Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA

Myelodysplastic Syndrome Clinical Trial

— INSPIRE  

Official title:

A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02562443
• Other study ID #: Onconova 04-30
• Secondary ID: 2015-001476-22
• Status: Terminated
• Phase: Phase 3
• Start date: December 2, 2015
• Est. completion date: July 26, 2021

Study information

• Verified date: September 2022
• Source: Onconova Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study's primary objective [in a population of patients with MDS after failure of treatment with azacitidine (AZA) or decitabine (DAC)], is to compare the overall survival (OS) of patients in the rigosertib group vs the Physician's Choice group, in all patients and in a subgroup of patients with IPSS-R very high risk.

Description:

This is a Phase III, open-label, randomized, controlled, international study. Approximately 360 patients < 82 years of age with MDS classified as RAEB-1, RAEB-2, or RAEB-t who received AZA or DAC for ≤ 9 months and/or ≤ 9 cycles over 12 months and had their last dose of AZA or DAC within 6 months prior to screening will be stratified by: - Very high risk (VHR) vs non-VHR per IPSS-R, and - Geographic region (North America vs Europe vs Asia; because approved products and standard of care may vary by region), and randomly assigned in a 2:1 ratio to one of the following 2 treatment groups: - Rigosertib 1800 mg/24 hr administered as a 72 hr CIV infusion on Days 1, 2, and 3 of a 2 week cycle for the first 8 cycles, and on Days 1, 2, and 3 of a 4-week cycle thereafter (N = approximately 240 patients); - Physician's Choice of alternative treatment, which may include any approved or standard-of-care therapy that the patient has not shown to be hypersensitive to, based on frequently used treatment for MDS, as per institutional guidelines, after receipt of HMAs (N = approximately 120 patients). The drugs used in the Physician's Choice arm should be used according to the recommendations, if clinically appropriate, provided in the corresponding Summary of Product Characteristics (SmPC) and Prescribing Information of these drugs. Experimental therapies are not allowed on the PC arm. Patients will be treated until 2006 IWG progression criteria are met (ie, 50% increase of BM blasts or worsening of cytopenias) or until an unacceptable toxicity or intolerance. For all randomized patients who discontinue study treatment, subsequent therapies with their start and end dates, as well as survival time after treatment discontinuation, will be documented at least monthly until death. Patients in the PC group who progress will not be allowed to cross over to rigosertib. All patients in both treatment groups will be allowed, as medically justified, access to RBC and platelet transfusions and to growth factors (granulocyte colony-stimulating factor (G-CSF), erythropoietin, and thrombopoietin).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 372
• Est. completion date: July 26, 2021
• Est. primary completion date: July 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 81 Years

Eligibility

Inclusion Criteria:

• MDS classified as follows:
• RAEB-1 per World Health Organization (WHO) MDS criteria (5% to <10% BM blasts)
• RAEB-2 per WHO MDS criteria (10% to <20% BM blasts)
• RAEB-t per French-American-British (FAB) classification (20% to 30% BM blasts)
• At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin [Hgb] < 10 g/dL)
• Progression (according to 2006 IWG criteria) at any time after initiation of AZA or DAC treatment or Failure to achieve complete or partial response or hematological improvement (HI) (according to 2006 IWG) after at least six 4-week cycles of AZA or either four 4-week or four 6-week cycles of DAC administered or Relapse after initial complete or partial response or HI (according to 2006 IWG criteria)
• Duration of prior HMA therapy = 9 months and/or total = 9 cycles of prior HMA therapy in = 12 months
• Last dose of AZA or DAC within 6 months before the planned date of randomization; however, must be off these treatments for = 4 weeks before randomization
• Has failed to respond to, relapsed following, not eligible for, or opted not to participate in allogeneic stem cell transplantation
• Off all treatments for MDS (including AZA and DAC) for = 4 weeks before randomization; growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Willing to adhere to protocol prohibitions and restrictions
• Patient must sign informed consent form to indicate patient's understanding study's purpose and procedures and willingness to participate. Should patient be incapable of giving consent, the patient's legally authorized representative (as defined by local regulation) must give consent. However, should patient, in any manner, choose not to participate this takes precedence and will be respected.
• Patients with 5q- syndrome should have failed to respond to or progressed on treatment with lenalidomide, where available and indicated

