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

Phase 2

Completed

• Conditions: Leukemia; Acute Disease; Myelodysplastic Syndromes; Acute Myeloid Leukemia; Nonlymphocytic Leukemia
• Interventions: Drug: vosaroxin

• Registration Number: NCT00607997
• Lead Sponsor: Sunesis Pharmaceuticals

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:

1. Assess the safety of treatment with vosaroxin, including the 30 and 60 day all-cause mortality

2. Assess leukemia free survival (LFS), event-free survival (EFS), overall survival (OS), and duration of remission (DR).

3. Characterize the pharmacokinetic (PK) profile of vosaroxin in this patient population.

4. Evaluate potential stratification biomarkers by evaluating DNA-damage and apoptotic pathways in bone marrow samples before and after treatment with vosaroxin

Study Timeline

• Study First Submitted: 2008-01-23
• Study First Submitted QC: 2008-01-23
• Study First Posted: 2008-02-06
• Study Start: 2008-05-15
• Primary Completion: 2009-11
• Study Completion: 2009-11-23
• Results First Submitted: 2017-03-27
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-25
• Last Update Submitted: 2017-05-25
• Results First Posted: 2017-06-28
• Last Update Posted: 2017-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 113

Inclusion Criteria

1. 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)
2. At least 20% blasts by BM biopsy or aspirate
3. ECOG performance status of 0,1,or 2
4. Adequate cardiac, renal and liver function

Key

Exclusion Criteria

1. Uncontrolled DIC
2. Active central nervous system involvement by AML
3. Requiring hemodialysis or peritoneal dialysis
4. Some prior history of heart attack or stroke (depending on how long ago the event occurred)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All Study Patients	vosaroxin	* 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

Primary Outcome Measures

Name	Time	Method
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	2 years	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

Name	Time	Method
Leukemia-free Survival (LFS)	2 years	The censor date was the last known alive date without report of relapse.
Overall Survival	2 years
Pharmacokinetics Day 1 - Cmax (ng/mL)	1 Day	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)	Day 4	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	30 and 60 days	Mortality of those patients enrolled in the study and receiving intervention
Pharmacokinetics Day 1 - AUC0-72 and AUCinf (hr*ng/mL)	1 Day	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)	1 Day	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)	1 Day	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)	1 Day	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)	Day 4	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)	Day 4	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)	Day 4	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)	Day 4	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.

Trial Locations

Locations (19)

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

University of MO Ellis Fischel Cancer Center; 🇺🇸 Columbia, Missouri, United States

University of Pittsburgh Cancer Institute; 🇺🇸 Pittsburgh, Pennsylvania, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

St. Francis Hospital & Health Systems at Beech Grove Campus; 🇺🇸 Indianapolis, Indiana, United States

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Scripps Cancer Center; 🇺🇸 La Jolla, California, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

The University of Chicago; 🇺🇸 Chicago, Illinois, United States

Hollings Cancer Center at Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Cancer Center of Kansas; 🇺🇸 Wichita, Kansas, United States

Rocky Mountain Blood and Marrow Transplant Program; 🇺🇸 Denver, Colorado, United States

Indiana University Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Huntsman Cancer Institute at the University of Utah; 🇺🇸 Salt Lake City, Utah, United States

LSU Health Sciences Center at Shreveport; 🇺🇸 Shreveport, Louisiana, United States