Efficacy of Gemtuzumab Ozogamycin for Patients Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk

NCT ID: NCT00860639

Last Updated: 2017-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 327 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2016-09-26

Brief Summary

The main objective of the study is to improve outcome of younger patients (between 18-60 years) with acute myeloid leukemia and intermediate risk defined by the cytogenetics. In this population, in the absence of bone marrow transplantation, event free survival (EFS) is estimated at 35% after three years of follow-up. Adjunction of gemtuzumab ozogamycin (MYLOTARG®) to standard chemotherapy is supposed to increase EFS up to 50% at 3 years. To test this hypothesis, the Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS ) sponsored by Nantes University Hospital leads this randomized open phase III trial in 29 French centers.

Detailed Description

Initial randomization will be completed upon receipt of karyotype results and will determine the administration of gemtuzumab ozogamycin (MYLOTARG ®) in combination with chemotherapy during the induction course and the first intensive consolidation course. The induction course include: Daunorubicin for 3 days (60mg/m²) associated with cytarabine (200mg/m²) for 7 days. The MYLOTARG ® will be administered according to the randomization arm on the 4th day of treatment by slow intravenous infusion of 2 hours at a dose of 6 mg/m2. Early bone marrow assessment will be performed at D15. In case of blast excess (>5%) , a second course of induction will be administered.

The consolidation treatment depends on age, molecular prognostic factors, and donor availability:

• Patients with good molecular prognosis profile [ NPM1 + / FLT3 ITD - or CEBPa mutated ] will be consolidated by two courses of intensive chemotherapy comprising Mitoxanthrone and intermediate dose of Cytarabine with or without MYLOTARG ® according to the initial randomization during the first course.
• Patients younger than 51 years, eligible for standard allogeneic transplantation with sibling or full matched unrelated donor will receive a standard bone marrow transplantation which not begin before 90 days after the induction.
• Patients with no donor or older than 50 years, or with a donor being identified, will receive two courses of intensive consolidation comprising Mitoxantrone and intermediate-dose of Cytarabine with or without Mylotarg ® 6 mg / m² during the first consolidation according to the randomisation arm.
• Patients aged 51 to 60 years with an HLA identical donor (sibling or unrelated), will receive a non-myeloablative haematopoietic stem cells transplant (HSCT) after the second course of consolidation.
• For other patients, an autologous hematopoietic stem cells transplant (HSCT) will be performed after the 2nd course of consolidation. Collection of peripheral blood stem cells (PBSCs) will be performed after the first consolidation course and a second collection may be considered after the second consolidation course in case of inadequate collection.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

gemtuzumab ozogamycin

Initial randomization will be completed upon receipt of karyotype results and will determine the administration of gemtuzumab ozogamycin (MYLOTARG ®) in combination with chemotherapy during the induction course and the first intensive consolidation course.

Group Type: ACTIVE_COMPARATOR

gemtuzumab ozogamycin

Intervention Type: DRUG

gemtuzumab ozogamycin = 6mg/m² during the induction course (Day 4) gemtuzumab ozogamycin = 6mg/m² during the first intensive consolidation course (Day 4)

without Mylotarg

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

gemtuzumab ozogamycin

gemtuzumab ozogamycin = 6mg/m² during the induction course (Day 4) gemtuzumab ozogamycin = 6mg/m² during the first intensive consolidation course (Day 4)

Intervention Type: DRUG

Other Intervention Names

gemtuzumab ozogamycin (MYLOTARG ®)

Eligibility Criteria

Inclusion Criteria

• Adult patients with de novo AML and intermediate risk as defined by the cytogenetics criteria of GOELAMS Group:

• Normal karyotype or
• Karyotype with other abnormalities, excluding the favourable group [t (15; 17), t (8; 21), inv (16)] and the high risk group [(-5/5q-, -7/7q- , t (9.22), t (6.9), 11q23 anomaly excluding the t (9; 11), abnormal 3q, complex karyotype (> 3 abnormalities)]. Not previously treated for AML.
• Patients aged 18 to 60 years
• And having more than 20% of blast cells in bone marrow and as previously described.
• And with intermediate cytogenetics as previously defined
• And whose expression of the CD33 antigen on the blasts was defined using standard method
• And with a WBC <or equal to 100G/L.
• And who can receive either one or the other of the treatments under study
• And having a good performance status (WHO score <3) with a life expectancy greater than one month.
• Affiliated with the Social Security

Exclusion Criteria

• Patients aged under 18 or over 60 years
• OR with AML:

• Not classifiable in the classification French-American-British (FAB)
• Type M3
• Or blastic transformation of a myeloproliferative or myelodysplastic syndrome previously diagnosed
• Outside the intermediate cytogenetic group as previously defined
• OR with isolated extramedullary localization of their disease
• OR WBC> 100G / L
• Patients with known human immunodeficiency virus (HIV) infection or human T-lymphotrophic virus 1 (HTLV-1)
• Patients with SGOT/SGPT >5N
• Patients with a calculated creatinine clearance of <50 mL/min
• Informed consent refusal
• Pregnant and/or lactating female

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chugai Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

French Innovative Leukemia Organisation

OTHER

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacques Delaunay, MD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

CH Pays d'Aix

Aix, , France

CHU Amiens

Amiens, , France

CHRU Angers

Angers, , France

CH Avignon

Avignon, , France

Centre Hospitalier de la Côte Basque

Bayonne, , France

CHU Hôpital Minjoz

Besançon, , France

CHU Morvan

Brest, , France

CHU Hôtel Dieu

Clermont-Ferrand, , France

CH Louis Pasteur

Colmar, , France

CHU du Bocage

Dijon, , France

CHU Michallon

Grenoble, , France

CHU Dupuytren

Limoges, , France

Institut Paoli Calmette

Marseille, , France

CH Metz Thionvile

Metz, , France

CHU Lapeyronie

Montpellier, , France

CH Muller

Mulhouse, , France

CHU Hôtel Dieu

Nantes, , France

CHU Carémeau

Nîmes, , France

CH La Source

Orléans, , France

Hopital Cochin (AP-HP)

Paris, , France

CHU du Haut Lévèque

Pessac, , France

CHU Jean Bernard - La Milétrie

Poitiers, , France

CHU Robert Debré

Reims, , France

CHU Pontchaillou

Rennes, , France

Institut de Cancérologie de la Loire

Saint-Etienne, , France

CHU Hautepierre

Strasbourg, , France

CHU Purpan

Toulouse, , France

CHU Bretonneau

Tours, , France

CHU Brabois

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

BRD/06/10-I

Identifier Type: -

Identifier Source: org_study_id