Treatment of Acute Myeloid Leukemia (AML) in Adults 50 to 70 Years, Study of Two Anthracyclines and the Interest of Maintenance Treatment With Interleukin 2 (ALFA 9801)

Treatment of AML in Adults 50 to 70 Years, Study of Two Anthracyclines and the Interest of Maintenance Treatment With Interleukin 26- ALFA 9801

Randomized comparison of standard induction treatment with daunorubicin for 3 days and Idarubicin for 3 or 4 days in adult AML patients between 50 and 70 years. Study of maintenance treatment with IL2

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: chemotherapy (Aracytine + Daunorubicin); Drug: chemotherapy (Aracytine + Daunorubicin); Drug: chemotherapy (Aracytine + Daunorubicin)

Detailed Description

Patients from 50 to 70 years with de novo AML were randomized to receive ARAC 200 mg / m² / d IV x 7 d with either DNR 80 mg/m²/dx3d (arm 1) or IDA 12 mg / m²/d x 3 d (arm 2) or 4 d (arm 3). The pts received a failing course of remedial Mitoxantrone involving x 2 and j ARAC 1g / m 2 x / d x 4 days The pts in CR then received 2 courses of consolidation with, according to initial randomization either DNR 80 mg / m² IDA 12 mg / sqm x 1 d (1st treatment) or 2 d (2nd treatment) and ARAC 1 gsm 2/jx x 4 days The pts in CR were then randomized persistent IL2 (5 million IU / m² x 5 d / month in SC for 12 months) or no treatment.

• Study Type: Interventional
• Enrollment: 420
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Caen, France, 14033
    • CH
  • Clamart, France, 92141
    • Hôpital Percy
  • Creteil, France, 94010
    • CHU
  • Lens, France, 62307
    • CH
  • Lille, France, 59037
    • CHU
  • Limoges, France, 87042
    • CH
  • Lyon, France
    • Hôpital Edouard Herriot
  • Paris, France
    • Hôpital Saint-Louis
  • Paris, France, 75651
    • Hôpital Pitié-Salpétrière
  • Paris, France, 75012
    • St Antoine Hospital
  • Roubaix, France, 59100
    • CH
  • Rouen, France, 76038
    • CHU
  • Saint-Cloud, France, 92210
    • CNLCC
  • Valenciennes, France, 59322
    • CH
  • Versailles, France
    • CH
  • Villejuif, France, 94805
    • IGR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient from 50 to 70 years
• AML de Novo
• No prior therapy for AML
• Absence of severe infection (WHO grade greater than 2), independent of the AML
• Cardiac function determined by radionucleotide or echography within normal limits.
• total bilirubin less than or equal 2N and Serum creatinin less than or equal 2N
• ECOG performance status 0 to 3
• Signed informed consent.

Exclusion Criteria:

• M3-AML
• history of neoplasia treated by radiotherapy or chemotherapy
• Myelodysplasia diagnosed more than 6 months before the diagnosis of AML
• Prior treatment for AML
• Uncontrolled infection
• Other active malignancy
• Patient unable to undergo regular surveillance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm1 = Aracytine + Daunorubicin; Aracytine : 200 mg/m2 d1-d7 Daunorubicin : 80 mg/m2 d1-d3	Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Daunorubicin : 80 mg/m2 d1-d3; Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Idarubicin :12 mg/m2 d1-d3; Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Idarubicin : 12 mg/m2 d1-d4
Active Comparator: Arm 3 = Aracytine And Idarubicin; Aracytine : 200 mg/m2 d1-d7 Idarubicin : 12 mg/m2 d1-d4	Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Daunorubicin : 80 mg/m2 d1-d3; Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Idarubicin :12 mg/m2 d1-d3; Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Idarubicin : 12 mg/m2 d1-d4
Active Comparator: Arm 2 = Aracytine And Idarubicin; Aracytine : 200 mg/m2 d1-d7 Idarubicin :12 mg/m2 d1-d3	Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Daunorubicin : 80 mg/m2 d1-d3; Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Idarubicin :12 mg/m2 d1-d3; Drug: chemotherapy (Aracytine + Daunorubicin); Aracytine : 200 mg/m2 d1-d7 Idarubicin : 12 mg/m2 d1-d4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To compare idarubicin versus daunorubicin: the duration of the event-free survival (EFS) to compare IL2 versus abstention : the relapse rate assessed during the first year following the start of maintenance treatment with interleukin

Secondary Outcome Measures

Outcome Measure
Frequency and severity of adverse events

Collaborators and Investigators

• Sponsor: Acute Leukemia French Association
• Collaborators: Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Sarkozy C, Gardin C, Gachard N, Merabet F, Turlure P, Malfuson JV, Pautas C, Micol JB, Thomas X, Quesnel B, Celli-Lebras K, Preudhomme C, Terre C, Fenaux P, Chevret S, Castaigne S, Dombret H. Outcome of older patients with acute myeloid leukemia in first relapse. Am J Hematol. 2013 Sep;88(9):758-64. doi: 10.1002/ajh.23498. Epub 2013 Aug 7.
• Gardin C, Chevret S, Pautas C, Turlure P, Raffoux E, Thomas X, Quesnel B, de Revel T, de Botton S, Gachard N, Renneville A, Boissel N, Preudhomme C, Terre C, Fenaux P, Bordessoule D, Celli-Lebras K, Castaigne S, Dombret H. Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older. J Clin Oncol. 2013 Jan 20;31(3):321-7. doi: 10.1200/JCO.2011.40.3642. Epub 2012 Dec 17.
• Itzykson R, Gardin C, Pautas C, Thomas X, Turlure P, Raffoux E, Terre C, Fenaux P, Castaigne S, Dombret H, Boissel N; Acute Leukemia French Association (ALFA). Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria. Haematologica. 2011 Jun;96(6):837-44. doi: 10.3324/haematol.2010.036921. Epub 2011 Apr 1.
• Boissel N, Nibourel O, Renneville A, Gardin C, Reman O, Contentin N, Bordessoule D, Pautas C, de Revel T, Quesnel B, Huchette P, Philippe N, Geffroy S, Terre C, Thomas X, Castaigne S, Dombret H, Preudhomme C. Prognostic impact of isocitrate dehydrogenase enzyme isoforms 1 and 2 mutations in acute myeloid leukemia: a study by the Acute Leukemia French Association group. J Clin Oncol. 2010 Aug 10;28(23):3717-23. doi: 10.1200/JCO.2010.28.2285. Epub 2010 Jul 12.

Study record dates

Study Major Dates

• Study Start: December 1, 1999
• Study Completion: December 1, 2006

Study Registration Dates

• First Submitted: June 29, 2009
• First Submitted That Met QC Criteria: June 30, 2009
• First Posted (Estimate): July 2, 2009

Study Record Updates

• Last Update Posted (Estimate): July 2, 2009
• Last Update Submitted That Met QC Criteria: June 30, 2009
• Last Verified: August 1, 1999

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia in adults; Newly-diagnosed untreated AML; Patient aged 50 to 70 years
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin
• Other Study ID Numbers: ALFA 9801