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

Acute Leukemia French Association

Status and phase

Completed

Phase 3

Conditions

Acute Myeloid Leukemia

Treatments

Drug: GM-CSF

Study type

Interventional

Funder types

Other

Identifiers

NCT00880243

ALFA 9802

Details and patient eligibility

About

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.

Full 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.

Enrollment

473 patients

Sex

All

Ages

15 to 50 years old

Volunteers

No 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,

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

473 participants in 4 patient groups

EMA+GM-CSF

Experimental group

Description:

* 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.

Treatment:

Drug: GM-CSF

EMA without GM-CSF

Active Comparator group

Description:

Treatment:

Drug: GM-CSF

HD AraC+ GM-CSF

Experimental group

Description:

* 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

Treatment: