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

Sponsor
Groupe d'etude et de travail sur les leucemies aigues promyelocytaires (Other)
Overall Status
Completed
CT.gov ID
NCT00591526
Collaborator
University Hospital, Lille (Other)
250
4
48

Study Details

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).

  1. 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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. .

Study Design

Study Type:
Interventional
Actual Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed Acute Promyelocytic Leukemia (APL)
Study Start Date :
Jun 1, 2000
Actual Primary Completion Date :
Jun 1, 2004
Actual Study Completion Date :
Jun 1, 2004

Arms and Interventions

Arm Intervention/Treatment
No Intervention: A

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

Experimental: B

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

Drug: Arac
Ommit ARAC in the chemotherapy
Other Names:
  • Cytarabine
  • No Intervention: C

    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

    No Intervention: D

    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

    Drug: Arac
    Ommit ARAC in the chemotherapy
    Other Names:
  • Cytarabine
  • Outcome Measures

    Primary Outcome Measures

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

    Secondary Outcome Measures

    1. 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 [2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
    • University Hospital, Lille

    Investigators

    • Principal Investigator: Pierre Fenaux, MD, Assistance Publique - Hôpitaux de Paris

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00591526
    Other Study ID Numbers:
    • APL2000
    First Posted:
    Jan 11, 2008
    Last Update Posted:
    Jan 14, 2008
    Last Verified:
    Jan 1, 2008
    Keywords provided by , ,
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 14, 2008