search
Back to results

Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Voreloxin injection and cytarabine
Sponsored by
Sunesis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Leukemia, Acute Myeloid, Relapsed, Refractory, Cancer, AML, Cytarabine, SNS-595, Phase 1, Voreloxin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

KEY INCLUSION CRITERIA

  1. Relapsed or refractory AML subtypes defined by WHO, except acute promyelocytic leukemia. Relapsed/refractory disease may be de novo AML or secondary AML
  2. Treated with one to threee induction/reinduction AML regimens, prior induction or consolidation therapy with cytarabine allowed
  3. At least 10% blasts by BM biopsy or aspirate
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  5. Clinical laboratory values of a) Serum creatinine ≤1.5 mg/dL and calculated or measured creatinine clearance (CRcl) of ≥50 mL/min, b) Total bilirubin ≤1.5 X upper limit of normal and c) Aspartate aminotransferase (AST) or alkaline phosphatase ≤2.5 X ULN.

KEY EXCLUSION CRITERIA

Patients with:

  1. Allogenic bone marrow transplant/stem cell transplant
  2. Persistent, clinically significant, chronic toxicities from prior AML therapy that would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with study procedures
  3. Acute promyelocytic leukemia
  4. Disseminated intravascular coagulation
  5. Active infections, unless adequately treated with antibiotic, antiviral, or antifungal agents within in 7 days before Induction Day 1
  6. Active central nervous system involvement by AML
  7. Other active malignancies or other malignancies within the last 12 months except nonmelanoma skin cancer or cervical intraepithelial neoplasia
  8. A requirement for hemodialysis or peritoneal dialysis
  9. A history of myocardial infarction within the 3 months before treatment with vosaroxin
  10. A history of cerebrovascular accident/transient ischemic attack within the 3 months before treatment with vosaroxin
  11. A thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days before treatment with vosaroxin
  12. Investigational products taken within 28 days before treatment with vosaroxin, and non-investigational cancer therapies or radiation therapy within 14 days before treatment with vosaroxin, with the exception of hydroxyurea.
  13. A known intolerance to cytarabine or known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin)
  14. Prior exposure to vosaroxin

  15. Any other medical, psychological, or social condition that contraindicates their participation in the clinical study due to safety concerns or compliance with study procedures in the opinion of the Investigator,or Sunesis Medical Monitor

    In addition:

  16. Women who are pregnant or breastfeeding
  17. Women who are of childbearing potential or male patients who had partners of childbearing potential who were unwilling to use an approved, effective means of contraception according to the study site's standards

Sites / Locations

  • HealthOne Presbyterian/St. Luke's Medical Center
  • Rocky Mountain Cancer Centers
  • H. Lee Moffitt Cancer Center
  • Northwestern Medical Faculty Foundation
  • Northwestern Memorial Hospital
  • Indiana University Cancer Center
  • Johns Hopkins University - Sidney Kimmel Cancer Center
  • New York Presbyterian Hospital-Weill Cornell Medical College
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Voreloxin injection and cytarabine

Arm Description

Dose-escalation Phase Schedule A: Schedule B: Expansion Phase Schedule A: Schedule B:

Outcomes

Primary Outcome Measures

Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)
Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.

Secondary Outcome Measures

Remission Rates (CR+CRp)
Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator. CR is defined as >1000 Neutrophils (ul), >100,000 Platelets (uL) and <5 BM Blasts (%); CRp is defined as >1000 Neutrophils (ul), <=100,000 Platelets (uL) and <5 BM Blasts (%); CRi is defined as >1000 Neutrophils (ul), <100,000 Platelets (uL) and <5 BM Blasts (%); 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 (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.
Leukemia-free Survival (LFS)
Leukemia-free survival is censored at the last known alive date without report of relapse.
Overall Survival
Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.
All Cause Mortality
Mortality of those patients enrolled in the study and receiving intervention

Full Information

First Posted
October 8, 2007
Last Updated
December 11, 2017
Sponsor
Sunesis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT00541866
Brief Title
Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans
Official Title
Phase 1b/2, Open-Label, Multicenter, Dose-Escalating, Clinical Study of the Safety, Tolerability, and PK and PD Profiles of Voreloxin Injection in Combination With Cytarabine in Patients With Relapsed or Refractory AML
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
October 6, 2007 (Actual)
Primary Completion Date
February 15, 2012 (Actual)
Study Completion Date
February 15, 2012 (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 safety and tolerability of voreloxin (vosaroxin) injection in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.
Detailed Description
An open-label, Phase 1b/2 study using a dose-escalation design with expansion at the maximum tolerated dose (MTD) using 2 dosing schedules: During the Schedule A dose-escalation phase, patients with relapsed or refractory acute myeloid leukemia (AML) enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dosing regimen of vosaroxin of 10 mg/m2 on Days 1 and 4 of each cycle in combination with a 24-hour continuous intravenous (CIV) infusion of cytarabine 400 mg/m2/day × 5 days. If none of the 3 patients or 1 of 6 patients experience a dose-limiting toxicity (DLT) at the vosaroxin starting dose, dose-escalate vosaroxin. If 2 of 6 patients experienced a DLT at the vosaroxin starting dose, reduce the dose of cytarabine to reduced to 200 mg/m2 (only case in which the cytarabine could have been reduced). The vosaroxin dose escalated following a modified Fibonacci schema. For Schedule B dose-escalation phase, patients with relapsed or refractory AML enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dose regimen of vosaroxin of 70 mg/m2 on Days 1 and 4 in combination with cytarabine as a 2-hour infusion of 1 g/m2/day × 5 days. No reductions of cytarabine allowed in Schedule B. If none of the 3 patients or 1 of 6 patients experienced a DLT in the first cohort of Schedule B, escalate the dose of vosaroxin. If DLTs occurred in 2 of 6 patients during the starting dose, reduce the vosaroxin dose to 50 mg/m2. For both Schedules, the highest dose at which fewer than 2 of 6 patients experienced a DLT during induction became the MTD and the recommended future dose. Once the MTD of vosaroxin was determined for Schedule A, first relapse patients were enrolled in the expansion phase at that dose level to obtain additional safety and efficacy information. When the MTD of vosaroxin was determined for Schedule B, first relapse patients and patients with primary refractory disease were enrolled in the expansion phase at that dose level to characterize the safety and efficacy profile in this population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Leukemia, Acute Myeloid, Relapsed, Refractory, Cancer, AML, Cytarabine, SNS-595, Phase 1, Voreloxin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Voreloxin injection and cytarabine
Arm Type
Experimental
Arm Description
Dose-escalation Phase Schedule A: Schedule B: Expansion Phase Schedule A: Schedule B:
Intervention Type
Drug
Intervention Name(s)
Voreloxin injection and cytarabine
Other Intervention Name(s)
ARA-C, Cytosar-U
Intervention Description
Dose-escalation Phase Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Expansion Phase The MTD determined in the dose-escalation phase was used in the expansion phase. Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days) Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)
Primary Outcome Measure Information:
Title
Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)
Description
Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.
Time Frame
From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.
Secondary Outcome Measure Information:
Title
Remission Rates (CR+CRp)
Description
Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator. CR is defined as >1000 Neutrophils (ul), >100,000 Platelets (uL) and <5 BM Blasts (%); CRp is defined as >1000 Neutrophils (ul), <=100,000 Platelets (uL) and <5 BM Blasts (%); CRi is defined as >1000 Neutrophils (ul), <100,000 Platelets (uL) and <5 BM Blasts (%); 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 (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.
Time Frame
Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years
Title
Leukemia-free Survival (LFS)
Description
Leukemia-free survival is censored at the last known alive date without report of relapse.
Time Frame
From time of the start of CR or CRp to the earliest date of relapse, commencement of reinduction therapy, or death, assessed monthly up to 2 years after the end of study visit.
Title
Overall Survival
Description
Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.
Time Frame
Time between the date of first study treatment and the date of death due to any cause for upto 2 years after the end of study visit
Title
All Cause Mortality
Description
Mortality of those patients enrolled in the study and receiving intervention
Time Frame
30 and 60 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
KEY INCLUSION CRITERIA Relapsed or refractory AML subtypes defined by WHO, except acute promyelocytic leukemia. Relapsed/refractory disease may be de novo AML or secondary AML Treated with one to threee induction/reinduction AML regimens, prior induction or consolidation therapy with cytarabine allowed At least 10% blasts by BM biopsy or aspirate Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Clinical laboratory values of a) Serum creatinine ≤1.5 mg/dL and calculated or measured creatinine clearance (CRcl) of ≥50 mL/min, b) Total bilirubin ≤1.5 X upper limit of normal and c) Aspartate aminotransferase (AST) or alkaline phosphatase ≤2.5 X ULN. KEY EXCLUSION CRITERIA Patients with: Allogenic bone marrow transplant/stem cell transplant Persistent, clinically significant, chronic toxicities from prior AML therapy that would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with study procedures Acute promyelocytic leukemia Disseminated intravascular coagulation Active infections, unless adequately treated with antibiotic, antiviral, or antifungal agents within in 7 days before Induction Day 1 Active central nervous system involvement by AML Other active malignancies or other malignancies within the last 12 months except nonmelanoma skin cancer or cervical intraepithelial neoplasia A requirement for hemodialysis or peritoneal dialysis A history of myocardial infarction within the 3 months before treatment with vosaroxin A history of cerebrovascular accident/transient ischemic attack within the 3 months before treatment with vosaroxin A thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days before treatment with vosaroxin Investigational products taken within 28 days before treatment with vosaroxin, and non-investigational cancer therapies or radiation therapy within 14 days before treatment with vosaroxin, with the exception of hydroxyurea. A known intolerance to cytarabine or known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin) Prior exposure to vosaroxin Any other medical, psychological, or social condition that contraindicates their participation in the clinical study due to safety concerns or compliance with study procedures in the opinion of the Investigator,or Sunesis Medical Monitor In addition: Women who are pregnant or breastfeeding Women who are of childbearing potential or male patients who had partners of childbearing potential who were unwilling to use an approved, effective means of contraception according to the study site's standards
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sunesis Medical Monitor, MD
Organizational Affiliation
Sunesis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
HealthOne Presbyterian/St. Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern Medical Faculty Foundation
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46206
Country
United States
Facility Name
Johns Hopkins University - Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
New York Presbyterian Hospital-Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Aggregate data of Adverse Events
Citations:
PubMed Identifier
25381131
Citation
Lancet JE, Roboz GJ, Cripe LD, Michelson GC, Fox JA, Leavitt RD, Chen T, Hawtin R, Craig AR, Ravandi F, Maris MB, Stuart RK, Karp JE. A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia. Haematologica. 2015 Feb;100(2):231-7. doi: 10.3324/haematol.2014.114769. Epub 2014 Nov 7.
Results Reference
derived

Learn more about this trial

Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

We'll reach out to this number within 24 hrs