Efficacy of Gemtuzumab Ozogamycin for Patients Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk (LAM2006IR)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Chugai Pharmaceutical
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Information provided by:
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT00860639
First received: March 11, 2009
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: gemtuzumab ozogamycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Open Phase III Trial Testing Efficacy of Gemtuzumab Ozogamycin (MYLOTARG) Associated to Intensive Chemotherapy for Patients Aged Between 18-60 Years and Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • event free survival (EFS)after 3 years for patients not eligible for standard allogenic transplantation [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete Remission Rate (CR) Overall Survival at 3 years Relapse rate at 3 years Toxicity and tolerability of each treatment arm Evaluation of Minimal residual disease by WT1 and NPM1 study at different phases of treatment. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 327
Study Start Date: October 2007
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: gemtuzumab ozogamycin
gemtuzumab ozogamycin = 6mg/m² during the induction course (Day 4) gemtuzumab ozogamycin = 6mg/m² during the first intensive consolidation course (Day 4)
Other Name: gemtuzumab ozogamycin (MYLOTARG ®)
No Intervention: without Mylotarg

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.
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860639

Locations
France
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
Besancon, France
CH Blois
Blois, 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
Clinique du Parc
Montpellier, France
CH Muller
Mulhouse, France
CHU Hôtel Dieu
Nantes, France
CHU Archet 1
Nice, France
CHU Carémeau
Nimes, France
CH La Source
Orléans, France
Hopital Cochin (AP-HP)
Paris, France
Centre Hospitalier Saint-Jean
Perpignan, 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
Vandoeuvre Les Nancy, France
Sponsors and Collaborators
Nantes University Hospital
Chugai Pharmaceutical
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Investigators
Principal Investigator: Jacques Delaunay, MD Nantes University Hospital
  More Information

No publications provided

Responsible Party: General Director, Nantes University Hospital
ClinicalTrials.gov Identifier: NCT00860639     History of Changes
Other Study ID Numbers: BRD 06/10-I
Study First Received: March 11, 2009
Last Updated: January 7, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Nantes University Hospital:
AML
gemtuzumab ozogamycin

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Gemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014