Ignite Creation Date:
2024-05-06 @ 6:15 PM
Last Modification Date:
2024-10-26 @ 2:44 PM
Study NCT ID:
NCT05599360
Status:
RECRUITING
Last Update Posted:
2022-10-31
First Post:
2022-01-20
Brief Title:
Vyxeos for Induction of Low- or Intermediate-risk
Sponsor:
Shaare Zedek Medical Center
Organization:
Shaare Zedek Medical Center
Study Overview
Official Title:
Vyxeos for Induction of Newly Diagnosed Low- or Intermediate-risk AML Patients Age 18-70 A Pilot Study
Status:
RECRUITING
Status Verified Date:
2022-10
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:
Vyxeos Vyxeos is a liposomal-encapsulated combination of cytarabine and daunorubicin at a molar ratio of 51 Delivery of the 51 molar ratio seems to prevent antagonistic drug-drug interactions and the liposomal encapsulation increases the plasma half-life of cytarabine and daunorubicin and leads to drug accumulation within the bone marrow BM
Despite previous results that highlighted the advantage of Vyxeos for sAML it is intuitively likely that this powerful drug is also suitable for non-sAML The mechanism of action is relevant for every AML Following the FDA approval of the drug for sAML we would like to evaluate its efficacy for low or intermediate risk fms-like tyrosine kinase 3 FLT3-negative de novo AML patients This consideration is particularly relevant by the inclusion of young AML patients in the study
Gemtuzumab ozogamicin GO Gemtuzumab ozogamicin Mylotarg - an anti-cluster of differentiation 33 CD33 monoclonal antibody linked to calicheamicin was approved for the treatment of newly diagnosed AML patients when given as a combination with the 73 regimen
One of the goals of the current study is to examine the feasibility and efficacy of the combination of Mylotarg plus Vyxeos
Minimal measurable residual disease MRD Minimal or measurable residual disease MRD denotes the presence of leukemia cells down to levels of 110-4 to 110-6 compared with 120 in morphology-based assessments MRD can be evaluated using a variety of multiparameter flow cytometry MFC and molecular methods There are no data regarding the achievement or impact of MRD using Vyxeos as induction therapy The current trial will address this issue
Purpose of this Trial The current study is designed to examine the response rate of the Vyxeos as induction therapy for newly diagnosed lowintermediate risk AML patients in the real world setting Patients will receive the same induction therapy that they were to receive had they not entered this study cytarabine daunorubicin Mylotarg but the combination of cytarabine daunorubicin will be given in the unique formulation of Vyxeos In addition to classic CRCRi evaluation MFC MRD evaluation using an centralized internationally recognized laboratory will be done at the end of induction In addition this pilot study will also provide clinical safety information about the combination of Vyxeos with Mylotarg
Despite previous results that highlighted the advantage of Vyxeos for sAML it is intuitively likely that this powerful drug is also suitable for non-sAML The mechanism of action is relevant for every AML Following the FDA approval of the drug for sAML we would like to evaluate its efficacy for low or intermediate risk fms-like tyrosine kinase 3 FLT3-negative de novo AML patients This consideration is particularly relevant by the inclusion of young AML patients in the study
Gemtuzumab ozogamicin GO Gemtuzumab ozogamicin Mylotarg - an anti-cluster of differentiation 33 CD33 monoclonal antibody linked to calicheamicin was approved for the treatment of newly diagnosed AML patients when given as a combination with the 73 regimen
One of the goals of the current study is to examine the feasibility and efficacy of the combination of Mylotarg plus Vyxeos
Minimal measurable residual disease MRD Minimal or measurable residual disease MRD denotes the presence of leukemia cells down to levels of 110-4 to 110-6 compared with 120 in morphology-based assessments MRD can be evaluated using a variety of multiparameter flow cytometry MFC and molecular methods There are no data regarding the achievement or impact of MRD using Vyxeos as induction therapy The current trial will address this issue
Purpose of this Trial The current study is designed to examine the response rate of the Vyxeos as induction therapy for newly diagnosed lowintermediate risk AML patients in the real world setting Patients will receive the same induction therapy that they were to receive had they not entered this study cytarabine daunorubicin Mylotarg but the combination of cytarabine daunorubicin will be given in the unique formulation of Vyxeos In addition to classic CRCRi evaluation MFC MRD evaluation using an centralized internationally recognized laboratory will be done at the end of induction In addition this pilot study will also provide clinical safety information about the combination of Vyxeos with Mylotarg
Detailed Description:
Introduction Induction therapy Currently most physicians treating fit patients with acute myeloid leukemia AML employ an anthracycline plus cytarabine 73 regimen as induction therapy In the past few years 2 new drugs were approved as adjuncts to the 73 regimen for treatment of fit patients Midostaurin- a FLT3 inhibitor and gemtuzumab ozogamicin- an anti-CD33 monoclonal antibody linked to chemotherapy It has been postulated that using the same drugs as in the 73 regimen but at a fixed molar ratio of cytarabine and daunorubicin will increase the CR rate and improve minimal residual disease and disease free survival DFS
Vyxeos
