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

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

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

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Leukemia; Acute Disease; Nonlymphocytic Leukemia
• Intervention / Treatment: Drug: vosaroxin

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 Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • La Jolla, California, United States, 92037
      • Scripps Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Blood and Marrow Transplant Program
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • The University Of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46206
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46237
      • St. Francis Hospital & Health Systems at Beech Grove Campus
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center at Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65203
      • University of MO Ellis Fischel Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at The University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All Study Patients; 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; 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.; Other Names: voreloxin; SNS-595

What is the study measuring?

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
Overall Survival		2 years
Leukemia-free Survival (LFS)	The censor date was the last known alive date without report of relapse.	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

Collaborators and Investigators

• Sponsor: Sunesis Pharmaceuticals
• Investigators: Study Director: Adam Craig, MD, Sunesis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 23, 2009

Study Registration Dates

• First Submitted: January 23, 2008
• First Submitted That Met QC Criteria: January 23, 2008
• First Posted (Estimate): February 6, 2008

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Elderly; Cancer; Leukemia; Hematologic Diseases; Myelodysplastic Syndromes; Blood; Malignancy; Older; Hematologic; Myeloid; SNS-595; Sunesis; voreloxin; reveal-1
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Acute Disease
• Other Study ID Numbers: SPO-0014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified data of individual participants experiencing Serious Adverse Events