with radiotherapy or chemotherapy.

• AML following previously known myeloproliferative or myelodysplastic syndrome.

• ECOG performance status (PS) 0 to 3

• Serum creatinin level > or = 2.5N; AST and ALT level > or = 2.5N; total bilirubin level > or = 2N

Related Conditions & MeSH terms

• Acute Myeloid Leukemia

Intervention

Drug:
• Gemtuzumab ozogamicin (GO)

Locations

Country	Name	City	State
France	C.H.U d'Amiens - Hôpital Sud	Amiens
France	Hôpital V. Dupouy	Argenteuil
France	CH Avicenne	Bobigny
France	CHU Caen	Caen
France	HIA Percy	Clamart
France	Hopital Henri Mondor	Creteil
France	CHU Dijon	Dijon
France	CH Dunkerque	Dunkerque
France	CH Versailles	Le Chesnay
France	Hôpital Huriez, CHU de Lille	Lille
France	CHU Limoges	Limoges
France	Hôpital de la Conception	Marseille
France	Centre Antoine Lacassagne	Nice
France	CHU d'Orléans	Orléans
France	Hopital Necker	Paris
France	Hôpital Saint Antoine	Paris
France	Hopital St Louis	Paris
France	CHU Lyon Sud	Pierre Benite
France	Centre H Becquerel	Rouen
France	Institut de Cancérologie de la Loire	Saint-Priest-en-Jarez
France	IGR	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Versailles Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EFS (defined as the time from randomization to the date of assessment of response if CR or Cri had not been achieved, relapse or death)	Endoint for the primary objective of efficacy is EFS defined as the time from randomization to the date of assessment of response if CR or Cri had not been achieved, relapse or death.	5 years
Secondary	Composite measure for Efficacy assessed by CR/Cri rates, cumulative incidence of relapse, overall survival.		5 years
Secondary	Composite measure for safety	incidence of early deaths < day 30 and day 60,; grade 3 to 5 adverse events and all serious adverse events during induction and consolidation treatment; cardiac toxicity evaluated on cardiac ejection function evaluation by echocardiography or isotopic measure.; Quality of life measured by questionaries' EORTC QLQ-C30 repeated at diagnosis, after induction treatment, after the two consolidations and 3 months after the end of treatment.; End points for treatment-by-covariate interactions are; at diagnosis: percentage of CD33 positivity on blast cells, measured with a standardized method, cytogenetics and most relevant molecular markers (FLT3, MLL, CEBPa, NPM1, DNMT3a.,; after induction and end of treatment: minimal residual disease determined by WT1 and/or NPM1 transcripts levels.	5 years