Exclusion Criteria:

• Previous participation in a clinical study of IV or oral rigosertib; patients who failed screening for other rigosertib studies may be screened for participation
• Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside plus 2-3 days of an anthracycline, or high-dose cytarabine
• Suitable candidate to receive allogeneic stem cell transplantation; patient is eligible for study if a suitable candidate refuses to undergo an allogeneic stem cell transplant or a suitable donor cannot be found
• Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ that is unlikely to progress in two years
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure or unstable angina pectoris
• Active infection not adequately responding to appropriate therapy
• Total bilirubin =1.5 mg/dL not related to hemolysis or Gilbert's disease
• Alanine transaminase (ALT)/aspartate transaminase (AST) =2.5 x upper limit of normal (ULN)
• Serum creatinine =2.0 mg/dL or eGFR (estimated Glomerular Filtration Rate) < 40 mL/min.
• Known active HIV, hepatitis B or hepatitis C, where active is defined as follows:
• HIV or hepatitis C - presence of viral load
• Hepatitis B - antigen positive
• Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)
• Female patients of child-bearing potential and male patients with sexual 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. Examples of acceptable contraception methods include:

• estrogen-gestagen based contraceptives associated with inhibition of ovulation (oral, intravaginal, transdermal),
• gestagen-only based contraceptives associated with inhibition of ovulation (oral, injectable, implantable),
• intra-uterine devices (IUDs),
• intra-uterine hormone-releasing systems (IUSs),
• bilateral tubal occlusion
• vasectomized partner
• sexual abstinence in accordance with an individual's lifestyle
• Female patients of child-bearing potential (pre-menopausal and not surgically sterilized) who are breast-feeding or have a positive blood beta-human chorionic gonadotropin pregnancy test at Screening
• Major surgery without full recovery or within 3 weeks before planned randomization;
• Uncontrolled hypertension
• New onset seizures (within 3 months before planned randomization) or poorly controlled seizures
• Any other concurrent investigational agent or chemotherapy, radiotherapy, immunotherapy, or corticosteroids (prednisone up to 20 mg/day or its equivalent is permitted for chronic conditions)
• Treatment with cytarabine at any dose, lenalidomide, or any other therapy targeted to the treatment of MDS (other than growth factors and other supportive care measures) within 4 weeks of planned randomization
• Investigational therapy within 4 weeks of planned randomization
• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.
• Patient previously diagnosed with AML (defined as a bone marrow or peripheral blood blast percentage of >30%).

Related Conditions & MeSH terms

• Anemia, Refractory, with Excess of Blasts
• MDS
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• RAEB
• Refractory Anemia With Excess Blasts
• Syndrome

Intervention

Drug:
• rigosertib
Patients will receive intravenous rigosertib 1800 mg/24 hr for 3 days every 2 weeks for first 8 cycles, then every 4 weeks thereafter + best supportive care (BSC).
• Any approved or standard-of-care therapy
Patients will receive Physician's Choice of Treatment or alternative treatment which may include any approved or standard-of-care therapy, based on frequently used treatment for MDS (no experimental therapy) + best supportive care.
• best supportive care (BSC)
Patients will receive best supportive care (BSC): azacitidine (AZA) and/or decitabine (DAC) are permitted.
• best supportive care (BSC)
Patients will receive best supportive care (BSC).

