Effect of Priming During Induction and Consolidations in Younger Acute Myeloid Leukemia (AML) - Full Text View

Purpose

The purpose of this study is:

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

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: GM-CSF	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Effect of Priming With Granulocyte-Macrophage Colony-Stimulating Factor During Chemotherapy and Comparison of Timed Sequential Chemotherapy vs 4 Courses of High Dose Cytarabine as Consolidation in Younger Adults With Newly Diagnosed AML

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Cytarabine Mitoxantrone Mitoxantrone hydrochloride Sargramostim

U.S. FDA Resources

Further study details as provided by Acute Leukemia French Association:

Primary Outcome Measures:

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. [ Time Frame: 72 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: 72 months ] [ Designated as safety issue: No ]

Enrollment:	473
Study Start Date:	March 1999
Study Completion Date:	September 2006
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: 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 Other Names: GM-CSF: molgramostim AraC: Cytarabine Daunorubicine: Cerubidine EMA: etoposide, mitoxantrone, cytarabine
Active Comparator: 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.	Drug: 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 Other Names: GM-CSF: molgramostim AraC: Cytarabine Daunorubicine: Cerubidine EMA: etoposide, mitoxantrone, cytarabine
Experimental: 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	Drug: 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 Other Names: GM-CSF: molgramostim AraC: Cytarabine Daunorubicine: Cerubidine EMA: etoposide, mitoxantrone, cytarabine
Active Comparator: HD-AraC without GM-CSF - AraC (Aracytine) : 3 g/m2/12h IV (3 hours) on days 1, 3 , 5	Drug: 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 Other Names: GM-CSF: molgramostim AraC: Cytarabine Daunorubicine: Cerubidine EMA: etoposide, mitoxantrone, 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.

Eligibility

Ages Eligible for Study:	15 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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,

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00880243

Sponsors and Collaborators

Acute Leukemia French Association

Hospices Civils de Lyon

Investigators

Principal Investigator:

XAVIER THOMAS, MD, PhD

Hospices Civils de Lyon

More Information

Publications:

Thomas X, Raffoux E, Botton S, Pautas C, Arnaud P, de Revel T, Reman O, Terré 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. Epub 2007 Jan 25.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Thomas X, Elhamri M, Raffoux E, Renneville A, Pautas C, de Botton S, de Revel T, Reman O, Terré 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. Epub 2011 Jun 20.

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. Epub 2010 Jul 12.

Responsible Party:	Xavier THOMAS, MD, PhD, Service Hematologie, LYON, France
ClinicalTrials.gov Identifier:	NCT00880243 History of Changes
Other Study ID Numbers:	ALFA 9802
Study First Received:	April 8, 2009
Last Updated:	April 10, 2009
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: Institutional Ethical Committee

Keywords provided by Acute Leukemia French Association:

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

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Molgramostim
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on June 18, 2013