Effect of Priming During Induction and Consolidations in Younger Acute Myeloid Leukemia (AML)

NCT00880243 | Completed Phase 3 DMC

• 1 other identifier: ALFA 9802
• Study Type: interventional
• Target: 473
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is:

1. 1.To compare priming with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) during induction and consolidation courses versus no priming.
2. 2.To compare as consolidation timed sequential chemotherapy versus four courses of high dose cytarabine.

Conditions

Acute Myeloid Leukemia

Keywords

Acute myeloid leukemia; Priming; GM-CSF; Timed-sequential chemotherapy; Prognosis

Outcome Measures

Primary Outcomes (1)

• Assessing the potential value of the daily administration of GM-CSF during induction chemotherapy and post-induction for analyzing and comparing the arms with and without GM-CSF: EFS, % of CR, duration of remission, OS and toxicity of each treatment.

  72 months

Secondary Outcomes (1)

• Evaluate the effectiveness on DFS of a single course of consolidation using a very intensive sequential chemotherapy with mitoxantrone, AraC and etoposide feasible compared to 4 courses of high dose AraC followed of 4 courses of maintenance.

  72 months

Study Arms (4)

EMA+GM-CSF

EXPERIMENTAL

* Daunorubicine (CérubidineR) : 80 mg/m2/jour IV over 30 min from day 1 to day 3, * AraC (AracytineR) : 500 mg/m2/jour IV from day 1 to day 3, * Mitoxantrone (NovantroneR) : 12 mg/m2/jour IV over 30 min from day 8 to 9 * AraC (AracytineR) : 500 mg/m2/12h IV over 3 hours from day 8 to day10. * GM-CSF (LeucomaxR): 5 µg/kg/jour IV over 6 hours from day 1 to day 10.

Drug: GM-CSF

EMA without GM-CSF

ACTIVE COMPARATOR

* Daunorubicine (CérubidineR) : 80 mg/m2/jour IV over 30 min from day 1 to day 3, * AraC (AracytineR) : 500 mg/m2/jour IV from day 1 to day 3, * Mitoxantrone (NovantroneR) : 12 mg/m2/jour IV over 30 min from day 8 to 9 * AraC (AracytineR) : 500 mg/m2/12h IV over 3 hours from day 8 to day10.

Drug: GM-CSF

HD AraC+ GM-CSF

EXPERIMENTAL

* AraC (Aracytine) : 3 g/m2/12h IV (3 hours) on days 1, 3 , 5 * GM-CSF :5 µg/kg/d IV (6 hours) from day1 to day 5

Drug: GM-CSF

HD-AraC without GM-CSF

ACTIVE COMPARATOR

\- AraC (Aracytine) : 3 g/m2/12h IV (3 hours) on days 1, 3 , 5

Drug: GM-CSF

Interventions

GM-CSF DRUG

Randomization 1: GM-CSF (5micogram/Kg/d) versus no GM-CSF during induction chemotherapy and all consolidation courses. Randomiization 2: Consolidation high dose AraC versus consolidation EMA

Also known as: GM-CSF: molgramostim, AraC: Cytarabine, Daunorubicine: Cerubidine, EMA: etoposide, mitoxantrone, cytarabine

EMA without GM-CSF; EMA+GM-CSF; HD AraC+ GM-CSF; HD-AraC without GM-CSF

Eligibility Criteria

• Age: 15 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• A morphologically proven diagnosis of AML according to the WHO classification
• Serum creatinine \< 2N; AST and ALT \< 2.5N; total bilirubin \< 2N (unless related to the underlying disease).
• ECOG performance status 0 to 2.
• Women of child-bearing must use acceptable contraceptive methods, and must have a negative serum or urine pregnancy test within 2 weeks prior the beginning treatment on this trial.
• Must be able and willing to give written informed consent

You may not qualify if:

• Patients with M3-AML. Patient with AML following diagnosed myeloproliferation or patient with prior history of MDS known for more than 3 months. Patients with AML secondary to previous treatment with cytotoxic chemotherapy or radiotherapy (therapy-related AML).
• Patient presenting any diagnosis of uncontrolled or metastatic tumor.
• Patients with uncontrolled severe infection,

Sponsors & Collaborators

• Acute Leukemia French Association: lead
• Hospices Civils de Lyon: collaborator

Related Publications (3)

• Thomas X, Raffoux E, Botton Sd, Pautas C, Arnaud P, de Revel T, Reman O, Terre C, Corront B, Gardin C, Le QH, Quesnel B, Cordonnier C, Bourhis JH, Elhamri M, Fenaux P, Preudhomme C, Michallet M, Castaigne S, Dombret H. Effect of priming with granulocyte-macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: a trial by the Acute Leukemia French Association (ALFA) Group. Leukemia. 2007 Mar;21(3):453-61. doi: 10.1038/sj.leu.2404521. Epub 2007 Jan 25.

  PMID: 17252021 RESULT

• Thomas X, Elhamri M, Raffoux E, Renneville A, Pautas C, de Botton S, de Revel T, Reman O, Terre C, Gardin C, Chelghoum Y, Boissel N, Quesnel B, Hicheri Y, Bourhis JH, Fenaux P, Preudhomme C, Michallet M, Castaigne S, Dombret H. Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study. Blood. 2011 Aug 18;118(7):1754-62. doi: 10.1182/blood-2011-04-349258. Epub 2011 Jun 20.

  PMID: 21690555 DERIVED

• 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.

  PMID: 20625116 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Mitoxantrone; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• XAVIER THOMAS, MD, PhD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 8, 2009
• First Posted: April 13, 2009
• Study Start: March 1, 1999
• Primary Completion: September 1, 2006
• Study Completion: September 1, 2006
• Last Updated: April 13, 2009

Record last verified: 2009-04