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

Phase 2

Completed

Conditions: Trisomy 8
MDS
Myelodysplastic Syndrome

Interventions: Drug: rigosertib

Registration Number: NCT01584531

Lead Sponsor: Traws Pharma, 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
21-Day Regimen	rigosertib	560 mg oral rigosertib in the morning and 280 mg rigosertib in the afternoon on days 1 to 21 of 21-day cycle

Primary Outcome Measures

Name	Time	Method
Number of units of red blood cell transfusions	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

Name	Time	Method
Number of Adverse Events (AEs)	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.
Bone marrow blasts	4 weeks	Change in number of bone marrow blasts will be compared to pretreatment.
Complete blood count	4 weeks	Complete blood count with differential.

Trial Locations

Locations (4): Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Winship Cancer Institute, Emory University
🇺🇸
Atlanta, Georgia, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Bon Secours St. Francis Hospital
🇺🇸
Greenville, South Carolina, United States