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

NCT ID: NCT00925873

Last Updated: 2009-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 303 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-06-30
• Study Completion Date: 2004-11-30

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Control arm without fludarabine

1. 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;

2. Consolidation course: Ara-C 1g/m2 q12h days 1-3, idarubicin 10mg/m2 days 2-3;

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.

Group Type: ACTIVE_COMPARATOR

Active comparator (no fludarabine)

Intervention Type: DRUG

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)

2

Fludarabine arm

The same regimen with fludarabine 20 mg/m2/day IV for 30 minutes

1. induction course + fludarabine days 2-7;

2. consolidation course + fludarabine days 4-5;

3. during reinduction courses + fludarabine days 1-2.

Group Type: EXPERIMENTAL

Experimental (fludarabine)

Intervention Type: DRUG

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.

Interventions

Active 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)

Intervention Type: DRUG

Experimental (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.

Intervention Type: DRUG

Other Intervention Names

Arm A; Arm B

Eligibility Criteria

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schering SA

UNKNOWN

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

French Innovative Leukemia Organisation

OTHER

Sponsor Role: lead

Responsible Party

GOELAMS

Principal Investigators

Francis WITZ, MD

Role: PRINCIPAL_INVESTIGATOR

French Innovative Leukemia Organisation

Locations

GOELAMS

Tours, , France

Countries

France

Other Identifiers

GOELAMS SA4

Identifier Type: -

Identifier Source: org_study_id