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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00880243
• Other study ID #: ALFA 9802
• Status: Completed
• Phase: Phase 3
• First received: April 8, 2009
• Last updated: April 10, 2009
• Start date: March 1999
• Est. completion date: September 2006

Study information

• Verified date: April 2009
• Source: Acute Leukemia French Association
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 473
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 50 Years

Eligibility

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,

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Acute Leukemia French Association	Hospices Civils de Lyon

References & Publications (1)

Thomas X, Raffoux E, Botton Sd, 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-m — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No