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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01584531
Recruitment Status : Completed
First Posted : April 25, 2012
Last Update Posted : June 26, 2017
Information provided by (Responsible Party):
Onconova Therapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome MDS Trisomy 8 Drug: rigosertib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2012
Actual Primary Completion Date : May 2015
Actual Study Completion Date : November 2015

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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. Bone marrow blasts [ Time Frame: 4 weeks ]
    Change in number of bone marrow blasts will be compared to pretreatment.

  3. Complete blood count [ Time Frame: 4 weeks ]
    Complete blood count with differential.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01584531

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United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, South Carolina
Bon Secours St. Francis Hospital
Greenville, South Carolina, United States, 29601
Sponsors and Collaborators
Onconova Therapeutics, Inc.
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Study Director: Steven M. Fruchtman, MD Onconova Therapeutics, Inc.

Additional Information:
Publications of Results:
Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.

Other Publications:
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Responsible Party: Onconova Therapeutics, Inc. Identifier: NCT01584531     History of Changes
Other Study ID Numbers: Onconova 09-05
AAAJ0151 ( Other Identifier: Columbia University )
First Posted: April 25, 2012    Key Record Dates
Last Update Posted: June 26, 2017
Last Verified: June 2017
Keywords provided by Onconova Therapeutics, Inc.:
rigosertib sodium
ON 01910.Na
oral rigosertib
Additional relevant MeSH terms:
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ON 01910
Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Chromosome Aberrations
Chromosome Duplication
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs