NCT00428558

Brief Summary

Core binding factor (CBF) acute myeloid leukemias (AML) include AMLs carrying the t(8;21) translocation as well as AMLs carrying either the inversion of chromosome 16 or translocation t(16;16). CBF-AMLs are characterized by their high sensitivity to standard chemotherapeutical agents, especially to cytarabine when administered as high-dose bolus infusions, and thus by a relative good prognosis. However, relapse rates are still comprised between 30 and 50% in these patients, even if overall survival may reach approximately 65% due to the potential salvage of late relapses. The primary purpose of the protocol is to compare two modalities of timed-sequential induction in order to improve the results of the treatment of CBF-AML patients. This protocol also includes the biological characterization of the heterogeneity of these diseases (gene mutation and transcription profiles), as well as a centralized minimal residual disease monitoring and centralized evaluation of pharmacogenetic polymorphisms.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jul 2007

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 29, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 30, 2007

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2007

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2011

Completed
Last Updated

December 20, 2013

Status Verified

July 1, 2007

Enrollment Period

3.9 years

First QC Date

January 29, 2007

Last Update Submit

December 19, 2013

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemiaCore Binding Factort(8;21)inv(16)timed-sequential induction

Outcome Measures

Primary Outcomes (1)

  • The primary objective of the study is to increase the Event-free Survival (EFS)

    during the 60 months

Secondary Outcomes (8)

  • The complete remission (CR) rate, molecular response (MRD), cumulative incidence of relapse (CIR), disease-free survival (DFS), and overall survival (OS) in both randomization groups.

    during the 60 months

  • The toxicity of both induction strategies (induction deaths and further deaths in first CR).

    during the 60 months

  • The relative prognostic value of : 1) WBC; 2) Mutational status (FLT3, c-Kit, and Ras mutations); and 3) MRD in patient outcome (CR rate, CIR, EFS, DFS, OS).

    during the 60 months

  • The prognostic value of CBF-AML subsets defined on Gene Expression Profiling (GEP) basis.

    during the 60 months

  • The prognostic impact of known polymorphisms of genes involved in the metabolism of cytarabine and anthracyclines (Pharmacogenetic study).

    during the 60 months

  • +3 more secondary outcomes

Study Arms (2)

2

ACTIVE COMPARATOR

A Phase 3 Trial of Systematic versus Response-adapted Timed-SEQUENTIAL Induction in Patients with Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

Drug: Chemotherapy (DAUNORUBICINE-CYTARABINE)

1

EXPERIMENTAL

BRAS INDUCTION SEQUENTIAL

Drug: Chemotherapy (DAUNORUBICINE-CYTARABINE)

Interventions

Chemotherapy (DAUNORUBICINE-CYTARABINE)DRUG

A Phase 3 Trial of Systematic versus Response-adapted Timed-SEQUENTIAL Induction in Patients with Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

2

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Patients aged 18-60 years.
  • With a newly-diagnosed de novo or therapy-related CBF-AML defined

You may not qualify if:

  • No previously treated with any anti-leukemic agent.
  • No presenting any diagnosis of uncontrolled or metastatic tumor.
  • OMS performance status \< 2,
  • Absence of uncontrolled severe infection,
  • AST and ALT 2.5 x ULN,
  • Total bilirubin 1.5 x ULN,
  • Serum creatinine 1.5 x ULN

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Service Hematologie Oncologie

Nîmes, 30029, France

Location

Related Publications (4)

  • Appelbaum FR, Kopecky KJ, Tallman MS, Slovak ML, Gundacker HM, Kim HT, Dewald GW, Kantarjian HM, Pierce SR, Estey EH. The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol. 2006 Oct;135(2):165-73. doi: 10.1111/j.1365-2141.2006.06276.x. Epub 2006 Aug 25.

    PMID: 16939487RESULT

  • Willekens C, Blanchet O, Renneville A, Cornillet-Lefebvre P, Pautas C, Guieze R, Ifrah N, Dombret H, Jourdan E, Preudhomme C, Boissel N; French AML Intergroup. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial. Haematologica. 2016 Mar;101(3):328-35. doi: 10.3324/haematol.2015.131946. Epub 2015 Dec 3.

    PMID: 26635039DERIVED

  • Duployez N, Nibourel O, Marceau-Renaut A, Willekens C, Helevaut N, Caillault A, Villenet C, Celli-Lebras K, Boissel N, Jourdan E, Dombret H, Figeac M, Preudhomme C, Renneville A. Minimal residual disease monitoring in t(8;21) acute myeloid leukemia based on RUNX1-RUNX1T1 fusion quantification on genomic DNA. Am J Hematol. 2014 Jun;89(6):610-5. doi: 10.1002/ajh.23696. Epub 2014 Mar 8.

    PMID: 24616160DERIVED

  • Jourdan E, Boissel N, Chevret S, Delabesse E, Renneville A, Cornillet P, Blanchet O, Cayuela JM, Recher C, Raffoux E, Delaunay J, Pigneux A, Bulabois CE, Berthon C, Pautas C, Vey N, Lioure B, Thomas X, Luquet I, Terre C, Guardiola P, Bene MC, Preudhomme C, Ifrah N, Dombret H; French AML Intergroup. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood. 2013 Mar 21;121(12):2213-23. doi: 10.1182/blood-2012-10-462879. Epub 2013 Jan 15.

    PMID: 23321257DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

  • Eric JOURDAN, MD,PhD

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 29, 2007

First Posted

January 30, 2007

Study Start

July 1, 2007

Primary Completion

June 1, 2011

Study Completion

June 1, 2011

Last Updated

December 20, 2013

Record last verified: 2007-07

Locations

FR(1)