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

NCT01584531 | Completed Phase 2

• 2 other identifiers: Onconova 09-05AAAJ0151
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 5

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.

Conditions

Myelodysplastic Syndrome; MDS; Trisomy 8

Keywords

rigosertib sodium; rigosertib; ON 01910.Na; oral rigosertib

Outcome Measures

Primary Outcomes (1)

• Number of units of red blood cell transfusions

  Number of units of red blood cell transfusions will be compared with the pretreatment transfusion number in the previous 8 weeks.

  8 weeks

Secondary Outcomes (3)

• Number of Adverse Events (AEs)

  From date of randomization until 30 days after last dose of study drug

• Bone marrow blasts

  4 weeks

• Complete blood count

  4 weeks

Study Arms (1)

21-Day Regimen

EXPERIMENTAL

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

Interventions

rigosertib DRUG

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.

Also known as: rigosertib sodium, ON 01910.Na, oral rigosertib

21-Day Regimen

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (5)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Bon Secours St. Francis Hospital

Greenville, South Carolina, 29601, United States

Location

Related Publications (2)

• Navada SC, Silverman LR. The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. Expert Rev Anticancer Ther. 2016 Aug;16(8):805-10. doi: 10.1080/14737140.2016.1209413. Epub 2016 Jul 15.

  PMID: 27400247 BACKGROUND

• 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.

  RESULT

Related Links

• The Leukemia \& Lymphoma Society
• The Myelodysplastic Syndromes Foundation

MeSH Terms

Conditions

Myelodysplastic Syndromes; Chromosome 8, trisomy

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Steven M. Fruchtman, MD

  Traws Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 25, 2012
• Study Start: May 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: November 1, 2015
• Last Updated: June 26, 2017

Record last verified: 2017-06

Locations

US (5)