Trial record 1 of 1 for:    NCT01913951
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Vosaroxin and Azacitidine in Treating Patients With Myelodysplastic Syndromes

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01913951
First received: July 30, 2013
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This phase I trial studies the side effects and the best dose of vosaroxin when given together with azacitidine in treating patients with myelodysplastic syndromes. Drugs used in chemotherapy, such as vosaroxin and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: vosaroxin
Drug: Azacitidine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Vosaroxin Plus Azacitidine for Patients With Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • MTD of vosaroxin in combination with azacitidine [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Defined as the highest dose of vosaroxin that results in a DLT in =< 1 of 6 patients graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0


Secondary Outcome Measures:
  • Best response (including hematologic improvement) [ Time Frame: At 3 cycles ] [ Designated as safety issue: No ]
    According to the modified IWG criteria. Summarized as proportion with 95% confidence intervals.

  • Best overall response [ Time Frame: Up to 7 months ] [ Designated as safety issue: No ]
    According to the modified IWG criteria. Summarized as proportion with 95% confidence intervals

  • Incidence of adverse events [ Time Frame: Up to 7 months ] [ Designated as safety issue: Yes ]
    Graded according to NCI CTCAE v. 4.0. summarized by grade, type and patient.

  • Time to response [ Time Frame: Up to 7 months ] [ Designated as safety issue: No ]
    According to the modified IWG criteria. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval.

  • Event-free survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    From the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval.

  • Progression-free survival (PFS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    From the date of first dose of study drug to disease progression or death from MDS. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval.

  • Disease-free survival (DFS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    From the date of first documentation of a complete remission (CR) to date of relapse. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval.

  • Overall survival (OS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    Date of first dose of study drug to the date of death from any cause. Described using Kaplan-Meier models to plot these endpoints and estimate median times with a 95% confidence interval.

  • Biomarkers of response to vosaroxin and azacitidine therapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Serial estimate of biomarker expression will be plotted and summarized over time using means and standard deviations, possibly on a log scale


Estimated Enrollment: 48
Study Start Date: November 2013
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vosaroxin, azacitidine)
Patients receive vosaroxin IV over 10 minutes on days 1 and 4 and azacitidine SC or IV over 15 minutes on days 1-7. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Drug: vosaroxin
Given IV over 10 minutes on Day 1 and 4
Other Name: voreloxin
Drug: Azacitidine
Given SC or IV over 15 minutes on days 1-7
Other Names:
  • Vidaza
  • Ladakamycin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of myelodysplastic syndrome and one of the following:

    • Cytopenias requiring red blood cell and/or platelet transfusions or neutropenia (ANC <1 X109/L)
    • IPSS score of INT-1 or higher at screening
    • MDS with excess blasts in transformation as defined by FAB criteria (20-29% bone marrow blasts) or
    • Chronic myelomonocytic leukemia
  • Age ≥18 years old
  • Adequate renal and hepatic function defined as all of the following:

    • total bilirubin ≤ 2.0 mg/dl, except in cases of Gilbert's disease;
    • AST and ALT ≤2.5 institutional ULN;
    • serum creatinine within normal institutional limits or estimated creatinine clearance ≥60 mL/min/1.73 m2 by the Cockcroft-Gault equation
  • ECOG performance status ≤2
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
  • Females must be surgically or biologically sterile or postmenopausal or if of childbearing potential, must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Patients may have received up to 3 prior cycles of hypomethylator therapy (i.e. decitabine or azacitidine) prior to enrollment and may have received supportive care measures (growth factors, erythropoietin stimulating agents, transfusion, etc.
  • Enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases").

Exclusion Criteria:

  • Prior treatment with four or more cycles of hypomethylator therapy.
  • Receiving concomitant chemotherapy, radiation therapy, or immunotherapy during the duration of treatment on protocol.
  • Known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and/or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01913951

Contacts
Contact: Meagan Jacoby, M.D., Ph.D. 314-362-9405 mjacoby@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Meagan Jacoby, M.D., Ph.D.    314-362-9405    mjacoby@dom.wustl.edu   
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Meagan Jacoby, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01913951     History of Changes
Other Study ID Numbers: 201309091
Study First Received: July 30, 2013
Last Updated: June 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014