Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs

NCT ID: NCT01904682

Last Updated: 2021-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2021-05-31

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.

Detailed Description

This will be a Phase II, single-arm, multicenter study (approximately 15 centers). Approximately 40 transfusion-dependent patients with Low- or Int-1 risk Myelodysplastic Syndrome (MDS) by International Prognostic Scoring System (IPSS) will be enrolled and treated with oral rigosertib administered twice daily for 21 consecutive days of a 21-day cycle (continuous regimen) in order to obtain at least 35 evaluable patients treated for at least 8 weeks. Patients will take 560 mg rigosertib (two 280 mg capsules) in the morning and 280 mg (one 280 mg capsule) in the afternoon, in fasting conditions. All patients on intermittent regimen at the time of Amendment 2 of the Protocol will be switched to the continuous regimen, including patients on reduced doses.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral rigosertib

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).

Group Type: EXPERIMENTAL

Oral rigosertib

Intervention Type: DRUG

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

Interventions

Oral rigosertib

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

Intervention Type: DRUG

Other Intervention Names

ON 01910.Na; rigosertib sodium

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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 Screening.
• Investigational therapy within 4 weeks of Screening.
• Allergy to a local anaesthetic.
• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Traws Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven M. Fruchtman, MD

Role: STUDY_CHAIR

Traws Pharma, Inc.

Locations

Stanford University School of Medicine

Stanford, California, United States

Anschutz Cancer Pavilion University of Colorado

Aurora, Colorado, United States

Washington Cancer Institute at Medstar Washington Hospital Center

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

The University of Chicago

Chicago, Illinois, United States

Greenbaum Cancer Center University of Maryland

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Mount Sinai Medical Center

New York, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Hôpital Saint-Louis, Service d'Hématologie

Paris, IDF, France

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, Germany

Heinrich Heine Universität

Düsseldorf, North Rhine-Westphalia, Germany

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, Saxony, Germany

Countries

United States; France; Germany

References

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.

Reference Type: BACKGROUND

PMID: 21924492 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27400247 (View on PubMed)

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.

Reference Type: RESULT

Other Identifiers

2013-000672-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Onconova 09-07

Identifier Type: -

Identifier Source: org_study_id