Ignite Creation Date:
2024-05-05 @ 6:30 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00495287
Status:
COMPLETED
Last Update Posted:
2016-03-31
First Post:
2007-07-02
Brief Title:
A Remission Induction Therapy and Risk-oriented Postremission Strategy for Adult Acute Myelogenous Leukemia AML
Sponsor:
Northern Italy Leukemia Group
Organization:
Northern Italy Leukemia Group
Study Overview
Official Title:
Phase III Trial in AML Comparing Standard-dose vs High-dose Remission Induction and Within a Risk-oriented Postremission Strategy Autologous Blood Stem Cell Transplantation vs Blood Stem Cell-supported Multicycle High-dose Program
Status:
COMPLETED
Status Verified Date:
2016-03
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 study was set up to assess
1 Standard-dose versus high-dose remission induction therapy A standard ICE chemotherapy vs sequential high-dose cytarabine with appropriate supportiveprophylactic measures followed by morphological cytogenetic and molecular monitoring of remission
2 A risk-oriented postremission therapy HR patients will be electively submitted to allogeneic stem cell transplantation allo-SCT whenever possible relatedunrelated donorcord blood ablativenon-ablative conditioning according to national and local protocols and guidelines Provided sufficient blood stem cells were previously collected 2x10e6kg Cluster of Differentiation 34 cells SR patients and HR patients excluded from allo-SCT and aged 65 years or less will be randomized to myeloablative autologous blood stem cell transplantation vs non-myeloablative multicycle autologous blood stem cell-supported high-dose cytarabine-based therapy
HRSR patients unable to be randomized because of inadequate blood stem cell yield will receive intermediate-dose consolidation patients aged 65 years will be treated with age-adapted therapy
1 Standard-dose versus high-dose remission induction therapy A standard ICE chemotherapy vs sequential high-dose cytarabine with appropriate supportiveprophylactic measures followed by morphological cytogenetic and molecular monitoring of remission
2 A risk-oriented postremission therapy HR patients will be electively submitted to allogeneic stem cell transplantation allo-SCT whenever possible relatedunrelated donorcord blood ablativenon-ablative conditioning according to national and local protocols and guidelines Provided sufficient blood stem cells were previously collected 2x10e6kg Cluster of Differentiation 34 cells SR patients and HR patients excluded from allo-SCT and aged 65 years or less will be randomized to myeloablative autologous blood stem cell transplantation vs non-myeloablative multicycle autologous blood stem cell-supported high-dose cytarabine-based therapy
HRSR patients unable to be randomized because of inadequate blood stem cell yield will receive intermediate-dose consolidation patients aged 65 years will be treated with age-adapted therapy
Detailed Description:
Adult AML is a difficult-to-treat illness because of both biological and therapeutic reasons Most patients are aged 50 years andor present with comorbid conditions andor display high-risk AML-related features poor risk cytogenetics prior myelodysplasia secondary AML This results in unsatisfactory response to conventional first-line therapy and makes it difficult to apply the most effective post-remission consolidation options allo-SCT in younger patients with HR features autologous blood stem cell transplantation and high-dose cytarabine-based therapy in the remainder
In a prior phase II uncontrolled NILG trial registered NCT 00400637a two-step increasing intensity induction was adopted in order to optimize induction results 51 of ICE-refractory cases responded to the salvage regimen irrespective of risk class In the same study all HR patients had to be sent to allografting whereas SR patients by clinico-cytogenetics criteria were to receive up to three high-dose cytarabine-based cycles each one supported by a fixed amount of autologous blood-stem cells 1-2x10e6kg Cluster of Differentiation 34 cells cells to minimize the risks of high-dose cytarabine-related myelosuppression and to increase treatment intensity by reducing intercycle delays DFS was 41 at 5 years 58 in SR patients aged 55 years 47 in SR patients aged 55 years and 47 in HR patients with an identifiable donor No treatment-related death occurred during the pancytopenic phase in 118 patients receiving 299 blood stem-cell supported high-dose cytarabine cycles
These facts led to the present trial in which 1 high-dose induction formerly used as salvage is directly compared to standard ICE chemotherapy and 2 the blood-stem cell supported multicycle high-dose cytarabine program is directly compared to a standard autologous blood stem cell transplantation
RANDOM 1 CYCLE 1
Standard ICE all drugs by IV route idarubicin 12 mgm2d on dd 1-3 cytarabine 100 mgm2bd on dd 1-7 etoposide 100 mgm2d on dd 1-5 G-CSF from d 11
High-dose sequential all drugs by IV route cytarabine 2 gm2bd on dd 1-2 and 8-9 idarubicin 18 mgm2d on dd 3 and 10 G-Colony Stimulating Factory G-CSF from d 11 1 gm2 in frail patients aged 60-65 and in all those aged 65 years
CYCLE 2 if CR achieved after cycle 1 Standard IC idarubicin 10 mgm2d on dd 1-3 cytarabine 100 mgm2bd on dd 1-7 G-CSF
CYCLE 3 Intermediate-dose cytarabine 1 gm2bd on dd 1-4 followed by G-CSF and by stem cell collection 1-2x10e6kg CD34 cells in three separate bags
