Myelodysplastic SyndromePhase 1NCT02075034
Three Dosing Schedules of Oral Rigosertib in MDS Patients
A Phase 1 study testing rigosertib in people with Myelodysplastic Syndrome, run by Traws Pharma, Inc. at 1 site in United States.
Trial summary
This study will compare the dosing regimen of oral rigosertib, which has been used in other studies of lower risk Myelodysplastic Syndrome (MDS), with 2 new dosing regimens to determine if one of the new regimens gives improved results as measured by disease status, side effects, and analyses of blood and urine… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- rigosertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Nov 2019
- Phase
- Phase 1
- 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 or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening.
- MDS classified as Low-risk or Int-1 risk or Int-2 risk according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as High-risk since their MDS was diagnosed.
- Transfusion dependency defined by transfusion of at least 4 units of RBC (red blood cells) within 8 weeks before Screening; pre-transfusion Hgb (hemoglobin) values must be ≤ 9 g/dL to be taken into account.
- Refractory to 8- to 12-week course of ESA (erythropoiesis stimulating agent) 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 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 the protocol.
- The patient must signed an informed consent form (ICF).
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 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.
- Active infection not adequately responding to appropriate therapy.
Show all 20Show fewer
- 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 of child-bearing potential or male patients with partners of child-bearing potential who are unwilling to follow strict contraception requirements before entry and throughout the study, up to and including the 30-day non-treatment follow-up period.
- Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening or who are lactating.
- 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 chemotherapy, radiotherapy, or immunotherapy.
- Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hour equivalent prednisone) within 4 weeks of Baseline/Cycle 1 Day 1 visit.
- Investigational therapy within 4 weeks of Screening.
- Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: A Randomized Phase I Study to Assess the Pharmacokinetics, Tolerability, Efficacy and Pharmacodynamics of Three Dosing Schedules of Oral Rigosertib in Transfusion-dependent, Low, Intermediate 1, or Intermediate-2 Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System
This study will compare the dosing regimen of oral rigosertib, which has been used in other studies of lower risk Myelodysplastic Syndrome (MDS), with 2 new dosing regimens to determine if one of the new regimens gives improved results as measured by disease status, side effects, and analyses of blood and urine samples.
Read the detailed description
This will be a Phase I, randomized, 3-treatment arm, single-center study in transfusion-dependent Myelodysplastic Syndrome (MDS) patients classified as Low- or Intermediate-1 (Int-1) or Intermediate-2 (Int-2) risk by the International Prognostic Scoring System (IPSS). Initially, 18 patients (6 per treatment arm) will be randomized in a 1:1:1 ratio to 1 of 3 oral rigosertib dosing regimens, each of which is a cycle consisting of 14 consecutive days of dosing followed by 7 days off drug.
Treatment with erythropoiesis-stimulating agent (ESA) is prohibited for the first 15 weeks (5 cycles). After 15 weeks of dosing (5 cycles), ESA treatment will be initiated if the patient still needs red blood cell (RBC) transfusions and if the pre-transfusion hemoglobin (Hgb) value is ≤ 9 g/dL, unless the clinical judgment of the Investigator determines ESA administration to a patient with a Hgb level > 9 g/dL is warranted.
All study participants will be allowed, as medically justified, access to RBC and platelet (PLT) transfusions, and to filgrastim. Rigosertib dosing adjustment policies are described.
After all 18 patients have completed 3 cycles, a risk/benefit analysis will be completed assessing the distribution of adverse events (AEs) and serious adverse events (SAEs) and the number of transfusions among the 3 treatment arms. This analysis will select 1 of the 3 dosing regimens as having the best risk/benefit profile and an additional 12 to 18 patients will be enrolled at this dosing regimen. Eligibility criteria may be modified by protocol amendments to enroll patients with different characteristics. All patients will be treated for 48 weeks or until 2006 International Working Group (IWG) progression criteria are met, unacceptable toxicity is observed, intercurrent illness or a change in the patient's condition prevents further administration of study drug treatment, or until death from any cause occurs, whichever comes first. Patients who have continued hematologic response at 48 weeks may continue to be treated in the study beyond 48 weeks until 2006 IWG progression criteria are met or until death from any cause, whichever comes first.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- rigosertib
- Keywords
- Myelodysplastic syndrome, MDS, Low risk, Intermediate-1 risk, Intermediate-2 risk, International Prognostic Scoring System, IPSS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rigosertibDrug
Also called ON 01910.Na
Rigosertib will be supplied as soft gel capsules in strengths of 280 mg and 70 mg.
| Study group | Role | What they receive |
|---|---|---|
| 560 mg morning/280 mg afternoon | Experimental | Two 280 mg capsules of rigosertib will be taken in the morning and one 280 mg capsule of rigosertib will be taken in the afternoon. Receives: Drug: rigosertib |
| 420 mg morning and afternon | Experimental | One 280 mg capsule and two 70 mg capsules of rigosertib will be taken in the morning and one 280 mg capsule and two 70 mg capsules of rigosertib will be taken in the afternoon. Receives: Drug: rigosertib |
| 280 mg TID | Experimental | One 280 mg capsule of rigosertib will be taken in the morning, one 280 mg capsule of rigosertib will be taken at mid-day, and one 280 mg capsule of rigosertib will be taken in the afternoon. Receives: Drug: rigosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Micrograms of rigosertib per milliliter of plasma
Concentration of rigosertib in plasma will be determined by validated high performance liquid chromatography (HPLC) method.
Measured: 0, 0.5, 1, 1.5, 2, 4, 6, and 8 hour on Day 1 of Cycle 1 and on Day 1 of Cycle 2.
Micrograms of rigosertib per milliliter of urine
Concentration of rigosertib in urine will be determined by a validated high performance liquid chromatography (HPLC) method.
Measured: Cycle 1 Day 1 and Cycle 2 Day 1 in dosing Regimens 1 and 2 and Cycle 1 Day 1 and Cycle 2 Day 21 in dose Regimen 3
Number of patients with adverse events
Adverse events will be summarized by worst grade according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
All AE presentations will summarize treatment-emergent adverse events (TEAEs), defined as AEs with onset on or after first dose, or onset prior to first dose but with worsening severity after first dose.
Measured: Until 30 days after last dose of study drug (up to 52 weeks)
Secondary outcomes (2)
Proportion of patients with hematologic improvement (HI)
HI is defined according to IWG criteria (Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006; 108:419-25.) and include Erythroid response, Neutrophil response and Platelet response.
Measured: 24 weeks
Concentration of biomarkers in urine
Biomarkers will be measured by immunoassay.
Measured: Up to Cycle 2 Day 15 (up to day 36)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2014 (estimated)
- Study startMay 2014
- Primary completionAug 2019 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Traws Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Heaney, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02075034
- Sponsor's protocol ID
- Onconova 09-10
- Status last verified
- Jul 2018
- First submitted
- 27 Feb 2014
- Last updated
- 1 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase I Study to Assess the Pharmacokinetics, Tolerability, Efficacy and Pharmacodynamics of Three Dosing Schedules of Oral Rigosertib in Transfusion-dependent, Low, Intermediate 1, or Intermediate-2 Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System
- ClinicalTrials.gov ID
- NCT02075034
- Acronym / sponsor ID
- Onconova 09-10
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Myelodysplastic syndrome, MDS, Low risk, Intermediate-1 risk, Intermediate-2 risk, International Prognostic Scoring System, IPSS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Traws Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2014
- Primary completion
- Aug 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 3 Mar 2014 (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.
This study will compare the dosing regimen of oral rigosertib, which has been used in other studies of lower risk Myelodysplastic Syndrome (MDS), with 2 new dosing regimens to determine if one of the new regimens gives improved results as measured by disease status, side effects, and analyses of blood and urine samples.
Detailed description
This will be a Phase I, randomized, 3-treatment arm, single-center study in transfusion-dependent Myelodysplastic Syndrome (MDS) patients classified as Low- or Intermediate-1 (Int-1) or Intermediate-2 (Int-2) risk by the International Prognostic Scoring System (IPSS). Initially, 18 patients (6 per treatment arm) will be randomized in a 1:1:1 ratio to 1 of 3 oral rigosertib dosing regimens, each of which is a cycle consisting of 14 consecutive days of dosing followed by 7 days off drug.
Treatment with erythropoiesis-stimulating agent (ESA) is prohibited for the first 15 weeks (5 cycles). After 15 weeks of dosing (5 cycles), ESA treatment will be initiated if the patient still needs red blood cell (RBC) transfusions and if the pre-transfusion hemoglobin (Hgb) value is ≤ 9 g/dL, unless the clinical judgment of the Investigator determines ESA administration to a patient with a Hgb level > 9 g/dL is warranted.
