Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
Schering SA
Novartis
Information provided by:
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
ClinicalTrials.gov Identifier:
NCT00925873
First received: March 31, 2009
Last updated: June 19, 2009
Last verified: June 2009
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Drug: Active comparator (no fludarabine)
Drug: Experimental (fludarabine)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: long term results (median follow up: 71 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • evaluation of the CR rate, remission duration disease-free survival (DFS) overall survival (OS), [ Time Frame: long term results (median follow up: 71 months) ] [ Designated as safety issue: Yes ]

Enrollment: 303
Study Start Date: June 1996
Study Completion Date: November 2004
Primary Completion Date: April 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: 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)
Other Name: Arm A
Experimental: 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.
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.
Other Name: Arm B

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.

  Eligibility

Ages Eligible for Study:   60 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00925873

Locations
France
GOELAMS
Tours, France, 37000
Sponsors and Collaborators
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Schering SA
Novartis
Investigators
Principal Investigator: Francis WITZ, MD Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
  More Information

Additional Information:
No publications provided

Responsible Party: Dr Francis WITZ, GOELAMS
ClinicalTrials.gov Identifier: NCT00925873     History of Changes
Other Study ID Numbers: GOELAMS SA4
Study First Received: March 31, 2009
Last Updated: June 19, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:
Fludarabine
AML
elderly patients

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Fludarabine
Fludarabine phosphate
Vidarabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014