Ignite Creation Date:
2024-05-05 @ 5:03 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00378365
Status:
UNKNOWN
Last Update Posted:
2014-04-16
First Post:
2006-09-18
Brief Title:
Acute Promyelocytic Leukemia 2006 APL
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
A Randomized Trial Assessing the Role of Arsenic Trioxide andor ATRA During Consolidation Course in Newly Diagnosed Acute Promyelocytic Leukemia APL
Status:
UNKNOWN
Status Verified Date:
2007-03
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To assess the role of Arsenic trioxide andor 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 Description:
Definition Extended description of the protocol including information not already contained in other fields such as comparisons studied
APL is a specific type of acute myeloid leukemia AML characterized by its morphology M3 or M3v in the FAB classification t1517 translocation leading to PML-RARa fusion gene and by a specific coagulopathy combining DIC 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 to those of the best arm of APL 93 trial but with less toxicity and only 2 to 3 death in CR were seen including in elderly patients
Arsenic trioxide As2O3 or ATO is an effective agent in relapsing or refractory APL which induced 85 hematological and 79 molecular CR rates in a pivotal US study The interest of ATO in the front-line therapy of newly-diagnosed APL has been strongly suggested in three studies which showed high complete remission rate low incidence of relapse and limited toxicity
In this study patients will be stratified based on age 70 years and 70 years and WBC count at diagnosis WBC10000mm3 and 10000 mm3
-Patients aged 70 years or less with WBC10000mm3
In this population about 70 of APL the best treatment group of APL2000 trial ATRA with early introduction of anthracycline-AraC chemotherapy but where Idarubicin will be substituted for Daunorubicin followed by 2 anthracycline-AraC consolidation courses and maintenance combining continuous chemotherapy and intermittent ATRA will be compared to the same regimen but without AraC during consolidation courses which will be replaced by
either ATO
or ATRA 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
Patients aged 70 years or less with WBC10000mm3 Patients ages 70 years or less with initial WBC counts 10000mm3 ie very high counts for APL which represent about 20 of APL remain at relatively high risk of relapse even with the current reference treatment The main objective of the study will be to test the addition of ATO during consolidation courses to our current standard ATRA and chemotherapy regimen Patients will receive the best treatment group of APL 2000 trial but where Idarubicin will be substituted for Daunorubicin with or without ATO during the 2 consolidation cycles
Patients older than 70 years with WBC10000 mm3 Elderly patients with initial WBC 10000m3 about 8 of APL and no contra indication to this treatment will receive a regimen with reduced cumulative dose of chemotherapy but addition of ATO during consolidation courses and during the first year of maintenance treatment The main purpose of this non randomized part of the trial is to reduce the early death mortality and death in CR observed in elderly patients without increasing the relapse rate
Patients older than 70 years with WBC10000 mm3 Elderly patients with initial WBC 10000m3 about 2 to 3 of APL and no contra indication to intensive regimen will receive the same regimen as those with low WBC but with moderate doses of Aracytine during the induction and during the first consolidation course The main purpose of this non randomized part of the trial is to reduce the early death mortality and death in CR observed in elderly patients without increasing the relapse rate
APL is a specific type of acute myeloid leukemia AML characterized by its morphology M3 or M3v in the FAB classification t1517 translocation leading to PML-RARa fusion gene and by a specific coagulopathy combining DIC 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 to those of the best arm of APL 93 trial but with less toxicity and only 2 to 3 death in CR were seen including in elderly patients
Arsenic trioxide As2O3 or ATO is an effective agent in relapsing or refractory APL which induced 85 hematological and 79 molecular CR rates in a pivotal US study The interest of ATO in the front-line therapy of newly-diagnosed APL has been strongly suggested in three studies which showed high complete remission rate low incidence of relapse and limited toxicity
In this study patients will be stratified based on age 70 years and 70 years and WBC count at diagnosis WBC10000mm3 and 10000 mm3
-Patients aged 70 years or less with WBC10000mm3
In this population about 70 of APL the best treatment group of APL2000 trial ATRA with early introduction of anthracycline-AraC chemotherapy but where Idarubicin will be substituted for Daunorubicin followed by 2 anthracycline-AraC consolidation courses and maintenance combining continuous chemotherapy and intermittent ATRA will be compared to the same regimen but without AraC during consolidation courses which will be replaced by
either ATO
or ATRA 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
Patients aged 70 years or less with WBC10000mm3 Patients ages 70 years or less with initial WBC counts 10000mm3 ie very high counts for APL which represent about 20 of APL remain at relatively high risk of relapse even with the current reference treatment The main objective of the study will be to test the addition of ATO during consolidation courses to our current standard ATRA and chemotherapy regimen Patients will receive the best treatment group of APL 2000 trial but where Idarubicin will be substituted for Daunorubicin with or without ATO during the 2 consolidation cycles
Patients older than 70 years with WBC10000 mm3 Elderly patients with initial WBC 10000m3 about 8 of APL and no contra indication to this treatment will receive a regimen with reduced cumulative dose of chemotherapy but addition of ATO during consolidation courses and during the first year of maintenance treatment The main purpose of this non randomized part of the trial is to reduce the early death mortality and death in CR observed in elderly patients without increasing the relapse rate
Patients older than 70 years with WBC10000 mm3 Elderly patients with initial WBC 10000m3 about 2 to 3 of APL and no contra indication to intensive regimen will receive the same regimen as those with low WBC but with moderate doses of Aracytine during the induction and during the first consolidation course The main purpose of this non randomized part of the trial is to reduce the early death mortality and death in CR observed in elderly patients without increasing the relapse rate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None