Clinical Trial: Acute Promyelocytic Leukemia 2006 (APL)
Study Status: Active, not recruiting
Recruit Status: Unknown status
Study Type: Interventional
Official Title: A Randomized Trial Assessing the Role of Arsenic Trioxide and/or ATRA During Consolidation Course in Newly Diagnosed Acute Promyelocytic Leukemia (APL)
Brief Summary: To assess the role of Arsenic trioxide and/or ATRA during consolidation course in APL. It is hoped that the investigational arms will further increase the event-free survival at 2 years, with reduced toxicity and without increasing the relapse rate by comparison with a classical anthracycline-AraC consolidation regimen.
Detailed Summary:
Definition: Extended description of the protocol, including information not already contained in other fields, such as comparison(s) studied.
APL is a specific type of acute myeloid leukemia (AML) characterized by its morphology (M3 or M3v in the FAB classification), t(15;17) translocation leading to PML-RARa fusion gene, and by a specific coagulopathy combining D.I.C., fibrinolysis and non specific proteolysis. ATRA can differentiate APL blasts in VITRO and in vivo. The combination of ATRA and anthracycline based chemotherapy yields CR rates greater than 90% in newly diagnosed APL. With early introduction of anthracycline AraC chemotherapy during induction treatment, and maintenance combining continuous 6MP and MTX to intermittent ATRA, the relapse risk in APL therefore now appears to be in the range of 10 to 15%.
Nevertheless, 5 to 10% of the patients do not achieve CR and 10% to 15% still relapse. Another subset of patients (5 to 7% in APL 93 trial including 17% of patients aged greater than 65 years) die in CR, from complications of the consolidation treatment phase, mainly from infection during chemotherapy induced aplasia. Failure to achieve CR with current treatment approaches is almost exclusively due to early death during induction treatment. Causes of death are predominantly bleeding, ATRA syndrome and less often infection. Early deaths predominate in elderly patients and patients with high WBC counts. Reducing the amount of chemotherapy administered to newly diagnosed APL patients diminishes this toxicity. The Spanish PETHEMA group reported results of two successive phase II trials in newly diagnosed APL with ATRA and chemotherapy with intercalating agents (idarubicin and mitoxantrone) without AraC followed by maintenance combining ATRA and low dose chemotherapy (LPA96 and LPA99 trials). Results appeared similar
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome:
- For Patients aged 70 years or less with WBC<10.000/mm3, The primary end point will be event free survival at 2 years from CR achievement [ Time Frame: during de study ]For Patients aged 70 years or less with WBC<10.000/mm3, The primary end point
- For patients older than 70 years with WBC>10.000 /mm3, The primary end point will be EFS at 2 years from diagnosis [ Time Frame: during the study ]For patients older than 70 years with WBC>10.000 /mm3, The primary end point will be EFS at 2 years from diagnosis
Original Primary Outcome:
- For Patients aged 70 years or less with WBC<10.000/mm3, The primary end point will be event free survival at 2 years from CR achievement
- For Patients aged 70 years or less with WBC>10.000/mm3, The primary end point will be the Relapse (molecular or hematological).
- For Patients older than 70 years with WBC<10.000 /mm3, The primary end point will be EFS at 2 years from diagnosis.
- For patients older than 70 years with WBC>10.000 /mm3, The primary end point will be EFS at 2 years from diagnosis
Current Secondary Outcome:
- For Patients aged 70 years or less with WBC<10.000/mm3 : [ Time Frame: during the study ]For Patients aged 70 years or less with WBC<10.000/mm3 :
- Relapse (molecular or hematological). [ Time Frame: during the study ]Relapse (molecular or hematological).
- Kinetics of decrease of PML-RARA transcript level during and after consolidation course. [ Time Frame: during the study ]Kinetics of decrease of PML-RARA transcript level during and after consolidation course.
- Survival at 2 years. [ Time Frame: during the study ]Survival at 2 years.
- Side effects of the treatment, including treatment-related mortality and morbidity of consolidation treatment. [ Time Frame: during th study ]Side effects of the treatment, including treatment-related mortality and morbidity of consolidation treatment.
- Days on antibiotics, transfusion requirement and nights spent in Hospital [ Time Frame: during the study ]Days on antibiotics, transfusion requirement and nights spent in Hospital
- For Patients aged 70 years or less with WBC>10.000/mm3 [ Time Frame: during the study ]For Patients aged 70 years or less with WBC>10.000/mm3
- event free survival at 2 years from CR achievement [ Time Frame: during the study ]event free survival at 2 years from CR achievement
- Side effects of the treatment, including treatment-related mortality and morbidity of consolidation treatment. [ Time Frame: during the study ]Side effects of the treatment, including treatment-related mortality and morbidity of consolidation treatment.
- For Patients older than 70 years with WBC<10.000 /mm3 [ Time Frame: during the study ]For Patients older than 70 years with WBC<10.000 /mm3
- Kinetics of decrease of PML-RARA transcript level during and after consolidation course. [ Time Frame: during the study ]Kinetics of decrease of PML-RARA transcript level during and after
- Relapse and survival at 2 years. [ Time Frame: during the study ]Relapse and survival at 2 years.
- Side effects of the treatment, including mortality and morbidity of consolidation treatment. [ Time Frame: during the study ]Side effects of the treatment, including mortality and morbidity of
- For patients older than 70 years with WBC>10.000 /mm3 [ Time Frame: during the study ]For patients older than 70 years with WBC>10.000 /mm3
Original Secondary Outcome:
- For Patients aged 70 years or less with WBC<10.000/mm3 :
- Relapse (molecular or hematological).
- Kinetics of decrease of PML-RARA transcript level during and after consolidation course.
- Survival at 2 years.
- Side effects of the treatment, including treatment-related mortality and morbidity of consolidation treatment.
- Days on antibiotics, transfusion requirement and nights spent in Hospital
- For Patients aged 70 years or less with WBC>10.000/mm3
- event free survival at 2 years from CR achievement
- For Patients older than 70 years with WBC<10.000 /mm3
- Relapse and survival at 2 years.
- Side effects of the treatment, including mortality and morbidity of consolidation treatment.
- For patients older than 70 years with WBC>10.000 /mm3
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: September 18, 2006
Date Started: October 2006
Date Completion: September 2016
Last Updated: April 15, 2014
Last Verified: March 2007