Locations

Country	Name	City	State
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Monash Health, Monash Medical Centre	Melbourne	Victoria
Australia	Icon Cancer Care Icon South Brisbane	South Brisbane	Queensland
Austria	Hospital of the Elisabethinen Linz GmbH	Linz
Austria	Salzburg University Hospital	Salzburg
Austria	Hanusch Hospital	Vienna
Belgium	Antwerp Hospital Network Stuivenberg	Antwerp
Belgium	University Hospital Ghent	Ghent
Belgium	University Hospital Leuven, Campus Gasthuisberg	Leuven
Belgium	CHU UCL Namur - Site Godinne	Yvoir
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Croatia	Klinicki bolnicki centar Osijek	Osijek
Croatia	Clinical Hospital Merkur	Zagreb
Croatia	Klinicki bolnicki centar Sestre milosrdnice	Zagreb
Croatia	Klinicki bolnicki centar Zagreb	Zagreb
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Hradec Kralove	Hradec Kralove
Czechia	University Hospital Ostrava, Department of Hematooncology	Ostrava Poruba
Czechia	General University Hospital	Prague 2
Czechia	Institute of Hematology and Blood Transfusion	Prague 2
Estonia	North Estonia Medical Centre	Tallinn
Estonia	Tartu University Hospital	Tartu
France	CHD Vendée	La Roche Sur Yon Cedex 9
France	Hôpital Claude Huriez, CHRU Lille	Lille Cedex
France	Institut Paoli-Calmettes	Marseille
France	Hôpital l'Archet 1	Nice Cedex 3
France	Institut de Cancérologie du Gard	Nimes Cedex 9
France	Hôpital Saint Louis	Paris Cedex 10
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	Hôpital civil, Strasbourg	Strasbourg Cedex
France	CHRU Tours Hôspital Bretonneau	Tours
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Marien Hospital Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Frankfurt am Main	Frankfurt
Hungary	Semmelweis University Medical School	Budapest
Hungary	Somogy County Kaposi Mór Teaching Hospital	Kaposvár
Hungary	Jósa András Teaching Hospital	Nyíregyháza
Hungary	University of Pécs 1st Department of Internal Medicine	Pécs
India	Hemato Oncology Clinic Pvt. Ltd	Ahmedabad	Gujarat
India	St. John's Medical College Hospital	Bangalore	Karnataka
India	Institute Of Hematology And Transfusion Medicine	Kolkata	West Bengal
India	Jaslok Hospital and Research Center	Mumbai	Maharashtra
India	Tata Memorial Hospital	Mumbai	Maharashtra
India	Sahyadri Clinical Research and Development Center	Pune	Maharashtra
India	Christian Medical College	Vellore	Tamil Nadu
Ireland	Cork University Hospital	Cork
Ireland	Adelaide and Meath Hospital, Incorporating the National Children's Hospital	Dublin
Ireland	University Hospital Waterford	Waterford
Israel	Ha'Emek Medical Center	'Afula
Israel	Soroka University Medical Center	Beer Sheva
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Kaplan Medical Center	Rehovot
Israel	Sourasky Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Italy	Polyclinic S. Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliera Spedali Civili	Brescia
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Azienda Ospedaliero-Universitaria Maggiore della Carità	Novara
Italy	A.O.U. Pisana, Divisione di Ematologia - University Hospital of Pisa	Pisa
Italy	Ospedale S. Eugenio - S. Eugenio Hospital	Roma
Italy	Policlinico Universitario Tor Vergata	Roma
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni
Italy	Cittá della Salute e della Scienza di Torino	Torino
Japan	Akita University Hospital	Akita
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyo-ku
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi
Japan	Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers	Fukuyama	Hiroshima
Japan	Shimane University Hospital	Izumo	Shimane
Japan	Kagoshima University Hospital	Kagoshima
Japan	Tokai Central Hospital of the Mutual Aid Association of Public School Teachers	Kakamigahara
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	Saitama Medical Center	Kawagoe
Japan	Kokura Memorial Hospital	Kitakyushu	Fukuoka
Japan	Kobe City Hospital Organization Kobe City Medical Center General Hospital	Kobe
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto
Japan	Japanese Red Cross Kyoto Daini Hospital	Kyoto
Japan	Nagasaki University Hospital	Nagasaki
