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

NCT ID: NCT00880243

Last Updated: 2009-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 473 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-03-31
• Study Completion Date: 2006-09-30

Brief Summary

The purpose of this study is:

1. To compare priming with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) during induction and consolidation courses versus no priming.

2. To compare as consolidation timed sequential chemotherapy versus four courses of high dose cytarabine.

Detailed Description

Patients aged 15-50 are enrolled and randomly assigned to receive GM-CSF or no GM-CSF during all remission-induction and consolidation courses of chemotherapy. Induction chemotherapy consists of a timed-sequential chemotherapy including a first sequence of chemotherapy combining daunorubicin, 80 mg/m2 per day, administered IV as a short infusion over 3 days (days 1-3), and cytarabine, 500 mg/m2 per day IV as a continuous infusion over the same period. The second sequence, administered after 4-day free interval, consists of mitoxantrone, 12 mg/m2 per day, administered IV as a short infusion over 2 days (days 8 and 9), and cytarabine, 500 mg/m2/12h, administered as a 3-hour infusion for 3 days (days 8-10). Salvage therapy consists of cytarabine, 3 g/m2/12h on days 1,3,5,7, combined with amsacrine, 100mg/m2 per day on days 1 to 3. GM-CSF (Leucomax, recombinant human GM-CSF from Escherichia Coli, Schering Plough, Kenilworth,N.J., USA) is given at a dose of 5µg/kg per day, intravenously beginning at day 1 of each chemotherapy course and continuing until the last day of chemotherapy of each course.

Patients who achieve CR after induction chemotherapy or salvage therapy are randomly assigned to consolidation courses consisting of either a timed sequential chemotherapy similar to that of the ALFA-9000 trial (P2 arm) or the CALGB postremission chemotherapy (P1 arm), which includes 4 cycles of high-dose cytarabine, followed by 4 additional maintenance courses.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EMA+GM-CSF

• 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.

Group Type: EXPERIMENTAL

GM-CSF

Intervention Type: 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

EMA without GM-CSF

• 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.

Group Type: ACTIVE_COMPARATOR

GM-CSF

Intervention Type: 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

HD AraC+ GM-CSF

• 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

Group Type: EXPERIMENTAL

GM-CSF

Intervention Type: 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

HD-AraC without GM-CSF

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

Group Type: ACTIVE_COMPARATOR

GM-CSF

Intervention Type: 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

Interventions

GM-CSF

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

Intervention Type: DRUG

Other Intervention Names

GM-CSF: molgramostim; AraC: Cytarabine; Daunorubicine: Cerubidine; EMA: etoposide, mitoxantrone, cytarabine

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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,

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: collaborator

Acute Leukemia French Association

OTHER

Sponsor Role: lead

Responsible Party

Service Hematologie, LYON, France

Principal Investigators

XAVIER THOMAS, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

References

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.

Reference Type: RESULT

PMID: 17252021 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21690555 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20625116 (View on PubMed)

Other Identifiers

ALFA 9802

Identifier Type: -

Identifier Source: org_study_id