Vosaroxin for Intermediate 2 or High-risk MDS After Failure With Hypomethylating Agent-based Therapy

January 24, 2019 updated by: Weill Medical College of Cornell University

A Phase 1/2, Open-label, Dose Escalation Clinical Study of the Safety and Clinical Activity of Vosaroxin in Patients With Intermediate 2 or High-risk Myelodysplastic Syndrome (MDS) After Failure of Hypomethylating Agent-based Therapy

Study WCMC IST/VOS/MDS evaluates the safety and tolerability of escalating doses of vosaroxin in adult patients with pathologically confirmed Myelodysplastic Syndrome, or MDS, (< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification with an intermediate 2 (INT-2) or high-risk score (ie, ≥ 1.5) as assessed by the International Scoring System (IPSS) after failure of hypomethylating agent-based therapy. Based on 3 completed studies and xenograft models, Vosaroxin is hypothesized to be safe and will effective in this patient population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase 1-2, dose escalation study of the safety and clinical activity of vosaroxin in subjects with INT-2 or high risk MDS who have failed prior hypomethylating agent based therapy. The study will utilize a standard 3+3 design to estimate the MTD [maximum tolerated dose] for vosaroxin administered to subjects with MDS. MTD will be defined as the highest dose level at which no more than 33% of the subjects observed at a given dose level experience a DLT [dose limiting toxicity]. Subjects will be assessed for safety and DLT in the first cycle of vosaroxin. Subjects will be enrolled into the study in cohorts of 3. Three eligible subjects will be enrolled in sequential cohorts at increasing dose levels until at least 1 DLT is observed during the first cycle of vosaroxin therapy. Subjects who receive both doses of vosaroxin will be evaluated for the MTD, DLTs, and safety profile during the first cycle of therapy. Once the MTD has been determined, an expanded evaluation of safety and hematologic response or improvement rate at this dose level will be conducted in additional subjects so that the total number of subjects exposed to this dose level is up to 15 subjects, inclusive of those treated at this dose level in the dose-escalation phase. The exposure of additional subjects at the MTD will provide a better estimate of the toxicity rate. Subjects with a documented response of Complete Response, Partial Response, or hematologic improvement at the end of Cycle 2 may continue to receive vosaroxin for additional cycles at the discretion of the treating investigator and after discussion with the medical staff at Sunesis Pharmaceuticals. There will be a 30-day follow-up period following the termination of study drug treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Able to understand and to provide written informed consent
  • At least 18 years of age with pathologically confirmed MDS (< 20% blasts in bone marrow, peripheral blood, or both) by WHO classification with an intermediate 2 or high-risk score assessed by IPSS (score ≥ 1.5)

  • Must have received at least 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy and are either refractory to, relapsed after, or are intolerant of prior therapy with either agent.

    1. Primary failure/refractory: Stable or worsening disease after a minimum of 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy
    2. Secondary failure/relapse: Bone marrow blast count increase or loss of hematologic response after initial treatment response with hypomethylating agent-based therapy
    3. Intolerance: Intolerance of hypomethylating agent-based therapy regardless of number of cycles completed and clinical response
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2
  • Must have a life expectancy of at least 2 months

  • Must demonstrate adequate clinical laboratory values (based on local laboratory results) as follows:

    1. Serum creatinine 1.5 ≤ x the upper limit of normal (ULN) or calculated creatinine clearance (CLCR) of ≥ 50 mL/min
    2. Total bilirubin ≤ 1.5 x ULN, higher levels are acceptable if these can be attributed to active hemolysis (as indicated by positive Coomb's test, decreased haptoglobin, Gilbert's disease, elevated indirect bilirubin, and/or lactate dehydrogenase) or ineffective erythropoiesis (as indicated by bone marrow findings).
    3. Aspartate aminotransferase (AST) ≤ 2.5 x ULN
    4. Alanine aminotransferase (ALT) ≤ 2.5 x ULN
    5. Must show adequate cardiac function defined as a left ventricular ejection fraction (LVEF)
  • 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
  • Must have acceptable recovery from clinically significant non-hematologic toxicity after prior therapy
  • Must be infertile or agree to use an effective contraceptive method for the duration of the study and for 30 days after the last dose (for men and women of child-producing potential).

Exclusion Criteria:

  • Patients meeting any of the following criteria are excluded:
  • Presence of AML (≥ 20% blasts in bone marrow, peripheral blood, or both)
  • Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
  • Have known active central nervous system disease or active, uncontrolled, clinically significant infection(s).
  • Have other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before enrollment, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
  • Have experienced CTCAE Grade 2 or greater oral mucositis within the last 14 days
  • Are receiving any other investigational therapy or protocol-prohibited therapy
  • Have received previous treatment with vosaroxin
  • Pregnant or breastfeeding females
  • Known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin)
  • Treatment with any anticancer therapy (including radiation) within the previous 14 days prior to the first dose of study drug or less than full recovery (CTCAE grade 1) from the clinically significant toxic effects of that treatment.
  • Treatment with any investigational drugs within the previous 14 days prior to Cycle 1, Day 1 or ongoing adverse events from previous cancer treatment with investigational drugs, regardless of the time period.
  • Have any other medical, psychological, or social condition that, in the opinion of the PI, would contraindicate the patient's participation in the clinical study due to safety or compliance with clinical study procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vosaroxin: All Patients
All patients will receive vosaroxin according to the dose cohort in which they are enrolled.
Drug: Vosaroxin
Dose level 1: Vosaroxin 50 mg^m2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg^m2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg^m2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Other Names:
  • Qinprezo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dosage Determination for IV-infusion of Vosaroxin in Int-2 or High-risk Mds
Time Frame: 1 year
Maximum tolerated dose of vosaroxin for short IV infusion in INT-2 or high-risk MDS
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Subjects Who Experience a Response
Time Frame: 15 months
Evaluate the clinical activity of vosaroxin in MDS subjects by observing number of patients who achieve complete remission.
15 months
Number of Transfusions Required During Treatment With Vosaroxin
Time Frame: 15 months
Characterize the blood product transfusion requirements in this patient population when treated with vosaroxin
15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Weill Medical College of Cornell University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sunesis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gail Roboz, MD, Weill Medical College of Cornell University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 25, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 19, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 19, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 1, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 8, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 19, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1305013919
  • IST/VOS/MDS (Other Identifier: Weill Cornell Medical College)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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