All study participants will be allowed, as medically justified, access to RBC and platelet (PLT) transfusions, and to filgrastim. Rigosertib dosing adjustment policies are described.
After all 18 patients have completed 3 cycles, a risk/benefit analysis will be completed assessing the distribution of adverse events (AEs) and serious adverse events (SAEs) and the number of transfusions among the 3 treatment arms. This analysis will select 1 of the 3 dosing regimens as having the best risk/benefit profile and an additional 12 to 18 patients will be enrolled at this dosing regimen. Eligibility criteria may be modified by protocol amendments to enroll patients with different characteristics. All patients will be treated for 48 weeks or until 2006 International Working Group (IWG) progression criteria are met, unacceptable toxicity is observed, intercurrent illness or a change in the patient's condition prevents further administration of study drug treatment, or until death from any cause occurs, whichever comes first. Patients who have continued hematologic response at 48 weeks may continue to be treated in the study beyond 48 weeks until 2006 IWG progression criteria are met or until death from any cause, whichever comes first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 560 mg morning/280 mg afternoon | Experimental | Drug: rigosertibTwo 280 mg capsules of rigosertib will be taken in the morning and one 280 mg capsule of rigosertib will be taken in the afternoon. |
| 420 mg morning and afternon | Experimental | Drug: rigosertibOne 280 mg capsule and two 70 mg capsules of rigosertib will be taken in the morning and one 280 mg capsule and two 70 mg capsules of rigosertib will be taken in the afternoon. |
| 280 mg TID | Experimental | Drug: rigosertibOne 280 mg capsule of rigosertib will be taken in the morning, one 280 mg capsule of rigosertib will be taken at mid-day, and one 280 mg capsule of rigosertib will be taken in the afternoon. |
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 or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening.
- MDS classified as Low-risk or Int-1 risk or Int-2 risk according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as High-risk since their MDS was diagnosed.
- Transfusion dependency defined by transfusion of at least 4 units of RBC (red blood cells) within 8 weeks before Screening; pre-transfusion Hgb (hemoglobin) values must be ≤ 9 g/dL to be taken into account.
- Refractory to 8- to 12-week course of ESA (erythropoiesis stimulating agent) 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 for at least 2 weeks prior to Screening.
Key exclusion criteria (20 listed)
- Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal 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.
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 |
|---|---|---|
| rigosertibAlso: ON 01910.NaRigosertib will be supplied as soft gel capsules in strengths of 280 mg and 70 mg. | Drug | 280 mg TID, 420 mg morning and afternon, 560 mg morning/280 mg afternoon |
Primary outcome
Micrograms of rigosertib per milliliter of plasma
Time frame: 0, 0.5, 1, 1.5, 2, 4, 6, and 8 hour on Day 1 of Cycle 1 and on Day 1 of Cycle 2.
Concentration of rigosertib in plasma will be determined by validated high performance liquid chromatography (HPLC) method.
Micrograms of rigosertib per milliliter of urine
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 in dosing Regimens 1 and 2 and Cycle 1 Day 1 and Cycle 2 Day 21 in dose Regimen 3
Concentration of rigosertib in urine will be determined by a validated high performance liquid chromatography (HPLC) method.
Number of patients with adverse events
Time frame: Until 30 days after last dose of study drug (up to 52 weeks)
Adverse events will be summarized by worst grade according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. All AE presentations will summarize treatment-emergent adverse events (TEAEs), defined as AEs with onset on or after first dose, or onset prior to first dose but with worsening severity after first dose.
2 secondary outcomes
Proportion of patients with hematologic improvement (HI)
Time frame: 24 weeks
Concentration of biomarkers in urine
Time frame: Up to Cycle 2 Day 15 (up to day 36)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
- 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.
Mark Heaney, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rigosertib in people with Myelodysplastic Syndrome, run by Traws Pharma, Inc. at 1 site in United States.
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 20 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: withdrawn, as of the sponsor's last update on 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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?
Micrograms of rigosertib per milliliter of plasma (time frame: 0, 0.5, 1, 1.5, 2, 4, 6, and 8 hour on Day 1 of Cycle 1 and on Day 1 of Cycle 2.). The study lists 3 primary outcomes in all. 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 NCT02075034, which also lists 1 linked publication.
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 1 Jul 2020.