Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome (ONTARGET)

June 22, 2017 updated by: Onconova Therapeutics, Inc.

A Phase II, Multicenter, Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent Low or Intermediate-1 (Any Cytogenetics) or Trisomy 8 Intermediate-2 Myelodysplastic Syndrome Patients Based on IPSS Classification

The primary objectives of this study are to determine if rigosertib sodium, given orally in the form of soft gel capsules, is safe and is associated with a reduction in the number of blood transfusion units that are needed in patients with myelodysplastic syndrome (MDS) classified as Low or Intermediate-1 (Int-1) (any cytogenetics) or trisomy 8 Intermediate 2 (Int-2) in the International Prognostic Scoring System (IPSS) who are transfusion-dependent. Rigosertib will be taken on days 1 to 21 of a 21-day cycle.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This will be a Phase II open-label, multicenter (up to 5 centers), single-arm study. Sixty transfusion-dependent patients with MDS classified as Low or Int-1 risk (any cytogenetics) or trisomy 8 Int-2 by International Prognostic Scoring System (IPSS) will be enrolled to receive rigosertib BID for 21 consecutive days of a 21-day cycle.

Patients will be stratified on prior treatment with azacitidine and/or decitabine and/or lenalidomide and/or erythropoietin.

Patients will remain treated on study until 2006 Internation Working Group (IWG) progression criteria are met or until death from any cause.

All study participants will be allowed, as medically justified, access to RBC and platelet transfusions, and to filgrastim [G-CSF]. Erythropoiesis-stimulating agents (ESAs) will not be allowed during the initial 3 cycles. Rigosertib dosing adjustment policies are described in Protocol.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 2

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
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • South Carolina
      • Greenville, South Carolina, United States, 29601
        • Bon Secours St. Francis Hospital

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

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of MDS confirmed by bone marrow aspirate and/or biopsy within 6 weeks prior to first dose of study drug according to World Health Organization (WHO) or French-American-British (FAB) classification
  • MDS classified as Low risk or Int-1 risk (any cytogenetics) or Trisomy 8 Int-2 risk, according to IPSS classification
  • Transfusion dependency defined by at least 4 units of RBC administered within 8 weeks before baseline
  • Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, chemotherapy, immunosuppressive agents) for at least 4 weeks
  • ECOG performance status of 0, 1 or 2

Exclusion Criteria:

  • Ongoing clinically significant anemia due to factors such as iron, B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding, unless stabilized for 1 week after RBC transfusion
  • Serum ferritin <50 ng/mL
  • Hypoplastic MDS (cellularity <10%)
  • Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Active infection not adequately responding to appropriate therapy
  • Total bilirubin ≥1.5 mg/dL not related to hemolysis or Gilbert's disease
  • ALT/AST ≥2.5 x upper limit of normal (ULN)
  • Serum creatinine ≥2.0 mg/dL
  • Ascites requiring active medical management including paracentesis
  • Hyponatremia (defined as serum sodium value of <130 mEq/L)
  • Female patients who are pregnant or lactating
  • Patients who are unwilling to follow strict contraception requirements
  • Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (bHCG) pregnancy test at Screening
  • Major surgery without full recovery or major surgery within 3 weeks of rigosertib treatment start
  • Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic pressure ≥110 mmHg)
  • New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures
  • Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy
  • Chronic use (>2 weeks) of corticosteroids (>10 mg/24 hr equivalent prednisone) within 4 weeks of starting rigosertib
  • Investigational therapy within 4 weeks of starting rigosertib
  • Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements

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
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 21-Day Regimen
560 mg oral rigosertib in the morning and 280 mg rigosertib in the afternoon on days 1 to 21 of 21-day cycle
Drug: rigosertib

Rigosertib sodium will be available as soft gel capsules in strengths of 280 mg and 70 mg. Rigosertib will be administered on an outpatient basis.

Patients will take a 560 mg dose (e.g., 2 x 280 mg capsules) of oral rigosertib in the morning and 280 mg dose (e.g., 1 x 280 mg capsules) of oral rigosertib every day of 21-day cycles. Rigosertib should be taken in a fasting state (defined by at least 30 minutes before next meal) BID at 12 hr intervals (with a window of 2 hr). Any vomited dose will be reported as a missed dose.

The patient will fill a diary indicating the day and time of drug intake.

Other Names:
  • rigosertib sodium
  • ON 01910.Na
  • oral rigosertib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of units of red blood cell transfusions
Time Frame: 8 weeks
Number of units of red blood cell transfusions will be compared with the pretreatment transfusion number in the previous 8 weeks.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Adverse Events (AEs)
Time Frame: From date of randomization until 30 days after last dose of study drug
AEs reported by the patient or observed by the Investigator or study site personnel Safety assessments will be counted and documented on Case Report Forms and source documents. All AEs from signature of the ICF through 30 days after a patient discontinues from the study will be included.
From date of randomization until 30 days after last dose of study drug
Bone marrow blasts
Time Frame: 4 weeks
Change in number of bone marrow blasts will be compared to pretreatment.
4 weeks
Complete blood count
Time Frame: 4 weeks
Complete blood count with differential.
4 weeks

Collaborators and Investigators

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

Sponsor

Onconova Therapeutics, Inc.

Investigators

  • Study Director: Steven M. Fruchtman, MD, Onconova Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

May 1, 2012

Primary Completion (ACTUAL)

May 1, 2015

Study Completion (ACTUAL)

November 1, 2015

Study Registration Dates

First Submitted

April 23, 2012

First Submitted That Met QC Criteria

April 23, 2012

First Posted (ESTIMATE)

April 25, 2012

Study Record Updates

Last Update Posted (ACTUAL)

June 26, 2017

Last Update Submitted That Met QC Criteria

June 22, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Onconova 09-05
  • AAAJ0151 (OTHER: Columbia University)

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.

Clinical Trials on Myelodysplastic Syndrome

Clinical Trials on rigosertib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Liberia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe