Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome (ONTARGET)
Primary Purpose
Myelodysplastic Syndrome, MDS, Trisomy 8
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rigosertib
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring rigosertib sodium, rigosertib, ON 01910.Na, oral rigosertib
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic
- Winship Cancer Institute, Emory University
- Mayo Clinic
- Columbia University Medical Center
- Bon Secours St. Francis Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
21-Day Regimen
Arm Description
560 mg oral rigosertib in the morning and 280 mg rigosertib in the afternoon on days 1 to 21 of 21-day cycle
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Adverse Events (AEs)
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
Change in number of bone marrow blasts will be compared to pretreatment.
Complete blood count
Complete blood count with differential.
Full Information
NCT ID
NCT01584531
First Posted
April 23, 2012
Last Updated
June 22, 2017
Sponsor
Onconova Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01584531
Brief Title
Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome
Acronym
ONTARGET
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Onconova Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome, MDS, Trisomy 8
Keywords
rigosertib sodium, rigosertib, ON 01910.Na, oral rigosertib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
21-Day Regimen
Arm Type
Experimental
Arm Description
560 mg oral rigosertib in the morning and 280 mg rigosertib in the afternoon on days 1 to 21 of 21-day cycle
Intervention Type
Drug
Intervention Name(s)
rigosertib
Other Intervention Name(s)
rigosertib sodium, ON 01910.Na, oral rigosertib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of units of red blood cell transfusions
Description
Number of units of red blood cell transfusions will be compared with the pretreatment transfusion number in the previous 8 weeks.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Number of Adverse Events (AEs)
Description
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.
Time Frame
From date of randomization until 30 days after last dose of study drug
Title
Bone marrow blasts
Description
Change in number of bone marrow blasts will be compared to pretreatment.
Time Frame
4 weeks
Title
Complete blood count
Description
Complete blood count with differential.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven M. Fruchtman, MD
Organizational Affiliation
Onconova Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Bon Secours St. Francis Hospital
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29601
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27400247
Citation
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.
Results Reference
background
Citation
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.
Results Reference
result
Links:
URL
http://www.lls.org/
Description
The Leukemia & Lymphoma Society
URL
http://www.mds-foundation.org/
Description
The Myelodysplastic Syndromes Foundation
URL
http://www.onconova.com/
Description
Website of Onconova Therapeutics, Inc.
Learn more about this trial
Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome
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