Myelodysplastic SyndromesPhase 2NCT01904682
Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs
A Phase 2 study testing Oral rigosertib in people with Myelodysplastic Syndromes, run by Traws Pharma, Inc. at 14 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Oral rigosertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 14 sitesin 3 countries
- Study dates
- Jul 2013to May 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
United States10 sites
Anschutz Cancer Pavilion University of Colorado
Aurora, Colorado, 80045
Greenbaum Cancer Center University of Maryland
Baltimore, Maryland, 21201
The University of Chicago
Chicago, Illinois, 60637
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Mount Sinai Medical Center
New York, New York, 10029
Mayo Clinic
Rochester, Minnesota, 55905
Stanford University School of Medicine
Stanford, California, 94305
Washington Cancer Institute at Medstar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Germany3 sites
Universitätsklinikum Köln
Cologne, North Rhine-Westphalia, 50937
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Saxony, 01307
Heinrich Heine Universität
Düsseldorf, North Rhine-Westphalia, 40225
About this study
Official title: A Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Intermediate-1, Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System
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.
Read the 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
- Being tested
- Oral rigosertib
- Keywords
- Erythrocyte transfusion, Erythropoiesis-stimulating agent, International Prognostic Scoring System
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral rigosertibDrug
Also called ON 01910.Na, rigosertib sodium
Dose of 560 mg consists of two (2) 280 mg soft gel capsules of rigosertib.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Oral rigosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 Weeks
Secondary outcomes (3)
Overall Response
The number of patients with a complete remission or a partial remission will be documented. Complete remission and partial remission are defined according to 2006 IWG response criteria for MDS. Overall response = complete remission + partial remission.
Measured: Up to 2 years
Duration of Response
The number of weeks a complete remission or a partial remission is observed in a patient will be documented.
Measured: Up to 2 years
Number of Adverse Events
Specific safety parameters and procedures will include recording of medical history, medication history, physical examination, measurement of vital signs (blood pressure, temperature, respiration rate, and pulse), weight, laboratory evaluations, and toxicity and AE assessments.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2020
- Study completionMay 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steven M. Fruchtman, MD, Study chair, Traws Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01904682
- Sponsor's protocol ID
- Onconova 09-07
- Other IDs
- 2013-000672-15
- Status last verified
- Jun 2021
- First submitted
- 14 Jul 2013
- Last updated
- 16 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 21924492Navada 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.
PubMed 27400247Garcia-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.
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Intermediate-1, Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System
- ClinicalTrials.gov ID
- NCT01904682
- Acronym / sponsor ID
- Onconova 09-07
- Conditions
- Myelodysplastic Syndromes
- Keywords
- Erythrocyte transfusion, Erythropoiesis-stimulating agent, International Prognostic Scoring System
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2013
- Primary completion
- Dec 2020 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 22 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral rigosertib | Experimental | Drug: Oral rigosertibPatients 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral rigosertibAlso: ON 01910.Na, rigosertib sodiumDose of 560 mg consists of two (2) 280 mg soft gel capsules of rigosertib. | Drug | Oral rigosertib |
Primary outcome
Hematologic Improvement
Time frame: 24 Weeks
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.
3 secondary outcomes
Overall Response
Time frame: Up to 2 years
Duration of Response
Time frame: Up to 2 years
Number of Adverse Events
Time frame: Up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2021.
- Background: PubMed 21924492Seetharam 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.
- Background: PubMed 27400247Navada 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 publicationGarcia-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven M. Fruchtman, MD study chair
Traws Pharma, Inc.
14 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral rigosertib in people with Myelodysplastic Syndromes, run by Traws Pharma, Inc. at 14 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Germany, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hematologic Improvement (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01904682, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2021.