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
18 Years
N/A
Both
Myelodysplastic Syndrome, MDS, Trisomy 8
Trial Information
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
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 on an outpatient basis 560 mg rigosertib BID for 14 consecutive days of a 21-day
cycle. (Note: Protocol was amended to delete the arm in which administration of rigosertib
was a continuous regimen on days 1 to 21 of 21-day cycle because higher incidence of urinary
symptoms was observed in this arm.)
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 and then will only be allowed in patients with
hemoglobin levels of less than 9 g/dL. Rigosertib dosing adjustment policies are described
in Protocol.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of units of red blood cell transfusions
Outcome Description:
Number of units of red blood cell transfusions will be compared with the pretreatment transfusion number in the previous 8 weeks.
Outcome Time Frame:
8 weeks
Safety Issue:
No
Principal Investigator
François E. Wilhelm, MD, PhD
Investigator Role:
Study Director
Investigator Affiliation:
Onconova Therapeutics, Inc.
Authority:
United States: Food and Drug Administration
Study ID:
Onconova 09-05
NCT ID:
NCT01584531
Start Date:
May 2012
Completion Date:
October 2014
Related Keywords:
- Myelodysplastic Syndrome
- MDS
- Trisomy 8
- rigosertib sodium
- rigosertib
- ON 01910.Na
- oral rigosertib
- Myelodysplastic Syndromes
- Preleukemia
- Trisomy
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
| Mayo Clinic | Scottsdale, Arizona |
| Columbia University Medical Center | New York, New York 10032 |
| Bon Secours St. Francis Hospital | Greenville, South Carolina 29601 |
