Study of Voreloxin (Vosaroxin) in Older Patients With Untreated Acute Myeloid Leukemia
Primary Purpose
Leukemia, Acute Disease, Acute Myeloid Leukemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
vosaroxin
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring Leukemia, Myeloid, Elderly, Hematologic, Blood, Cancer, Malignancy, SNS-595, Sunesis, Hematologic Diseases, Myelodysplastic Syndromes, Older, voreloxin, reveal-1
Eligibility Criteria
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)
Sites / Locations
- Mayo Clinic Hospital
- Mayo Clinic Scottsdale
- Scripps Cancer Center
- Rocky Mountain Blood and Marrow Transplant Program
- Rush University Medical Center
- The University of Chicago
- Indiana University Cancer Center
- St. Francis Hospital & Health Systems at Beech Grove Campus
- Cancer Center of Kansas
- Cancer Center of Kansas
- LSU Health Sciences Center at Shreveport
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- University of Mississippi Medical Center
- University of MO Ellis Fischel Cancer Center
- University of Pittsburgh Cancer Institute
- Hollings Cancer Center at Medical University of South Carolina
- Vanderbilt-Ingram Cancer Center
- MD Anderson Cancer Center
- Huntsman Cancer Institute at the University of Utah
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All Study Patients
Arm Description
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Leukemia-free Survival (LFS)
The censor date was the last known alive date without report of relapse.
Overall Survival
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.
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.
All Cause Mortality
Mortality of those patients enrolled in the study and receiving intervention
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00607997
Brief Title
Study of Voreloxin (Vosaroxin) in Older Patients With Untreated Acute Myeloid Leukemia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
May 15, 2008 (Actual)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 23, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunesis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Disease, Acute Myeloid Leukemia, Nonlymphocytic Leukemia, Myelodysplastic Syndromes
Keywords
Leukemia, Myeloid, Elderly, Hematologic, Blood, Cancer, Malignancy, SNS-595, Sunesis, Hematologic Diseases, Myelodysplastic Syndromes, Older, voreloxin, reveal-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
113 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All Study Patients
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
vosaroxin
Other Intervention Name(s)
voreloxin, SNS-595
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Leukemia-free Survival (LFS)
Description
The censor date was the last known alive date without report of relapse.
Time Frame
2 years
Title
Overall Survival
Time Frame
2 years
Title
Pharmacokinetics Day 1 - Cmax (ng/mL)
Description
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.
Time Frame
1 Day
Title
Pharmacokinetics Day 4 Cmax (ng/mL)
Description
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.
Time Frame
Day 4
Title
All Cause Mortality
Description
Mortality of those patients enrolled in the study and receiving intervention
Time Frame
30 and 60 days
Title
Pharmacokinetics Day 1 - AUC0-72 and AUCinf (hr*ng/mL)
Description
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.
Time Frame
1 Day
Title
Pharmacokinetics Day 1 - t1/2 (hr) and MRTinf (hr)
Description
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.
Time Frame
1 Day
Title
Pharmacokinetics Day 1 - CL (L/hr)
Description
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.
Time Frame
1 Day
Title
Pharmacokinetics Day 1 - Vss (L)
Description
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.
Time Frame
1 Day
Title
Pharmacokinetics Day 4 - AUC0-72 and AUCinf (hr*ng/mL)
Description
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.
Time Frame
Day 4
Title
Pharmacokinetics Day 4 - t1/2 (hr) and MRTinf (hr)
Description
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.
Time Frame
Day 4
Title
Pharmacokinetics Day 4 - CL (L/hr)
Description
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.
Time Frame
Day 4
Title
Pharmacokinetics Day 4 - Vss (L)
Description
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.
Time Frame
Day 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam Craig, MD
Organizational Affiliation
Sunesis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Mayo Clinic Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Scripps Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Rocky Mountain Blood and Marrow Transplant Program
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46206
Country
United States
Facility Name
St. Francis Hospital & Health Systems at Beech Grove Campus
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67208
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
LSU Health Sciences Center at Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
University of MO Ellis Fischel Cancer Center
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65203
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Hollings Cancer Center at Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Huntsman Cancer Institute at the University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified data of individual participants experiencing Serious Adverse Events
Citations:
PubMed Identifier
25403830
Citation
Stuart RK, Cripe LD, Maris MB, Cooper MA, Stone RM, Dakhil SR, Turturro F, Stock W, Mason J, Shami PJ, Strickland SA, Costa LJ, Borthakur G, Michelson GC, Fox JA, Leavitt RD, Ravandi F. REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia. Br J Haematol. 2015 Mar;168(6):796-805. doi: 10.1111/bjh.13214. Epub 2014 Nov 17.
Results Reference
derived
Learn more about this trial
Study of Voreloxin (Vosaroxin) in Older Patients With Untreated Acute Myeloid Leukemia
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