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

NCT01980056 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1305013919IST/VOS/MDS
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Myelodysplastic Syndrome

Keywords

INT-2 or high-risk MDS

Outcome Measures

Primary Outcomes (1)

• 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

  1 year

Secondary Outcomes (2)

• Number of Subjects Who Experience a Response

  15 months

• Number of Transfusions Required During Treatment With Vosaroxin

  15 months

Study Arms (1)

Vosaroxin: All Patients

EXPERIMENTAL

All patients will receive vosaroxin according to the dose cohort in which they are enrolled.

Drug: Vosaroxin

Interventions

Vosaroxin DRUG

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

Also known as: Qinprezo

Vosaroxin: All Patients

Eligibility Criteria

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

You may qualify if:

• 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
• 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)
• % by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Sunesis Pharmaceuticals: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

vosaroxin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Weill Cornell Medicine

ray2013@med.cornell.edu

212-746-0284

Study Officials

• Gail Roboz, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 1, 2013
• First Posted: November 8, 2013
• Study Start: October 25, 2013
• Primary Completion: January 19, 2015
• Study Completion: January 19, 2015
• Last Updated: February 19, 2019
• Results First Posted: December 28, 2018

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)