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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01913951
First received: July 30, 2013
Last updated: February 18, 2017
Last verified: February 2017
  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: Intervention Model: Single Group Assignment
Masking: No masking
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 ]
    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 ]
    According to the modified IWG criteria. Summarized as proportion with 95% confidence intervals.

  • Best overall response [ Time Frame: Up to 7 months ]
    According to the modified IWG criteria. Summarized as proportion with 95% confidence intervals

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

  • Time to response [ Time Frame: Up to 7 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Serial estimate of biomarker expression will be plotted and summarized over time using means and standard deviations, possibly on a log scale


Enrollment: 35
Actual Study Start Date: November 22, 2013
Estimated Study Completion Date: December 31, 2021
Primary Completion Date: December 5, 2016 (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   (Adult, Senior)
Sexes Eligible for Study:   All
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.
  • Either enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases"), which facilitates collection of blood, bone marrow, and skin for correlative studies, or consents to collection of blood, bone marrow, and skin as part of this protocol.

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. Patients who are seropositive for HCV, but have a negative viral load are also eligible. Documentation that the patients have completed a course of therapy for HCV is required and will be obtained.
  • 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

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
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: February 18, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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

ClinicalTrials.gov processed this record on March 24, 2017