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

NCT00591526 | Completed Phase 3 DMC

• 1 other identifier: APL2000
• Study Type: interventional
• Target: 250
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Leukemia, Promyelocytic, Acute

Keywords

APL

Outcome Measures

Primary Outcomes (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 Outcomes (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

Study Arms (4)

A

NO INTERVENTION

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 1. 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) 2. 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 1. Continuous low dose chemotherapy 2. Intermittent ATRA

B

EXPERIMENTAL

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

Drug: Arac

C

NO INTERVENTION

1. 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) 2. 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

D

NO INTERVENTION

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 1. First consolidation course DNR 60 mg/m2/d d1-3 AraC 100 mg/m2/d d1-5 G-CSF 2. 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

Interventions

Arac DRUG

Ommit ARAC in the chemotherapy

Also known as: Cytarabine

B; D

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

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

Related Publications (1)

• 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.

  PMID: 17116939 RESULT

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Pierre Fenaux, MD

  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

Study Record Dates

• First Submitted: December 27, 2007
• First Posted: January 11, 2008
• Study Start: June 1, 2000
• Primary Completion: June 1, 2004
• Study Completion: June 1, 2004
• Last Updated: January 14, 2008

Record last verified: 2008-01