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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00925873
• Other study ID #: GOELAMS SA4
• Status: Completed
• Phase: Phase 3
• First received: March 31, 2009
• Last updated: June 19, 2009
• Start date: June 1996
• Est. completion date: November 2004

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: November 2004
• Est. primary completion date: April 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

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)
• 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.

Locations

Country	Name	City	State
France	GOELAMS	Tours

Sponsors (3)

Lead Sponsor	Collaborator
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS	Novartis, Schering SA

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival (EFS)		long term results (median follow up: 71 months)	Yes
Secondary	evaluation of the CR rate, remission duration disease-free survival (DFS) overall survival (OS),		long term results (median follow up: 71 months)	Yes