Viewing Study NCT00428558



Ignite Creation Date: 2024-05-05 @ 5:16 PM
Last Modification Date: 2024-10-26 @ 9:30 AM
Study NCT ID: NCT00428558
Status: COMPLETED
Last Update Posted: 2013-12-20
First Post: 2007-01-29

Brief Title: Timed-Sequential Induction in CBF-AML
Sponsor: Assistance Publique - Hôpitaux de Paris
Organization: Assistance Publique - Hôpitaux de Paris

Study Overview

Official Title: A Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor CBF Acute Myeloid Leukemia AML
Status: COMPLETED
Status Verified Date: 2007-07
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: Core binding factor CBF acute myeloid leukemias AML include AMLs carrying the t821 translocation as well as AMLs carrying either the inversion of chromosome 16 or translocation t1616 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
Detailed Description: Core binding factor CBF acute myeloid leukemias AML include AMLs carrying the t821 translocation as well as AMLs carrying either the inversion of chromosome 16 or translocation t1616 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 Initial high white blood cell count activating mutations of cKit Ras and FLT3 genes and persistence of high minimal residual disease MRD levels as evidenced by AML1-ETO or CBFb-MYH11 specific RQ-PCR tools are the main bad-prognostic factors in patients with CBF-AML

This project includes a new single French protocol to treat patients with CBF-AML who represent approximately 15 of all AML patients This common protocol has been elaborated by the two main French cooperative groups for adult AML ALFA and GOELAMS In addition to a unique specific therapeutical strategy this protocol includes the biological characterization of the heterogeneity of these diseases gene mutation and transcription profiles as well as a centralized MRD monitoring and centralized evaluation of pharmacogenetic polymorphisms This project which is well-positioned in the international competition will use many platforms of the POLECANCER with the following objectives 1 to improve the results of the treatment of CBF-AML patients 2 to organize a French clinical and biological network on CBF-AML with the aim to test new targeted therapeutical agents tyrosine kinase andor farnesyl transferase inhibitors in the next future

TREATMENT DESIGN Induction course Systematic timed-sequential induction arm A DAUNORUBICINE DNR 60 mgm2day IV 30 min Day 1 2 and 3 CYTARABINE AraC 500 mgm2day Continuous infusion Day 1 to 3 DAUNORUBICINE DNR 35 mgm2day IV 30 min Day 8 and 9 CYTARABINE AraC 1 grm212 h IV 2h Day 8 9 and 10 Response-adapted timed-sequential induction arm G DAUNORUBICINE DNR 60 mgm2dayIV 30 min Day 1 2 and 3 CYTARABINE AraC 200 mgm2dayContinuous infusion Day 1 to 7

Peripheral blood and bone marrow evaluation at Day 15 The following second induction course will be administered in patients with persistent marrow disease at Day 15

DAUNORUBICINE DNR 35 mgm2day IV 30 min Day 16 and 17 CYTARABINE AraC1 grm212 h IV 2h Day 16 17 and 18 Persistent marrow disease at Day 15 is defined by more than 10 leukemic blasts in a non aplastic or non very hypoplastic bone marrow aspiration sample

Salvage course In patients not reaching CR after the first induction course either SI or TSI a salvage course will be administered Salvage therapy should not be initiated before Day 35 of arm A and Day 42 of arm G

CYTARABINE AraC 3 grm212h IV 2h Day 1 3 5 and 7 AMSACRINE 100 mgm2day IV 30 min Day 5 to 7 G-CSF lenograstim from Day 8 until myeloid recovery 500 PMNµL

Consolidation cycles Three monthly cycles of consolidation will be administered in all patients reaching hematological CR after induction or induction salvage

CYTARABINE AraC 3 gm212h IV 2h Day 1 3 and 5 G-CSF lenograstim from Day 8 until myeloid recovery 500 PMNµL

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None