Japan	Japanese Red Cross Nagoya Daini Hospital	Nagoya-shi
Japan	Niigata University Medical and Dental Hospital	Niigata
Japan	Oita Prefectural Hospital	Oita
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Kindai University Hospital	Osakasayama-shi
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Tohoku University Hospital	Sendai-shi
Japan	Japanese Red Cross Medical Center	Shibuya	Tokyo
Japan	NTT Medical Center Tokyo	Shinagawa-ku
Japan	Tokyo Medical University Hospital	Shinjuku-ku
Japan	Dokkyo Medical University Hospital	Tochigi
Japan	Tokushima University Hospital	Tokushima
Japan	Yamagata University Hospital	Yamagata
Japan	Saiseikai Yokohamashi Nanbu Hospital	Yokohama-shi
Japan	Yokohama City University Hospital	Yokohama-shi	Kanagawa
Japan	University of Fukui Hospital	Yoshida
Poland	Independent Public Healthcare Facility University Hospital in Cracow, Clinical Department of Hematology	Kraków
Poland	Independent Public Health Care Facility of the Ministry of Internal Affairs with Warmia and Mazury Oncology Centre in Olsztyn	Olsztyn
Poland	Ludwik Rydygier Provinicial Hospital in Suwalki, Department of Clinical Oncology and Hematology	Suwalki
Poland	MTZ Clinical Research Sp. z o.o.	Warsaw
Poland	Independent Public University Hospital No. 1 in Wroclaw, Department of Hematology, Blood Cancers and Bone Marrow	Wroclaw
Russian Federation	State Autonomous Healthcare Institution of Kemerovo region "Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev",	Kemerovo
Russian Federation	State Budgetary Healthcare Institution of Moscow City	Moscow
Russian Federation	FSBI "Russian Scientific Research Hematology and Tranfusiology Institute of the Federal Biomedical Agency"	Saint Petersburg
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Duran i Reynals - Instituto Catalán de Oncología	Hospitalet de Llobregat	Barcelona
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Son Llàtzer	Palma de Mallorca	Balearic Islands
Spain	Hospital Universitario Salamanca	Salamanca
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Sweden	Linköping University Hospital	Linköping	Östergötland
Sweden	Skåne University Hospital, Department of Hematology	Lund
Sweden	Karolinska University Hospital	Stockholm	Huddinge
Sweden	Uppsala University Hospital	Uppsala
Switzerland	University Hospital and University of Bern; Inselspital Bern	Bern
Switzerland	University Hospital Zurich	Zurich
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	The Royal Liverpool University Hospital	Liverpool
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	St Bartholomew's Hospital, Barts Health NHS Trust	London
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	Emily Couric Clinical Cancer Center	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Cancer Specialists of North Florida	Fleming Island	Florida
United States	UF Health Shands Cancer Hospital	Gainesville	Florida
United States	Greenville Health System (GHS) Cancer Institute	Greenville	South Carolina
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Health Hospital	Indianapolis	Indiana
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	UCLA Medical Center	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Loyola University Chicago at Loyola University Medical Center	Maywood	Illinois
United States	University of Minnesota Physicians Bone Marrow Transplant Clinic	Minneapolis	Minnesota
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Mid Florida Hematology and Oncology Centers	Orange City	Florida
United States	Albert Einstein Medical Center, Cancer Center	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Mayo Clinic	Rochester	Minnesota
United States	Advanced Research Institute, Inc	Saint Petersburg	Florida
United States	Seattle Cancer Care Alliance (SCCA)	Seattle	Washington
United States	New York Medical College	Valhalla	New York
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Onconova Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Croatia,  Czechia,  Estonia,  France,  Germany,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Poland,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (4)

