GOELAMS SA4 Study: the Role of Fludarabine in the Treatment of Acute Myeloid Leukemia in the Elderly

Sponsor

French Innovative Leukemia Organisation (Other)

Overall Status

Completed

CT.gov ID

NCT00925873

Collaborator

Schering SA (Other), Novartis (Industry)

303

Enrollment

Location

Arms

101

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Active comparator (no fludarabine) Drug: Experimental (fludarabine)	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

303 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Study of Fludarabine in Part of Induction and Postremission Treatment for de Novo Acute Myeloid Leukaemia in Elderly Patients

Study Start Date :

Jun 1, 1996

Actual Primary Completion Date :

Apr 1, 2000

Actual Study Completion Date :

Nov 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Control arm without fludarabine Induction course: Ara-C 100mg/m2 days 1-7, idarubicin 8mg/m2 days 1-5, GM-CSF (molgramostim, Novartis) 5 microg/kg days 1 to neutrophil recovery; Consolidation course: Ara-C 1g/m2 q12h days 1-3, idarubicin 10mg/m2 days 2-3; and 3 quarterly reinduction courses during maintenance including Ara-C 80mg/m2 days 1-5, CCNU 40mg and mitoguazone 350mg/m2 day 1, ± fludarabine days 1-2.	Drug: Active comparator (no fludarabine) 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). 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 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) Other Names: Arm A
Experimental: 2 Fludarabine arm The same regimen with fludarabine 20 mg/m2/day IV for 30 minutes induction course + fludarabine days 2-7; consolidation course + fludarabine days 4-5; during reinduction courses + fludarabine days 1-2.	Drug: Experimental (fludarabine) The same regimen with addition of fludarabine in every treatment sequence 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. 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. Reinduction courses: Ara-C associated in the allocated group with fludarabine (20 mg/m2/d, IV) on days 1 through 2. Other Names: Arm B

Arm

Intervention/Treatment

Active Comparator: 1

Control arm without fludarabine Induction course: Ara-C 100mg/m2 days 1-7, idarubicin 8mg/m2 days 1-5, GM-CSF (molgramostim, Novartis) 5 microg/kg days 1 to neutrophil recovery; Consolidation course: Ara-C 1g/m2 q12h days 1-3, idarubicin 10mg/m2 days 2-3; and 3 quarterly reinduction courses during maintenance including Ara-C 80mg/m2 days 1-5, CCNU 40mg and mitoguazone 350mg/m2 day 1, ± fludarabine days 1-2.

Drug: Active comparator (no fludarabine)

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). 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 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)

Other Names:

Arm A

Experimental: 2

Fludarabine arm The same regimen with fludarabine 20 mg/m2/day IV for 30 minutes induction course + fludarabine days 2-7; consolidation course + fludarabine days 4-5; during reinduction courses + fludarabine days 1-2.

Drug: Experimental (fludarabine)

The same regimen with addition of fludarabine in every treatment sequence 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. 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. Reinduction courses: Ara-C associated in the allocated group with fludarabine (20 mg/m2/d, IV) on days 1 through 2.

Other Names:

Arm B