ALFA1401: Gemtuzumab Ozogamicin+Cytarabine vs Idarubicin+Cytarabine in Elderly Patients With AML.Mylofrance 4

Sponsor

Versailles Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02473146

Collaborator

(none)

225

Enrollment

Locations

Arms

Anticipated Duration (Months)

10.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Gemtuzumab ozogamicin (GO)	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

225 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Apr 1, 2019

Anticipated Study Completion Date :

Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mylotarg Arm After randomization patients in the experimental arm are assigned to receive chemotherapy with: Gemtuzumab Ozogamicin 3 mg/m2 (maximum dose: 5 mg) per IV, 60mn on Day 1 and 4 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7	Drug: Gemtuzumab ozogamicin (GO) Other Names: Mylotarg
No Intervention: Control Arm After randomization patients in the control arm are assigned to receive chemotherapy with Idarubicin 12mg/m2 per IV, 30mn on Day 1,2,3 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7

Arm

Intervention/Treatment

Experimental: Mylotarg Arm

After randomization patients in the experimental arm are assigned to receive chemotherapy with: Gemtuzumab Ozogamicin 3 mg/m2 (maximum dose: 5 mg) per IV, 60mn on Day 1 and 4 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7

Drug: Gemtuzumab ozogamicin (GO)

Other Names:

Mylotarg

No Intervention: Control Arm

After randomization patients in the control arm are assigned to receive chemotherapy with Idarubicin 12mg/m2 per IV, 30mn on Day 1,2,3 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7

Outcome Measures

Primary Outcome Measures

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]
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.

Secondary Outcome Measures

Composite measure for Efficacy assessed by CR/Cri rates, cumulative incidence of relapse, overall survival. [5 years]
Composite measure for safety [5 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	C.H.U d'Amiens - Hôpital Sud	Amiens	France
2	Hôpital V. Dupouy	Argenteuil	France
3	CH Avicenne	Bobigny	France
4	CHU Caen	Caen	France
5	HIA Percy	Clamart	France	92140
6	Hopital Henri Mondor	Creteil	France
7	CHU Dijon	Dijon	France
8	CH Dunkerque	Dunkerque	France
9	CH Versailles	Le Chesnay	France	78157
10	Hôpital Huriez, CHU de Lille	Lille	France
11	CHU Limoges	Limoges	France
12	Hôpital de la Conception	Marseille	France	13005
13	Centre Antoine Lacassagne	Nice	France	06100
14	CHU d'Orléans	Orléans	France	45100
15	Hopital Necker	Paris	France
16	Hopital St Louis	Paris	France
17	Hôpital Saint Antoine	Paris	France
18	CHU Lyon Sud	Pierre Benite	France
19	Centre H Becquerel	Rouen	France
20	Institut de Cancérologie de la Loire	Saint-Priest-en-Jarez	France	42270
21	IGR	Villejuif	France