Athuluri-Divakar SK, Vasquez-Del Carpio R, Dutta K, Baker SJ, Cosenza SC, Basu I, Gupta YK, Reddy MV, Ueno L, Hart JR, Vogt PK, Mulholland D, Guha C, Aggarwal AK, Reddy EP. A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling. Cell. 2016 Apr 21;165(3):643-55. doi: 10.1016/j.cell.2016.03.045. — View Citation

Garcia-Manero G, Fenaux P, Al-Kali A, Baer MR, Sekeres MA, Roboz GJ, Gaidano G, Scott BL, Greenberg P, Platzbecker U, Steensma DP, Kambhampati S, Kreuzer KA, Godley LA, Atallah E, Collins R Jr, Kantarjian H, Jabbour E, Wilhelm FE, Azarnia N, Silverman LR; ONTIME study investigators. Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial. Lancet Oncol. 2016 Apr;17(4):496-508. doi: 10.1016/S1470-2045(16)00009-7. Epub 2016 Mar 9. — View 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.

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory Objective: Bone Marrow Genomic Mutational Status	Bone marrow genomic mutational status.	At screening, every 8 week during study treatment, and at the end of study treatment
Other	Exploratory Objective: Transition to Acute Myelogenous Leukemia (AML)	Transformation time to AML (defined as a bone marrow or peripheral blood blast percentage >30%).	Through study completion, an average of 8 months
Other	Safety Objective: Number of Patients with AEs.	Treatment-emergent adverse events (TEAEs) will be graded according to NCI CTCAE version 4, grouped by MedDRA preferred term, and summarized by worst grade of severity per patient by treatment group.	Monthly, through study completion
Other	Safety Objective: Rigosertib population pharmacokinetics (PK).	Blood samples for population PK analysis will be taken in rigosertib patients	At Cycle 1 (Week 1) and Cycle 2 (Week 3), on Day 1 of the infusion, 1 hr after its start and on Day 2 of the infusion, 6 hr after its start
Primary	Overall survival of all randomized patients and overall survival of patients scored as IPSS-R very high risk.	The overall survival (OS) of all randomized patients (ITT population), and the overall survival of patients scored as IPSS-R very high risk.	Up to 30 Months
Secondary	Overall survival of patients with monosomy 7 chromosomal aberrations.	Evaluate OS of patients with monosomy 7 chromosomal aberrations in the rigosertib vs PC group. Overall survival is the time (months) from date of randomization to date of death or date last known to be alive at the time of date cut-off.	Up to 30 Months
Secondary	Overall survival of patients with trisomy 8 chromosomal aberrations.	Evaluate OS of patients with trisomy 8 chromosomal aberrations in the rigosertib vs PC group. Overall survival is the time (months) from date of randomization to date of death or date last known to be alive at the time of date cut-off.	Up to 30 Months
Secondary	Percent of patients with response according to 2006 IWG criteria.	Responses of complete remission (CR), partial remission (PR), mCR, SD, failure, and PD will be determined by 2006 IWG criteria. The number and percent of patients with CR, PR, mCR, SD, Failure, or PD will be summarized by treatment group.	Up to 30 Months
Secondary	Scores of Quality of Life Questionnaire.	Compare rigosertib vs PC in regard to the the scores of the EuroQol EQ-5D-5L Questionnaire. The EuroQol EQ-5D-5L Questionnaire includes five levels of severity in each of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a visual analogue scale.	At Baseline, at Week 4, Every 4 Weeks thereafter, and at the End-of-treatment.
Secondary	Percent of patients with bone marrow blast response rate according to 2006 IWG criteria.	Compare rigosertib vs PC in regard to the bone marrow blast responses of marrow complete response (mCR = 50% decrease of BMBL vs pretreatment values to a value = 5%), marrow partial response (mPR, = 50% decrease of BMBL vs pretreatment values to a value > 5%), stable disease (SD, no mCR or mPR, but no progressive disease (PD), and PD (= 50% BMBL increase relative to baseline or nadir) will be assessed. The number and percent of patients with mCR, mPR, SD, or PD will be summarized by treatment group. Responses of complete remission (CR), partial remission (PR), mCR, SD, failure, and PD will be determined by 2006 International Working Group (IWG) criteria.	Up to 30 Months
Secondary	Percent of patients with hematologic improvement (HI) (erythroid, platelet and neutrophil responses) according to 2006 IWG criteria.	Compare rigosertib vs PC in regard to the number and percent of patients who meet the 2006 IWG criteria.	Up to 30 Months