A Randomized Study of Gemtuzumab Ozogamicin (GO) With Daunorubicine and Cytarabine in Untreated Acute Myeloid Leukemia (AML) Aged of 50-70 Years Old

• ClinicalTrials.gov Identifier: NCT00927498
• Recruitment Status: Completed
• First Posted: June 25, 2009
• Last Update Posted: July 11, 2013
• Sponsor: Acute Leukemia French Association
• Collaborator: Versailles Hospital
• Information provided by (Responsible Party): Acute Leukemia French Association

Tracking Information

• First Submitted Date: April 29, 2009
• First Posted Date: June 25, 2009
• Last Update Posted Date: July 11, 2013
• Study Start Date: December 2007
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 24, 2009): Event Free Survival (EFS) [ Time Frame: Relapse or death measured from randomization ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 24, 2009)

• CR rate [ Time Frame: CR after induction ]
• Cumulative incidence of relapse [ Time Frame: Relapse from CR ]
• Overall Survival [ Time Frame: Survival from randomization ]
• Safety of the combination Mylotarg+chemotherapy [ Time Frame: Duration of study ]
• Possible predictors of response to Mylotarg: with respect to MDR (multi drug resistance) status, cytogenetics risk groups and mutational status (FLT3, MLL, CEBPa, NPM) [ Time Frame: Duration of study ]
• Relationship between minimal residual disease measured on the expression of WT1 gene and relapse of AML. [ Time Frame: Duration of study ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Randomized Study of Gemtuzumab Ozogamicin (GO) With Daunorubicine and Cytarabine in Untreated Acute Myeloid Leukemia (AML) Aged of 50-70 Years Old
• Official Title: A Phase III Multicentric Randomized Study of the Combination of Repeated Doses of Gemtuzumab Ozogamicin (GO) With Daunorubicin and Cytarabine Versus Daunorubicin and Cytarabine in Untreated Patients With Acute Myeloid Leukemia (AML) Aged of 50-70 Years Old.
• Brief Summary: The main objective of this study is to compare conventional chemotherapy: daunorubicin and the Aracytine and this chemotherapy in combination with the monoclonal antibody used Mylotarg in divided doses.

Detailed Description

Patients with a morphologically proven diagnosis AML and both the two following criteria:

• Age > 50 years and £ 70 years.
• Not previously treated for their disease.

Randomization will be centralized by phone :

Arm A chemotherapy with daunorubicin and Aracytine or Arm B Daunorubicin and Aracytine and Mylotarg.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia

Intervention

• Drug: conventional chemotherapy (AraC + Daunorubicin),

  Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2.

  Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4.

• Drug: Mylotarg associated with conventional chemotherapy (AraC + Daunorubicin),

  Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2.

  Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4.

  Mylotarg® (GO)induction : 3 mg/m2 IV (2 hours) Days 1, 4, 7. Mylotarg® (GO) First consolidation and Second Consolidation:3 mg/m2 day 1.

Study Arms

• Active Comparator: Arm A Daunorubicin and Cytarabine

  Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2.

  Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4.

  Intervention: Drug: conventional chemotherapy (AraC + Daunorubicin),
• Experimental: Arm B Daunorubicin and Cytarabine and Mylotarg

  Daunorubicin(DNR) induction : 60 mg/m2/day IV (30 min), Days 1,2,3 Daunorubicin (DNR)first consolidation : 60 mg/m2 day 1. Daunorubicin (DNR)second consolidation : 60 mg/m2 day 1 and day 2.

  Cytarabine induction :200 mg/m2/day by continuous infusion, Days 1 to 7. Cytarabine (AraC)first and second consolidation: 1g/m2/12h days 1 to 4.

  Mylotarg® (GO)induction : 3 mg/m2 IV (2 hours) Days 1, 4, 7. Mylotarg® (GO) First consolidation and Second Consolidation:3 mg/m2 day 1.

  Intervention: Drug: Mylotarg associated with conventional chemotherapy (AraC + Daunorubicin),

Publications *

• Muresan B, Mamolo C, Cappelleri JC, Mokgokong R, Palaka A, Soikkeli F, Heeg B. Comparing cure rates for gemtuzumab ozogamicin plus standard chemotherapy vs standard chemotherapy alone in acute myeloid leukemia patients. Future Oncol. 2021 Aug;17(22):2883-2892. doi: 10.2217/fon-2020-1287. Epub 2021 Apr 16.
• Renneville A, Abdelali RB, Chevret S, Nibourel O, Cheok M, Pautas C, Dulery R, Boyer T, Cayuela JM, Hayette S, Raffoux E, Farhat H, Boissel N, Terre C, Dombret H, Castaigne S, Preudhomme C. Clinical impact of gene mutations and lesions detected by SNP-array karyotyping in acute myeloid leukemia patients in the context of gemtuzumab ozogamicin treatment: results of the ALFA-0701 trial. Oncotarget. 2014 Feb 28;5(4):916-32. doi: 10.18632/oncotarget.1536.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 24, 2009): 280
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 2013
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with a morphologically proven diagnosis AML and both the two following criteria: Age > 50 years and £ 70 years. Not previously treated for their disease.
• ECOG performance status 0 to 3
• Negative serology HIV, HBV and HBC (except post vaccination)
• Serum creatinin inf 2.5N; AST and ALT inf 2.5N; total bilirubin inf 2N
• Cardiac function determined by radionucleide or echography within normal limits.
• Negative serum pregnancy test within one week before treatment for women of child bearing potential.
• Signed informed consent.

Exclusion Criteria:

• M3-AML
• AML following previously know myeloproliferative syndrome.
• Known central nervous system involvement.
• Uncontrolled infection
• Other active malignancy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00927498
• Other Study ID Numbers: ALFA 0701
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Acute Leukemia French Association
• Original Responsible Party: Professor Castaigne Sylvie, Central Hospital, Versailles
• Current Study Sponsor: Acute Leukemia French Association
• Original Study Sponsor: Same as current
• Collaborators: Versailles Hospital

Investigators

• Principal Investigator: Castaigne Sylvie, Professor; Versailles Hospital

• PRS Account: Acute Leukemia French Association
• Verification Date: July 2013