Vyxeos is a liposomal-encapsulated combination of cytarabine and daunorubicin at a molar ratio of 51 Delivery of the 51 molar ratio seems to prevent antagonistic drug-drug interactions and the liposomal encapsulation increases the plasma half-life of cytarabine and daunorubicin and leads to drug accumulation within the bone marrow BM Two randomized controlled trials have been reported in newly diagnosed AML patients
A phase II multicenter randomized open-label trial studied the efficacy and safety of Vyxeos among newly diagnosed AML patients age 60-75 The study compared 1-2 induction courses of Vyxeos with 73 daunorubicin dose of 45-60 mgm2 Patients were allowed to receive 1-2 consolidation courses of Vyxeos in the investigational arm and low dose cytarabine withwithout daunorubicin or intermediate dose cytarabine in the control arm The primary end-point was defined as response rate complete remission CR CR with incomplete hematologic recovery CRi 127 patients were enrolled and randomized in 21 ratio The study showed an increased response rate CRCRi of 667 vs 512 in the investigational arm but without statistical significance p07 A planned sub-group analysis of secondary AML sAML patients revealed a more impressive still non-significant response rate advantage to the Vyxeos patients 576 vs 316 p06 but with significant overall survival OS superiority median 121 vs 61 months HR 046 p01
The phase III trial was an open-labeled randomized trial that enrolled only sAML patients age 60-75 with the exception of patients with antecedent myeloproliferative neoplasm Patients received 2-3 cycles 1-2 induction courses and 1 consolidation of either 73 with daunorubicin 60 mgm2 or Vyxeos The primary end-point was defined as OS A total of 309 patients were enrolled and randomized in a 11 ratio This study showed a significant OS median of 956 vs 595 months HR069 p005 and CRCRi rate 477 vs 333 p016 advantage for the patients who received the Vyxeos These results led the Food and Drug Administration FDA in August 2017 to approve the drug for use in the treatment of newly diagnosed therapy-related AML tAML and AML with myelodysplasia-related changes MRC
Despite the results that highlighted the advantage of Vyxeos for sAML it is intuitively likely that this powerful drug is also suitable for non-sAML The mechanism of action is relevant for every AML Following the FDA approval of the drug for sAML we would like to evaluate its efficacy for low or intermediate risk FLT3-negative de novo AML patients This consideration is particularly relevant by the inclusion of young AML patients in the study
Gemtuzumab ozogamicin GO Gemtuzumab ozogamicin Mylotarg - an anti-CD33 monoclonal antibody linked to calicheamicin was approved for the treatment of newly diagnosed AML patients when given as a combination with the 73 regimen
The French Alfa-0701 study evaluated the safety and efficacy of GO administered in a fractionated dosing regimen 3 mgm² administered on Days 1 4 and 7 when added to the standard 73 regimen Patients with a CR or CR with incomplete platelet recovery CRp received consolidation therapy with 2 courses of treatment including daunorubicin plus cytarabine with or without GO based on their initial randomization The primary end point was event free survival EFS which was longer in the GO arm median of 173 months 95 combination index CI 134-300 vs 95 months 95 CI 81-120 3-years EFS was achieved by 398 of the GO arm compared to 136 of the control arm OS was better in the GO arm 275 vs 218 months but have not reached statistical significance HR 0807 95 CI 0596-1093 p016465 A meta-analysis of GO in combination with chemotherapy for newly diagnosed AML patients concluded that GO does not increase the CR rate but decreases the relapse rate and improves the OS The drug is ineffective in high risk patients
One of the goals of the current study is to examine the feasibility and efficacy of the combination of Mylotarg plus Vyxeos
Minimal measurable residual disease MRD Several factors present at diagnosis of AML including cytogenetics molecular genetics and age have been associated with prognosis Increasing evidence now indicates that the ability to identify residual disease far below the morphology-based 5 blast threshold is an important tool for refining the approach to risk classification Minimal or measurable residual disease MRD denotes the presence of leukemia cells down to levels of 110-4 to 110-6 compared with 120 in morphology-based assessments MRD can be evaluated using a variety of multiparameter flow cytometry MFC and molecular methods There are no data regarding the achievement or impact of MRD using Vyxeos as induction therapy The current trial will address this issue
Purpose of this Trial The current study is designed to examine the response rate of the Vyxeos as induction therapy for newly diagnosed lowintermediate risk AML patients in the real world setting Patients will receive the same induction therapy that they were to receive had they not entered this study cytarabine daunorubicin Mylotarg but the combination of cytarabine daunorubicin will be given in the unique formulation of Vyxeos In addition to classic CRCRi evaluation MFC MRD evaluation using an centralized internationally recognized laboratory will be done at the end of induction In addition this pilot study will also provide clinical safety information about the combination of Vyxeos with Mylotarg
Gender and Ethnicity Entry to this study is open to both men and women and to persons of any racial or ethnic group We are aware of no data that would lead us to expect differential treatment effects by gender and ethnicity and therefore have not incorporated separate accrual goals for these subgroups
Vyxeos
