Myelodysplastic SyndromePhase 1/2NCT01980056
Vosaroxin for Intermediate 2 or High-risk MDS After Failure With Hypomethylating Agent-based Therapy
A Phase 1/2 study testing Vosaroxin in people with Myelodysplastic Syndrome, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Vosaroxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2013to 19 Jan 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Primary failure/refractory: Stable or worsening disease after a minimum of 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy
- Secondary failure/relapse: Bone marrow blast count increase or loss of hematologic response after initial treatment response with hypomethylating agent-based therapy
- Intolerance: Intolerance of hypomethylating agent-based therapy regardless of number of cycles completed and clinical response
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- 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:
- Serum creatinine 1.5 ≤ x the upper limit of normal (ULN) or calculated creatinine clearance (CLCR) of ≥ 50 mL/min
- 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).
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN
- 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).
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College
New York, New York, 10065
About this study
Official title: 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.
Read the 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.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Vosaroxin
- Keywords
- INT-2 or high-risk MDS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VosaroxinDrug
Also called Qinprezo
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
| Study group | Role | What they receive |
|---|---|---|
| Vosaroxin: All Patients | Experimental | All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Receives: Drug: Vosaroxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dosage Determination for IV-infusion of Vosaroxin in Int-2 or High-risk Mds
Maximum tolerated dose of vosaroxin for short IV infusion in INT-2 or high-risk MDS
Measured: 1 year
Secondary outcomes (2)
Number of Subjects Who Experience a Response
Evaluate the clinical activity of vosaroxin in MDS subjects by observing number of patients who achieve complete remission.
Measured: 15 months
Number of Transfusions Required During Treatment With Vosaroxin
Characterize the blood product transfusion requirements in this patient population when treated with vosaroxin
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2013 (estimated)
- Study start25 Oct 2013
- Primary completion19 Jan 2015
- Study completion19 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- Dose level 1: Vosaroxin 50 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Sunesis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Gail Roboz, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980056
- Sponsor's protocol ID
- 1305013919
- Other IDs
- IST/VOS/MDS
- Status last verified
- Jan 2019
- First submitted
- 1 Nov 2013
- Last updated
- 19 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01980056
- Acronym / sponsor ID
- 1305013919
- Conditions
- Myelodysplastic Syndrome
- Keywords
- INT-2 or high-risk MDS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Sunesis Pharmaceuticals
- Study start
- 25 Oct 2013 (actual)
- Primary completion
- 19 Jan 2015 (actual)
- Study completion
- 19 Jan 2015 (actual)
- First posted
- 8 Nov 2013 (estimated)
- Results
- Posted 28 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose level 1: Vosaroxin 50 mg/m^2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg/m^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
| Arm | Type | Receives |
|---|---|---|
| Vosaroxin: All Patients | Experimental | Drug: VosaroxinAll patients will receive vosaroxin according to the dose cohort in which they are enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2
- Must have a life expectancy of at least 2 months
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VosaroxinAlso: QinprezoDose 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 | Drug | Vosaroxin: All Patients |
Primary outcome
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
2 secondary outcomes
Number of Subjects Who Experience a Response
Time frame: 15 months
Number of Transfusions Required During Treatment With Vosaroxin
Time frame: 15 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gail Roboz, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vosaroxin in people with Myelodysplastic Syndrome, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dosage Determination for IV-infusion of Vosaroxin in Int-2 or High-risk Mds (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2019.