Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs

NCT01904682 | Completed Phase 2

• 2 other identifiers: Onconova 09-072013-000672-15
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 14

Brief Summary

The study will enroll low risk MDS patients who need red blood cell transfusions and who are refractory to or are not using erythropoiesis-stimulating agents. The purpose of the study is to determine whether oral rigosertib treatment results in hematological improvements according to the 2006 International Working Group criteria in these patients. The study will also record any side effects that may occur during the study.

Conditions

Myelodysplastic Syndromes

Keywords

Erythrocyte transfusion; Erythropoiesis-stimulating agent; International Prognostic Scoring System

Outcome Measures

Primary Outcomes (1)

• Hematologic Improvement

  The number of patients who achieve hematologic improvement will be documented. Hematologic improvement is defined by the 2006 International Working Group (IWG) response criteria for the erythroid, platelet and neutrophil lineages.

  24 Weeks

Secondary Outcomes (3)

• Overall Response

  Up to 2 years

• Duration of Response

  Up to 2 years

• Number of Adverse Events

  Up to 2 years

Study Arms (1)

Oral rigosertib

EXPERIMENTAL

Patients will take 560 mg oral rigosertib (two 280 mg capsules) in the morning and 280 mg (one 280 mg capsule) in the afternoon, in fasting conditions, for 21 consecutive days of 21-day cycle (continuous regimen).

Drug: Oral rigosertib

Interventions

Oral rigosertib DRUG

Dose of 560 mg consists of two (2) 280 mg soft gel capsules of rigosertib.

Also known as: ON 01910.Na, rigosertib sodium

Oral rigosertib

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 according to World Health Organization (WHO) criteria (Appendix 2) or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening.
• Myelodysplastic syndrome (MDS) classified as Low risk or Int-1 risk, according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as Int-2 or High-risk since their MDS was diagnosed;
• Transfusion dependency defined by transfusion of at least 4 units of Red blood cells (RBC) within 56 days before Screening (pre-transfusion Hgb values values must be ≤ 9 g/dL to be taken into account).
• Refractory to 8- to 12-week course of Erythropoiesis-stimulating agent (ESA) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ˃ 500 mU/mL and off ESA for at least 8 weeks before Screening.
• Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, chemotherapy, immunotherapy) for at least 2 weeks prior to Screening.
• Eastern Cooperative Oncology Group(ECOG) performance status of 0, 1 or 2.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• The patient must signed an informed consent form (ICF) indicating that s/he understands the purpose of, and procedures required for, the study and is willing to participate.

You may not qualify if:

• Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding.
• 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 ≥ 2.0 mg/dL not related to hemolysis or Gilbert's disease.
• Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x the 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 of childbearing potential who are unwilling to follow strict contraception requirements.
• Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening.
• Major surgery without full recovery or major surgery within 3 weeks of Screening.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (14)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Anschutz Cancer Pavilion University of Colorado

Aurora, Colorado, 80045, United States

Location

Washington Cancer Institute at Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Greenbaum Cancer Center University of Maryland

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hôpital Saint-Louis, Service d'Hématologie

Paris, IDF, 75475, France

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Heinrich Heine Universität

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, Saxony, 01307, Germany

Location

Related Publications (3)

• Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW, Sridhar K, Wilhelm F, Greenberg PL. Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leuk Res. 2012 Jan;36(1):98-103. doi: 10.1016/j.leukres.2011.08.022. Epub 2011 Sep 14.

  PMID: 21924492 BACKGROUND

• 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

MeSH Terms

Conditions

Myelodysplastic Syndromes

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 CHAIR

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: July 14, 2013
• First Posted: July 22, 2013
• Study Start: July 1, 2013
• Primary Completion: December 1, 2020
• Study Completion: May 1, 2021
• Last Updated: June 16, 2021

Record last verified: 2021-06

Locations

DE (3); US (10); FR (1)