Vyxeos is a liposomal-encapsulated combination of cytarabine and daunorubicin at a molar ratio of 51 Delivery of the 51 molar ratio seems to prevent antagonistic drug-drug interactions and the liposomal encapsulation increases the plasma half-life of cytarabine and daunorubicin and leads to drug accumulation within the bone marrow BM Two randomized controlled trials have been reported in newly diagnosed AML patients
A phase II multicenter randomized open-label trial studied the efficacy and safety of Vyxeos among newly diagnosed AML patients age 60-75 The study compared 1-2 induction courses of Vyxeos with 73 daunorubicin dose of 45-60 mgm2 Patients were allowed to receive 1-2 consolidation courses of Vyxeos in the investigational arm and low dose cytarabine withwithout daunorubicin or intermediate dose cytarabine in the control arm The primary end-point was defined as response rate complete remission CR CR with incomplete hematologic recovery CRi 127 patients were enrolled and randomized in 21 ratio The study showed an increased response rate CRCRi of 667 vs 512 in the investigational arm but without statistical significance p07 A planned sub-group analysis of secondary AML sAML patients revealed a more impressive still non-significant response rate advantage to the Vyxeos patients 576 vs 316 p06 but with significant overall survival OS superiority median 121 vs 61 months HR 046 p01
The phase III trial was an open-labeled randomized trial that enrolled only sAML patients age 60-75 with the exception of patients with antecedent myeloproliferative neoplasm Patients received 2-3 cycles 1-2 induction courses and 1 consolidation of either 73 with daunorubicin 60 mgm2 or Vyxeos The primary end-point was defined as OS A total of 309 patients were enrolled and randomized in a 11 ratio This study showed a significant OS median of 956 vs 595 months HR069 p005 and CRCRi rate 477 vs 333 p016 advantage for the patients who received the Vyxeos These results led the Food and Drug Administration FDA in August 2017 to approve the drug for use in the treatment of newly diagnosed therapy-related AML tAML and AML with myelodysplasia-related changes MRC
Despite the results that highlighted the advantage of Vyxeos for sAML it is intuitively likely that this powerful drug is also suitable for non-sAML The mechanism of action is relevant for every AML Following the FDA approval of the drug for sAML we would like to evaluate its efficacy for low or intermediate risk FLT3-negative de novo AML patients This consideration is particularly relevant by the inclusion of young AML patients in the study
Gemtuzumab ozogamicin GO Gemtuzumab ozogamicin Mylotarg - an anti-CD33 monoclonal antibody linked to calicheamicin was approved for the treatment of newly diagnosed AML patients when given as a combination with the 73 regimen
The French Alfa-0701 study evaluated the safety and efficacy of GO administered in a fractionated dosing regimen 3 mgm² administered on Days 1 4 and 7 when added to the standard 73 regimen Patients with a CR or CR with incomplete platelet recovery CRp received consolidation therapy with 2 courses of treatment including daunorubicin plus cytarabine with or without GO based on their initial randomization The primary end point was event free survival EFS which was longer in the GO arm median of 173 months 95 combination index CI 134-300 vs 95 months 95 CI 81-120 3-years EFS was achieved by 398 of the GO arm compared to 136 of the control arm OS was better in the GO arm 275 vs 218 months but have not reached statistical significance HR 0807 95 CI 0596-1093 p016465 A meta-analysis of GO in combination with chemotherapy for newly diagnosed AML patients concluded that GO does not increase the CR rate but decreases the relapse rate and improves the OS The drug is ineffective in high risk patients
One of the goals of the current study is to examine the feasibility and efficacy of the combination of Mylotarg plus Vyxeos
Minimal measurable residual disease MRD Several factors present at diagnosis of AML including cytogenetics molecular genetics and age have been associated with prognosis Increasing evidence now indicates that the ability to identify residual disease far below the morphology-based 5 blast threshold is an important tool for refining the approach to risk classification Minimal or measurable residual disease MRD denotes the presence of leukemia cells down to levels of 110-4 to 110-6 compared with 120 in morphology-based assessments MRD can be evaluated using a variety of multiparameter flow cytometry MFC and molecular methods There are no data regarding the achievement or impact of MRD using Vyxeos as induction therapy The current trial will address this issue
Purpose of this Trial The current study is designed to examine the response rate of the Vyxeos as induction therapy for newly diagnosed lowintermediate risk AML patients in the real world setting Patients will receive the same induction therapy that they were to receive had they not entered this study cytarabine daunorubicin Mylotarg but the combination of cytarabine daunorubicin will be given in the unique formulation of Vyxeos In addition to classic CRCRi evaluation MFC MRD evaluation using an centralized internationally recognized laboratory will be done at the end of induction In addition this pilot study will also provide clinical safety information about the combination of Vyxeos with Mylotarg
Gender and Ethnicity Entry to this study is open to both men and women and to persons of any racial or ethnic group We are aware of no data that would lead us to expect differential treatment effects by gender and ethnicity and therefore have not incorporated separate accrual goals for these subgroups
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None