Acute Myeloid Leukemia
Conditions
Keywords
Fludarabine, AML, elderly patients
Brief summary
In this study, patients were randomly assigned to either receive fludarabine or not (20 mg/m2/d) in addition to induction chemotherapy, consolidation chemotherapy and the 3 subsequent re-induction courses during maintenance.
Detailed description
Eligibility for enrollment in the study was limited to patients aged 60 to 75 years old with previously untreated de novo AML as defined morphologically by the French-American-British (FAB) classification with the exception of M3 and M7 subtypes.10,11 The bone marrow aspirate had to show at least 30 percent of nonerythroid blast cells. Patients were not eligible if they had a performance status before diagnosis of 2 or more according to the World Health Organization (WHO) grading system, congestive heart failure or abnormal left ventricular ejection fraction, severe hepatic or renal disturbances if not related to leukemia (hepatic enzymes levels over four times the normal values, serum bilirubin over 35 micromol/L, creatinine over 150 micromol/L). Patients with previous unexplained cytopenia were eligible for the study. Conversely, patients with a history of documented myelodysplastic or myeloproliferative syndrome or previously treated with chemotherapy or radiation could not enter the study. The study received in June 1996 approval from the ethics' board of the Nancy Hospital and written informed consent was given by all eligible patients before entering the study, in accordance with the Declaration of Helsinki. The enrollment period was open from November 1996 to April 2000.
Interventions
DRUGActive comparator (no fludarabine)
1. Ara-C (100 mg/m2/d by continuous IV infusion 7 days), idarubicin (8 mg/m2/d (IV) for 5 days), GM-CSF a dose of 5 mg/kg/d on day 1. (Novartis Laboratory, Rueil-Malmaison, France). 2. The consolidation course: intermediate-dose Ara-C (1g/m2 g 3-hour infusion twice a day 1 through 3) and idarubicin (10 mg/m2 on days 4 through 5). In the allocated arm 3. Maintenance therapy for one year with 6-thioguanine (100 mg/m2/d orally on days 1 through 4 every week, Ara-C (60 mg/m2 SC on day 5 weekly) interrupted every 3 months with a reinduction course including CCNU (40 mg orally on day 1), mitoguazone (350 mg/m2 on day 1) and Ara-C (40 mg/m2 sc twice daily day 1 to 5)
DRUGExperimental (fludarabine)
The same regimen with addition of fludarabine in every treatment sequence 1. Induction course: Fludarabine (20 mg/m2/d, IV for 30 minutes) was started in the assigned group on day 2 and continued until the end of cytarabine treatment on day 7. 2. Consolidation course: In the allocated arm, fludarabine (20 mg/m2/d, IV) was administered on days 2 through 3, 4 hours prior to cytarabine infusion. 3. Reinduction courses: Ara-C associated in the allocated group with fludarabine (20 mg/m2/d, IV) on days 1 through 2.
Sponsors
Schering SA
Novartis
French Innovative Leukemia Organisation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* patients aged 60 to 75 years old * untreated de novo AML * performance status less than 2
Exclusion criteria
* performance status more than 2 * congestive heart failure or abnormal left ventricular ejection fraction * severe hepatic or renal disturbances * history of documented myelodysplastic or myeloproliferative syndrome * patients previously treated with chemotherapy or radiation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival (EFS) | long term results (median follow up: 71 months) |
Secondary
| Measure | Time frame |
|---|---|
| evaluation of the CR rate, remission duration disease-free survival (DFS) overall survival (OS), | long term results (median follow up: 71 months) |
Countries
France
Outcome results
None listed