NCT00599937

Brief Summary

Objectives of the trial were to assess the optimal timing of chemotherapy with or after ATRA and the role of maintenance therapy.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
576

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jan 1993

Longer than P75 for phase_3

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 1993

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 1998

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 1998

Completed
9.1 years until next milestone

First Submitted

Initial submission to the registry

December 27, 2007

Completed
28 days until next milestone

First Posted

Study publicly available on registry

January 24, 2008

Completed
Last Updated

January 24, 2008

Status Verified

December 1, 2007

Enrollment Period

5.9 years

First QC Date

December 27, 2007

Last Update Submit

January 23, 2008

Conditions

Keywords

APL

Outcome Measures

Primary Outcomes (1)

  • For induction treatment event-free survival (EFS), calculated from the date of randomization, was the major endpoint.

    2 years

Study Arms (7)

ATRA ->Chemo

NO INTERVENTION

Patients 65 years of age with a WBC count less than 5,000 were randomized to receive the reference ATRA treatment of our previous trial (APL91 trial), ie, 45 mg/m2/d ATRA followed by CT or ATRA plus CT (ATRA+CT). In the ATRA followed byCT group, patients received 45 mg/m2/d ATRA orally until CR, with a maximum of 90 days. After CR achievement, they received a course of 60 mg/m2/d daunorubicin (DNR) for 3 days and 200 mg/m2/d AraC for 7 days (course I). However, course I was added to ATRA if the WBC count was increased to greater than 6,000, 10,000, or 15,000 by day 5, 10, and 15 of ATRA treatment, respectively, because, from our experience, patients were at risk of ATRA syndrome above those thresholds.

ATRA+CT

EXPERIMENTAL

Patients randomized to the ATRA+CT group received the same combination of ATRA and CT, with course I of CT starting on day 3 of ATRA treatment. This 48-hour interval before onset of CT was based on our previous report, because it allowed correction of coagulopathy.

Drug: ATRA

High WBC

NO INTERVENTION

Patients with a WBC count greater than 5,000 at presentation (irrespective of their age) and patients 66 to 75 years of age with a WBC count 5,000 were not randomized but received ATRA plus CT course I from day 1 (high WBC group) and the same schedule as in the ATRA-\>CT group (elderly group), respectively.

no maintenance

NO INTERVENTION

No maintenance

maintenance ATRA

EXPERIMENTAL

Intermitent ATRA as maintenance

Drug: ATRA and or Chemo as maintenance

maintenance Cxt

EXPERIMENTAL

continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, orally) as maintenance

Drug: ATRA and or Chemo as maintenance

maintenance both

EXPERIMENTAL

continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, orally) AND ATRA as maintenance

Drug: ATRA and or Chemo as maintenance

Interventions

ATRADRUG

early introduction of ATRA

ATRA+CT

patients were randomized both to receive or not receive intermittent ATRA (45 mg/m2/d, 15 days every 3 months) and to receive or not receive continuous CT with 6 mercaptopurine (90 mg/m2/d, orally) and methotrexate (15 mg/m2/wk, orally), according to a 2-by-2 factorial design stratified on the initial induction treatment group

Also known as: ATRA
maintenance ATRAmaintenance Cxtmaintenance both

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of APL, based on morphology criteria
  • Age 75 years or less; and
  • Written informed consent. Diagnosis had to be subsequently confirmed by presence of t(15;17) or PML-RAR gene rearrangement. In the absence of t(15;17) and if no analysis of the rearrangement could be made, review of initial marrow slides by an independent morphologist was mandatory.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (2)

  • Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999 Aug 15;94(4):1192-200.

  • Ades L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, Recher C, Thomas X, Rayon C, Castaigne S, Tournilhac O, de Botton S, Ifrah N, Cahn JY, Solary E, Gardin C, Fegeux N, Bordessoule D, Ferrant A, Meyer-Monard S, Vey N, Dombret H, Degos L, Chevret S, Fenaux P; European APL Group. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood. 2010 Mar 4;115(9):1690-6. doi: 10.1182/blood-2009-07-233387. Epub 2009 Dec 17.

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

TretinoinMaintenance

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, AcuteLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vitamin ARetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesDiterpenesPigments, BiologicalBiological FactorsHealth Care Facilities Workforce and Services

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 24, 2008

Study Start

January 1, 1993

Primary Completion

December 1, 1998

Study Completion

December 1, 1998

Last Updated

January 24, 2008

Record last verified: 2007-12