Study of Voreloxin (Vosaroxin) in Older Patients With Untreated Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This study will evaluate the overall remission rate of treatment with vosaroxin (formerly voreloxin) Injection in patients at least 60 years of age with previously untreated AML

Detailed Description
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Other objectives of this study include: Assess the safety of treatment with vosaroxin, including the 30 and 60 day all-cause mortality Assess leukemia free survival (LFS), event-free survival (EFS), overall survival (OS), and duration of remission (DR). Characterize the pharmacokinetic (PK) profile of vosaroxin in this patient population. Evaluate potential stratification biomarkers by evaluating DNA-damage and apoptotic pathways in bone marrow samples before and after treatment with vosaroxin

Official Title
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A Phase 2, Open-Label, Multicenter Clinical Study of the Safety and Efficacy of Voreloxin (Vosaroxin) Injection in Patients Equal to or Greater Than 60 Years of Age With Previously Untreated Acute Myeloid Leukemia

Conditions
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Leukemia, Acute Disease, Acute Myeloid Leukemia, Nonlymphocytic Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: vosaroxin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: At least 60 years of age and diagnosis of previously untreated AML (either de novo or from an antecedent hematologic disorder or therapy related AML) At least 20% blasts by BM biopsy or aspirate ECOG performance status of 0,1,or 2 Adequate cardiac, renal and liver function Key Exclusion Criteria: Uncontrolled DIC Active central nervous system involvement by AML Requiring hemodialysis or peritoneal dialysis Some prior history of heart attack or stroke (depending on how long ago the event occurred)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Study Patients<br>Schedule A: 72 mg/m2 vosaroxin Days 1, 8 and 15 Schedule B: 72 mg/m2 vosaroxin on Days 1 and 8 Schedule C: 72 mg/m2 on Days 1 and 4, or Schedule C: 90 mg/m2 on Days 1 and 4 | Drug: vosaroxin<br>* Vosaroxin was administered by slow intravenous (IV) infusion or via syringe pump within 10 minutes.Patients could have completed up to 4 treatment cycles consisting of 1 or 2 induction treatment cycles and up to 2 consolidation treatment cycles. For Schedule A, an induction cycle was a minimum of 21 days during which patients received vosaroxin on Days 1, 8, and 15, followed by weekly observations until hematologic recovery for patients with aplastic marrow after the postinduction bone marrow assessment. For Schedules B and C, an induction cycle was a minimum of 15 days, during which patients received vosaroxin on Days 1 and 8 (Schedule B), or Days 1 and 4 (Schedule C), followed by the same weekly observations until hematologic recovery as for Schedule A.<br>* Other names: SNS-595;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission Rate Defined as the Percentage of Patients Whose Respnse is CR or CRp Based on International Working Group (IWG) Response Criteria and Treatment Outcomes Definitions | Combined remission rate (complete remission [CR] + complete remission with incomplete platelet recovery [CRp]) of vosaroxin of patients ≥ 60 years old with previously untreated (de novo or secondary) AML are presented by treatment group for all treated analysis set. Per IWG criteria, a CR requires bone marrow blasts < 5%, absolute neutrophil count (ANC) > 1000 cells/uL, and platelet (plt) count > 100,000 plt/uL. The criteria for CRp are the same as those for CR, except for platelet count <= 100,000 lt/uL. Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (Morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukemia-free Survival (LFS) | The censor date was the last known alive date without report of relapse. | 2 years | 
| Overall Survival |  | 2 years | 
| Pharmacokinetics Day 1 - Cmax (ng/mL) | Pharmacokinetic Parameters (Cmax) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | 1 Day | 
| Pharmacokinetics Day 4 Cmax (ng/mL) | Pharmacokinetic Parameters by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) on Day 4 Please note that N, mean and CV% are reported, but CV% is not an option in the drop down menu. So Standard Deviation is really CV% in the table. | Day 4 | 
| All Cause Mortality | Mortality of those patients enrolled in the study and receiving intervention | 30 and 60 days | 
| Pharmacokinetics Day 1 - AUC0-72 and AUCinf (hr*ng/mL) | Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | 1 Day | 
| Pharmacokinetics Day 1 - t1/2 (hr) and MRTinf (hr) | Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | 1 Day | 
| Pharmacokinetics Day 1 - CL (L/hr) | Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | 1 Day | 
| Pharmacokinetics Day 1 - Vss (L) | Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 1 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | 1 Day | 
| Pharmacokinetics Day 4 - AUC0-72 and AUCinf (hr*ng/mL) | Pharmacokinetic Parameters (AUC0-72 and AUCinf ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. Standard Deviation is really CV% in the table. | Day 4 | 
| Pharmacokinetics Day 4 - t1/2 (hr) and MRTinf (hr) | Pharmacokinetic Parameters (t1/2 and and MRTinf) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The Standard Deviation is really CV% in the table. | Day 4 | 
| Pharmacokinetics Day 4 - CL (L/hr) | Pharmacokinetic Parameters (CL) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | Day 4 | 
| Pharmacokinetics Day 4 - Vss (L) | Pharmacokinetic Parameters (Vss ) by Schedule, Dosing Day, and Dose Cohort for Patients Treated With Vosaroxin as a Single Agent (SPO 0014) for Day 4 Numbers reported are N, mean and CV%. Please note CV% is not a choice that can be entered from the drop down menu. The standard deviation is really CV% in the table. | Day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Myeloid, Elderly, Hematologic, Blood, Cancer, Malignancy, SNS-595, Sunesis, Hematologic Diseases, Myelodysplastic Syndromes, Older, voreloxin, reveal-1