APL93: Timing of CxT and Role of Maintenance

Leukemia, Promyelocytic, Acute Clinical Trial

Official title:

Assessment of the Optimal Timing of Chemotherapy With or After ATRA and the Role of Maintenance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00599937
• Other study ID #: APL93
• Status: Completed
• Phase: Phase 3
• First received: December 27, 2007
• Last updated: January 23, 2008
• Start date: January 1993
• Est. completion date: December 1998

Study information

• Verified date: December 2007
• Source: Groupe d'etude et de travail sur les leucemies aigues promyelocytaires
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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

Description:

Induction treatment was stratified by age and initial WBC count. Patients ≤65 years of age with a WBC count less than 5,000/µL were randomized to receive the reference ATRA treatment of our previous trial (APL91 trial) {Fenaux, 1993 #2088}, ie, 45 mg/m2/d ATRA followed by CT (ATRA→CT group) or ATRA plus CT (ATRA+CT). In the ATRA→CT 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/µL, 10,000/µL, or 15,000/µL by day 5, 10, and 15 of ATRA treatment, respectively, be-cause, from our experience, patients were at risk of ATRA syndrome above those thresholds{de Botton, 2003 #1127; De Botton, 1998 #1604}. 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.

Patients with a WBC count greater than 5,000/µL at presentation (irrespective of their age) and patients 66 to 75 years of age with a WBC count ≤ 5,000/µL were not ran-domized 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.

Treatment of coagulopathy during the induction phase was based on platelet support to maintain the platelet count at a level greater than 50,000 /µL until the disappea-rance of coagulopathy. The use of heparin, tranexamic acid, fresh frozen plasma, and fibrinogen transfusions was optional.

CR patients received 2 CT consolidation courses, including course II (identical to course I) and course III, consisting of 45 mg/m2/d DNR for 3 days and 1 g/m2 AraC every 12 hours for 4 days. The elderly group only received course II.

Three to 4 weeks after hematological recovery from this consolidation CT, patients who were still in CR 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, oral-ly), according to a 2-by-2 factorial design stratified on the initial induction treatment group. Maintenance treatment was scheduled for 2 years. Randomizations for induc-tion and maintenance, stratified on center, were performed through a centralized tele-phone assignment procedure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 576
• Est. completion date: December 1998
• Est. primary completion date: December 1998
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Diagnosis of APL, based on morphology criteria

2. Age 75 years or less; and

3. 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Promyelocytic, Acute

Intervention

Drug:
• ATRA
early introduction of ATRA
• ATRA and or Chemo as maintenance
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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Groupe d'etude et de travail sur les leucemies aigues promyelocytaires	DRC lille, France

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For induction treatment event-free survival (EFS), calculated from the date of randomization, was the major endpoint.		2 years	No