Clinical trial NCT00591526: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia, Promyelocytic, Acute
Keywords: APL
Lead sponsor: Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
Sponsor class: OTHER
Collaborators: name: University Hospital, Lille
First posted: 2008-01-11
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. .

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

Primary outcomes:
measure: for patients with initial WBC counts > 10000/mm3 - the main end point for this second randomization is relapse at 2 years
timeFrame: 2 years
Secondary outcomes:
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Pierre Fenaux, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.