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A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)

Primary Purpose

Leukemia, Promyelocytic, Acute

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Arac
Sponsored by
Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Promyelocytic, Acute focused on measuring APL

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • diagnosis of APL based on morphological grounds, and which will have to be confirmed by presence of t(15;17) and/or PML-RARα rearrangement (if RT-PCR for APL cannot be performed at your center, send fresh cells to Prof.C.Chomienne, Centre Hayem, Hopital St.Louis, 1 av. Claude Vellefaux, 75475 PARIS or keep frozen RNA [not frozen cells, as the RNA yield for PML-RAR is often poor in those cells]).
  • untreated patient
  • no contraindication to intensive chemotherapy (especially cardiac contraindication to daunorubicin)
  • in female patients : absence of pregnancy and adequate contraceptive method (due to teratogenetic effects of ATRA in early pregnancy)
  • written informed consent.

Exclusion Criteria:

  • patients already treated
  • patients with contraindication to intensive chemotherapy, especially cardiac contraindication to daunorubicin
  • in female patients : pregnancy or absence of adequate contraceptive methods

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    No Intervention

    Experimental

    No Intervention

    No Intervention

    Arm Label

    A

    B

    C

    D

    Arm Description

    Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 Induction treatment a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days AraC 200 mg/m2/d during 7 days 2) Consolidation treatment First consolidation course (=2nd chemotherapy course) DNR 60 mg/m2/d d1-3 (intravenous bolus injection) AraC 200 mg/m2/d d1-7 (continuous infusion) Second consolidation course AraC 1g/m2/12h d1-4 (1 hour infusion) Daunorubicin 45 mg/m2/d d1-3 (intravenous bolus injection) 3) Maintenance treatment Consists of the combination of continuous low dose chemotherapy and intermittent ATRA, during 2 years Continuous low dose chemotherapy Intermittent ATRA

    Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 (Group B) Same treatment as Group A but without AraC.

    First consolidation course (=2nd chemotherapy course) DNR 60 mg/m2/d d1-3 (intravenous bolus injection) AraC 200 mg/m2/d d1-7 (continuous infusion) Second consolidation course AraC 1g/m2/12h d1-4 (1 hour infusion) Daunorubicin 45 mg/m2/d d1-3 (intravenous bolus injection) CNS prophylaxis : consists of 5 intrathecal (IT) injections of MTX 15mg and AraC 50 mg (12 mg/m2 maximum 15 mg, and 30mg/m2, maximum 50 mg, respectively, in children) + depomedrol IT. I 3) Maintenance treatment

    Patients aged >60 years and initial WBC ≤ 10000/mm3 Induction treatment a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days (intravenous bolus injection) NO ARA C DURING THIS FIRST COURSE 2) Consolidation treatment First consolidation course DNR 60 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF Second consolidation course DNR45 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF 3) maintenance treatment: similar to other groups

    Outcomes

    Primary Outcome Measures

    for patients with initial WBC counts > 10000/mm3 - the main end point for this second randomization is relapse at 2 years

    Secondary Outcome Measures

    secondary end points are : complete remission rate ; survival and event free survival at 2 years, and quality-adjusted survival (Q-TWiST). secondary end points are : survival and event free survival at 2 years

    Full Information

    First Posted
    December 27, 2007
    Last Updated
    January 11, 2008
    Sponsor
    Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
    Collaborators
    University Hospital, Lille
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00591526
    Brief Title
    A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)
    Official Title
    A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed Acute Promyelocytic Leukemia (APL)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2008
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2000 (undefined)
    Primary Completion Date
    June 2004 (Actual)
    Study Completion Date
    June 2004 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
    Collaborators
    University Hospital, Lille

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The first purpose of this randomized trial will be to compare the best treatment group of APL 93 trial (ATRA with early introduction of anthracycline-AraC chemotherapy, followed by 2 consolidation anthracycline-AraC courses and maintenance combining continuous chemotherapy and intermittent ATRA) to the same regimen, but without AraC. It is hoped that the investigational arm, with anthracycline alone chemotherapy (without AraC), will have reduced toxicity without increasing the incidence of relapse, by comparison with a classical induction/consolidation anthracycline-AraC regimen Thus : the main end point for this first randomization is relapse at 2 years secondary end points are : complete remission rate ; survival and event free survival at 2 years, and quality-adjusted survival (Q-TWiST). 2) Because patients with initial WBC counts > 10000/mm3 (ie very high counts for APL) appear to remain at relatively high risk of relapse even with the current reference treatment, they will not be included in this trial that assesses the reduction of chemotherapy. On the contrary: i) they will all receive the standard chemotherapy (best treatment group of APL 93 trial); Thus : the main end point for this second randomization is relapse at 2 years secondary end points are : survival and event free survival at 2 years 3)Elderly patients with initial WBC ≤ 10000/m3 will receive consolidation chemotherapy without AraC during the first chemotherapy course, and reduced doses of AraC during the second and third course, followed by G-CSF.
    Detailed Description
    All patients will receive induction treatment with ATRA and a first chemotherapy course, followed by two consolidation chemotherapy courses and maintenance with continuous low dose chemotherapy and intermittent ATRA. Initial stratification will be based on age and WBC count. Patients aged 60 years with initial WBC 10 00 will all receive the reference AraC+ group (Group A ) (no randomization). Patients with initial WBC > 10000/mm3 will initially all be treated according to the AraC+ group. Patients > 60 years and with initial WBC ≤ 10000/mm3) will be only registered, without randomization (Group D) and will receive the reference AraC+ group ,but without AraC during the first chemotherapy course ,and with reduced doses of AraC during the second and third course, followed by G-CSF. .

