Ignite Creation Date:
2025-12-25 @ 2:46 AM
Ignite Modification Date:
2025-12-26 @ 1:26 AM
Study NCT ID:
NCT00465933
Status:
COMPLETED
Last Update Posted:
2008-03-31
First Post:
2007-04-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Treatment of Acute Promyelocytic Leukemia With All-Trans Retinoic Acid (ATRA) and Idarubicin (AIDA)
Sponsor:
PETHEMA Foundation
Organization:
Study Overview
Official Title:
Treatment of Acute Promyelocytic Leukemia: Remission Induction With ATRA + Idarubicin (AIDA) Risk Adapted Intensity of Consolidation and Addition of ATRA Maintenance With ATRA + Methotrexate + Mercaptopurine Salvage Therapy for Molecular and Haematological Relapses
Status:
COMPLETED
Status Verified Date:
2008-03
Last Known Status:
None
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:
The purpose of this study is to evaluate the efficacy of all-trans retinoic acid (ATRA) and idarubicin (AIDA) with a dose reduction in patients older than 70 years of age in the remission induction of acute promyelocytic leukemia (APL).
With regard to the induction, the excellent results obtained by the combination of ATRA and idarubicin (AIDA), especially in terms of antileukemic efficacy (1% of resistance), do not support the introduction of substantial changes in this combination. However, given that most of the induction failures were caused by complications, especially of a hemorrhagic nature, and that these had a major impact in the hyperleukocytic forms and in patients older than 70 years of age, the induction was modified as follows:
1. Reduction of idarubicin dose in patients older than 70 years of age (three days instead of four);
2. Early administration of corticosteroid therapy in all patients as ATRA syndrome prophylaxis. A preliminary analysis of the Italian Group for Adult Hematologic Diseases (Gruppo Italiano Malattie Ematologiche dell'Adulto, GIMEMA) has shown that low dose prednisone use in a prophylactic manner appears to reduce the incidence and severity of the ATRA syndrome, which could also have a favorable impact on the hemorrhagic mortality (non-published data); and
3. Treatment of the hyperfibrinolysis with an antifibrinolytic agent (tranexamic acid). It has been recently reported that APL cells present abnormally high levels of annexins (especially annexin II), and that these levels may provide the fundamental mechanism for the hemorrhagic complications in APL by increasing the production of t-PA dependent plasmin. These findings provide new reasons for the introduction of tranexamic acid in the hemorrhagic prophylaxis of APL.
With regard to the induction, the excellent results obtained by the combination of ATRA and idarubicin (AIDA), especially in terms of antileukemic efficacy (1% of resistance), do not support the introduction of substantial changes in this combination. However, given that most of the induction failures were caused by complications, especially of a hemorrhagic nature, and that these had a major impact in the hyperleukocytic forms and in patients older than 70 years of age, the induction was modified as follows:
1. Reduction of idarubicin dose in patients older than 70 years of age (three days instead of four);
2. Early administration of corticosteroid therapy in all patients as ATRA syndrome prophylaxis. A preliminary analysis of the Italian Group for Adult Hematologic Diseases (Gruppo Italiano Malattie Ematologiche dell'Adulto, GIMEMA) has shown that low dose prednisone use in a prophylactic manner appears to reduce the incidence and severity of the ATRA syndrome, which could also have a favorable impact on the hemorrhagic mortality (non-published data); and
3. Treatment of the hyperfibrinolysis with an antifibrinolytic agent (tranexamic acid). It has been recently reported that APL cells present abnormally high levels of annexins (especially annexin II), and that these levels may provide the fundamental mechanism for the hemorrhagic complications in APL by increasing the production of t-PA dependent plasmin. These findings provide new reasons for the introduction of tranexamic acid in the hemorrhagic prophylaxis of APL.
Detailed Description:
Induction chemotherapy:
All-trans retinoic acid, will be administered by mouth (PO) from the first day at a dose of 45 mg/m²/day, fractionated into 2 doses.
In patients aged \< 20 years, the ATRA dose will be reduced to 25 mg/m²/day fractionated into 2 doses.
The treatment with ATRA will continue until a CR is achieved or for a maximum of 90 days in the case of persistence of atypical promyelocytes in the bone marrow.
Idarubicin, 12 mg/m² on days 2, 4, 6 and 8 of treatment by slow intravenous infusion (20 minutes).
In patients older than 70 years of age only 3 doses of idarubicin will be given on days 2, 4, and 6.
Supporting measures:
Prednisone, 0.5 mg/kg/day days 1 to 15. Tranexamic acid, 100 mg/kg/day in continuous perfusion, if platelets \< 50 x 10\^9/L or evident clinical-biological signs of coagulopathy. This treatment will be discontinued if the platelet counts are \> 50 x 10\^9/L.
Transfusion of platelet concentrates to keep up counts above 30 x 10\^9/L during the first 10 days and PRC to maintain hemoglobin levels greater than 9 g/dL.
Prophylactic heparin should not be used.
All-trans retinoic acid, will be administered by mouth (PO) from the first day at a dose of 45 mg/m²/day, fractionated into 2 doses.
In patients aged \< 20 years, the ATRA dose will be reduced to 25 mg/m²/day fractionated into 2 doses.
The treatment with ATRA will continue until a CR is achieved or for a maximum of 90 days in the case of persistence of atypical promyelocytes in the bone marrow.
Idarubicin, 12 mg/m² on days 2, 4, 6 and 8 of treatment by slow intravenous infusion (20 minutes).
In patients older than 70 years of age only 3 doses of idarubicin will be given on days 2, 4, and 6.
Supporting measures:
Prednisone, 0.5 mg/kg/day days 1 to 15. Tranexamic acid, 100 mg/kg/day in continuous perfusion, if platelets \< 50 x 10\^9/L or evident clinical-biological signs of coagulopathy. This treatment will be discontinued if the platelet counts are \> 50 x 10\^9/L.
Transfusion of platelet concentrates to keep up counts above 30 x 10\^9/L during the first 10 days and PRC to maintain hemoglobin levels greater than 9 g/dL.
Prophylactic heparin should not be used.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: