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

NCT00541866 | Completed Phase 1 Results

• 1 other identifier: SPO-0012
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 9

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.

Conditions

Acute Myeloid Leukemia

Keywords

Leukemia; Acute Myeloid; Relapsed; Refractory; Cancer; AML; Cytarabine; SNS-595; Phase 1; Voreloxin

Outcome Measures

Primary Outcomes (1)

• 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.

  From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.

Secondary Outcomes (4)

• Remission Rates (CR+CRp)

  Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years

• Leukemia-free Survival (LFS)

  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.

• Overall Survival

  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

• All Cause Mortality

  30 and 60 days

Study Arms (1)

Voreloxin injection and cytarabine

EXPERIMENTAL

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

Drug: Voreloxin injection and cytarabine

Interventions

Voreloxin injection and cytarabine DRUG

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)

Also known as: ARA-C, Cytosar-U

Voreloxin injection and cytarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunesis Pharmaceuticals: lead

Study Sites (9)

HealthOne Presbyterian/St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46206, United States

Location

Johns Hopkins University - Sidney Kimmel Cancer Center

Baltimore, Maryland, 21205, United States

Location

New York Presbyterian Hospital-Weill Cornell Medical College

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 25381131 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Recurrence; Neoplasms

Interventions

vosaroxin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Further study is needed to confirm the results due to limited sampling size. Statistical fields are not included here because no statistical testings were performed to compare any of the treatment groups. No p-values or odds ratios were reported.

Results Point of Contact

• Title: Mike Johnston, Senior Director Regulatory Affairs
• Organization: Sunesis Pharmaceuticals, Inc.

mjohnston@sunesis.com

(650) 266-3727

Study Officials

• Sunesis Medical Monitor, MD

  Sunesis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2007
• First Posted: October 10, 2007
• Study Start: October 6, 2007
• Primary Completion: February 15, 2012
• Study Completion: February 15, 2012
• Last Updated: January 9, 2018
• Results First Posted: January 9, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)