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Leukemia, Promyelocytic, Acute
    Keywords
    APL

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    250 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    A
    Arm Type
    No Intervention
    Arm Description
    Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 Induction treatment a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days AraC 200 mg/m2/d during 7 days 2) Consolidation treatment First consolidation course (=2nd chemotherapy course) DNR 60 mg/m2/d d1-3 (intravenous bolus injection) AraC 200 mg/m2/d d1-7 (continuous infusion) Second consolidation course AraC 1g/m2/12h d1-4 (1 hour infusion) Daunorubicin 45 mg/m2/d d1-3 (intravenous bolus injection) 3) Maintenance treatment Consists of the combination of continuous low dose chemotherapy and intermittent ATRA, during 2 years Continuous low dose chemotherapy Intermittent ATRA
    Arm Title
    B
    Arm Type
    Experimental
    Arm Description
    Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 (Group B) Same treatment as Group A but without AraC.
    Arm Title
    C
    Arm Type
    No Intervention
    Arm Description
    First consolidation course (=2nd chemotherapy course) DNR 60 mg/m2/d d1-3 (intravenous bolus injection) AraC 200 mg/m2/d d1-7 (continuous infusion) Second consolidation course AraC 1g/m2/12h d1-4 (1 hour infusion) Daunorubicin 45 mg/m2/d d1-3 (intravenous bolus injection) CNS prophylaxis : consists of 5 intrathecal (IT) injections of MTX 15mg and AraC 50 mg (12 mg/m2 maximum 15 mg, and 30mg/m2, maximum 50 mg, respectively, in children) + depomedrol IT. I 3) Maintenance treatment
    Arm Title
    D
    Arm Type
    No Intervention
    Arm Description
    Patients aged >60 years and initial WBC ≤ 10000/mm3 Induction treatment a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days (intravenous bolus injection) NO ARA C DURING THIS FIRST COURSE 2) Consolidation treatment First consolidation course DNR 60 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF Second consolidation course DNR45 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF 3) maintenance treatment: similar to other groups
    Intervention Type
    Drug
    Intervention Name(s)
    Arac
    Other Intervention Name(s)
    Cytarabine
    Intervention Description
    Ommit ARAC in the chemotherapy
    Primary Outcome Measure Information:
    Title
    for patients with initial WBC counts > 10000/mm3 - the main end point for this second randomization is relapse at 2 years
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    secondary end points are : complete remission rate ; survival and event free survival at 2 years, and quality-adjusted survival (Q-TWiST). secondary end points are : survival and event free survival at 2 years
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: diagnosis of APL based on morphological grounds, and which will have to be confirmed by presence of t(15;17) and/or PML-RARα rearrangement (if RT-PCR for APL cannot be performed at your center, send fresh cells to Prof.C.Chomienne, Centre Hayem, Hopital St.Louis, 1 av. Claude Vellefaux, 75475 PARIS or keep frozen RNA [not frozen cells, as the RNA yield for PML-RAR is often poor in those cells]). untreated patient no contraindication to intensive chemotherapy (especially cardiac contraindication to daunorubicin) in female patients : absence of pregnancy and adequate contraceptive method (due to teratogenetic effects of ATRA in early pregnancy) written informed consent. Exclusion Criteria: patients already treated patients with contraindication to intensive chemotherapy, especially cardiac contraindication to daunorubicin in female patients : pregnancy or absence of adequate contraceptive methods
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pierre Fenaux, MD
    Organizational Affiliation
    Assistance Publique - Hôpitaux de Paris
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    17116939
    Citation
    Ades L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. doi: 10.1200/JCO.2006.08.1596. Epub 2006 Nov 20.
    Results Reference
    result

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    A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)

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