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

January 26, 2017 updated by: Nantes University Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

327

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Aix, France
        • CH Pays d'Aix
      • Amiens, France
        • CHU Amiens
      • Angers, France
        • CHRU Angers
      • Avignon, France
        • Ch Avignon
      • Bayonne, France
        • Centre Hospitalier de la Cote Basque
      • Besancon, France
        • CHU Hôpital Minjoz
      • Brest, France
        • CHU Morvan
      • Clermont-Ferrand, France
        • Chu Hotel Dieu
      • Colmar, France
        • CH Louis Pasteur
      • Dijon, France
        • Chu Du Bocage
      • Grenoble, France
        • CHU Michallon
      • Limoges, France
        • Chu Dupuytren
      • Marseille, France
        • Institut Paoli Calmette
      • Metz, France
        • CH Metz Thionvile
      • Montpellier, France
        • CHU Lapeyronie
      • Mulhouse, France
        • CH Muller
      • Nantes, France
        • Chu Hotel Dieu
      • Nimes, France
        • CHU Caremeau
      • Orléans, France
        • CH La Source
      • Paris, France
        • Hôpital Cochin (AP-HP)
      • Pessac, France
        • CHU du Haut Leveque
      • Poitiers, France
        • CHU Jean Bernard - La Milétrie
      • Reims, France
        • CHU Robert Debré
      • Rennes, France
        • Chu Pontchaillou
      • Saint Etienne, France
        • Institut de Cancerologie de La Loire
      • Strasbourg, France
        • CHU Hautepierre
      • Toulouse, France
        • CHU Purpan
      • Tours, France
        • Chu Bretonneau
      • Vandoeuvre Les Nancy, France
        • CHU Brabois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • gemtuzumab ozogamycin (MYLOTARG ®)
No Intervention: without Mylotarg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
event free survival (EFS)after 3 years for patients not eligible for standard allogenic transplantation
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Collaborators

Chugai Pharmaceutical
French Innovative Leukemia Organisation

Investigators

  • Principal Investigator: Jacques Delaunay, MD, Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

September 26, 2016

Study Completion (Actual)

September 26, 2016

Study Registration Dates

First Submitted

March 11, 2009

First Submitted That Met QC Criteria

March 11, 2009

First Posted (Estimate)

March 12, 2009

Study Record Updates

Last Update Posted (Estimate)

January 27, 2017

Last Update Submitted That Met QC Criteria

January 26, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRD/06/10-I

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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