ALLO-SCT Allogeneic Stem Cells Transplantation All HR patients are eligible to allo-SCT as first therapeutic option Allo-SCT procedure any type according to local protocolsguidelines
RANDOM 2
All SR patients and HR ones excluded from allo-SCT
Autologous blood stem cell transplantation after BU-CY2 regimen Busulfan 08 mgkg IV on dd -8 to -5 Cy 60 mgkgd on dd -4 to -3 autograft on d 0 2-6x10e6kg CD34 cells and G-CSF from d 1
Autologous blood stem cell supported multicycle therapy x3 monthly with cytarabine 2 gm2bd on dd 1-5 idarubicin 8 mgm2d on dd 1-2 autograft on d 6 1-2x10e6kg CD34 cells and G-CSF from d 8
Patients excluded from Random 2 as well as from allo-SCT receive attenuated unsupported consolidation with 1-2 intermediate-dose cytarabine cycles Patients aged 65 years are excluded from Random 2
RISK CLASSIFICATION Cytogenetic risk classification is based on MRCECOG-SWOGCALGB criteria cytogenetic risk classes favorable normalintermediate unfavorable other unknown clinical risk classification is based on selected diagnostic criteria and response to chemotherapy cycle 1 The final risk model integrates cytogenetic and clinical risk to encompass two broad risk classes SR and HR
Standard risk SR favorable cytogenetics CR achieved after cycle 1 or normalintermediate cytogenetics CR achieved after cycle 1 lack of high-risk characteristics
High risk HR unfavorable cytogenetics or normalintermediate cytogenetics with any high-risk characteristic WBC 50x10e9lFAB M067 or corresponding WHO secondary AML Myelodysplastic Syndrome MDS-associated AML hepatosplenomegaly FLT3 mutation CR not achieved with cycle persistent cytogenetic abnormality at CR or otherunknown cytogenetics
In a prior phase II uncontrolled NILG trial registered NCT 00400637a two-step increasing intensity induction was adopted in order to optimize induction results 51 of ICE-refractory cases responded to the salvage regimen irrespective of risk class In the same study all HR patients had to be sent to allografting whereas SR patients by clinico-cytogenetics criteria were to receive up to three high-dose cytarabine-based cycles each one supported by a fixed amount of autologous blood-stem cells 1-2x10e6kg Cluster of Differentiation 34 cells cells to minimize the risks of high-dose cytarabine-related myelosuppression and to increase treatment intensity by reducing intercycle delays DFS was 41 at 5 years 58 in SR patients aged 55 years 47 in SR patients aged 55 years and 47 in HR patients with an identifiable donor No treatment-related death occurred during the pancytopenic phase in 118 patients receiving 299 blood stem-cell supported high-dose cytarabine cycles
These facts led to the present trial in which 1 high-dose induction formerly used as salvage is directly compared to standard ICE chemotherapy and 2 the blood-stem cell supported multicycle high-dose cytarabine program is directly compared to a standard autologous blood stem cell transplantation
RANDOM 1 CYCLE 1
Standard ICE all drugs by IV route idarubicin 12 mgm2d on dd 1-3 cytarabine 100 mgm2bd on dd 1-7 etoposide 100 mgm2d on dd 1-5 G-CSF from d 11
High-dose sequential all drugs by IV route cytarabine 2 gm2bd on dd 1-2 and 8-9 idarubicin 18 mgm2d on dd 3 and 10 G-Colony Stimulating Factory G-CSF from d 11 1 gm2 in frail patients aged 60-65 and in all those aged 65 years
CYCLE 2 if CR achieved after cycle 1 Standard IC idarubicin 10 mgm2d on dd 1-3 cytarabine 100 mgm2bd on dd 1-7 G-CSF
CYCLE 3 Intermediate-dose cytarabine 1 gm2bd on dd 1-4 followed by G-CSF and by stem cell collection 1-2x10e6kg CD34 cells in three separate bags
ALLO-SCT Allogeneic Stem Cells Transplantation All HR patients are eligible to allo-SCT as first therapeutic option Allo-SCT procedure any type according to local protocolsguidelines
RANDOM 2
All SR patients and HR ones excluded from allo-SCT
Autologous blood stem cell transplantation after BU-CY2 regimen Busulfan 08 mgkg IV on dd -8 to -5 Cy 60 mgkgd on dd -4 to -3 autograft on d 0 2-6x10e6kg CD34 cells and G-CSF from d 1
Autologous blood stem cell supported multicycle therapy x3 monthly with cytarabine 2 gm2bd on dd 1-5 idarubicin 8 mgm2d on dd 1-2 autograft on d 6 1-2x10e6kg CD34 cells and G-CSF from d 8
Patients excluded from Random 2 as well as from allo-SCT receive attenuated unsupported consolidation with 1-2 intermediate-dose cytarabine cycles Patients aged 65 years are excluded from Random 2
RISK CLASSIFICATION Cytogenetic risk classification is based on MRCECOG-SWOGCALGB criteria cytogenetic risk classes favorable normalintermediate unfavorable other unknown clinical risk classification is based on selected diagnostic criteria and response to chemotherapy cycle 1 The final risk model integrates cytogenetic and clinical risk to encompass two broad risk classes SR and HR
Standard risk SR favorable cytogenetics CR achieved after cycle 1 or normalintermediate cytogenetics CR achieved after cycle 1 lack of high-risk characteristics
High risk HR unfavorable cytogenetics or normalintermediate cytogenetics with any high-risk characteristic WBC 50x10e9lFAB M067 or corresponding WHO secondary AML Myelodysplastic Syndrome MDS-associated AML hepatosplenomegaly FLT3 mutation CR not achieved with cycle persistent cytogenetic abnormality at CR or otherunknown cytogenetics
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