Clinical trial NCT02473146: Gemtuzumab Ozogamicin+Cytarabine vs Idarubicin+Cytarabine in Elderly Patients With AML.Mylofrance 4
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: AML
untreated
60-80 years old
favorable and intermediate karyotype
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2015-06-16
Enrollment: 225
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 5 years
Secondary outcomes:
measure: Composite measure for Efficacy assessed by CR/Cri rates, cumulative incidence of relapse, overall survival.
timeFrame: 5 years
measure: Composite measure for safety
timeFrame: 5 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: C.H.U d'Amiens - Hôpital Sud
city: Argenteuil
country: France
facility: Hôpital V. Dupouy
city: Bobigny
country: France
facility: CH Avicenne
city: Caen
country: France
facility: CHU Caen
city: Clamart
country: France
facility: HIA Percy
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon
city: Dunkerque
country: France
facility: CH Dunkerque
city: Le Chesnay
country: France
facility: CH Versailles
city: Lille
country: France
facility: Hôpital Huriez, CHU de Lille
city: Limoges
country: France
facility: CHU Limoges
city: Marseille
country: France
facility: Hôpital de la Conception
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: CHU d'Orléans
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopital St Louis
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Pierre Benite
country: France
facility: CHU Lyon Sud
city: Rouen
country: France
facility: Centre H Becquerel
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Villejuif
country: France
facility: IGR
Study officials:
affiliation: Versailles Hospital
name: Juliette LAMBERT, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Versailles Hospital
name: Sylvie CASTAIGNE, MD
role: PRINCIPAL_INVESTIGATOR
References: