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

Sponsor

Acute Leukemia French Association (Other)

Overall Status

Completed

CT.gov ID

NCT00880243

Collaborator

Hospices Civils de Lyon (Other)

473

Enrollment

Arms

90.1

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: GM-CSF	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

473 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Mar 1, 1999

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Sep 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

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. [72 months]

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. [72 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,