Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA
NCT ID: NCT02562443
Last Updated: 2022-09-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE3
372 participants
INTERVENTIONAL
2015-12-02
2021-07-26
Brief Summary
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Detailed Description
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* 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).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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rigosertib + best supportive care (BSC)
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).
best supportive care (BSC)
Patients will receive best supportive care (BSC).
Physician's Choice (PC) + 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.
Interventions
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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).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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%).
18 Years
81 Years
ALL
No
Sponsors
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Traws Pharma, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Steven M. Fruchtman, MD
Role: STUDY_CHAIR
Traws Pharma, Inc.
Locations
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UC San Diego Moores Cancer Center
La Jolla, California, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
UCLA Medical Center
Los Angeles, California, United States
Cancer Specialists of North Florida
Fleming Island, Florida, United States
UF Health Shands Cancer Hospital
Gainesville, Florida, United States
Mid Florida Hematology and Oncology Centers
Orange City, Florida, United States
Advanced Research Institute, Inc
St. Petersburg, Florida, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Illinois Cancer Center
Chicago, Illinois, United States
Loyola University Chicago at Loyola University Medical Center
Maywood, Illinois, United States
Indiana University Health Hospital
Indianapolis, Indiana, United States
The University of Kansas Cancer Center
Westwood, Kansas, United States
Tulane Medical Center
New Orleans, Louisiana, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
University of Minnesota Physicians Bone Marrow Transplant Clinic
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
The Valley Hospital
Ridgewood, New Jersey, United States
Mount Sinai School of Medicine
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
New York Medical College
Valhalla, New York, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Albert Einstein Medical Center, Cancer Center
Philadelphia, Pennsylvania, United States
Greenville Health System (GHS) Cancer Institute
Greenville, South Carolina, United States
UT Southwestern Medical Center
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Emily Couric Clinical Cancer Center
Charlottesville, Virginia, United States
Seattle Cancer Care Alliance (SCCA)
Seattle, Washington, United States
University of Wisconsin Clinical Science Center
Madison, Wisconsin, United States
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States
Icon Cancer Care Icon South Brisbane
South Brisbane, Queensland, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Monash Health, Monash Medical Centre
Melbourne, Victoria, Australia
Hospital of the Elisabethinen Linz GmbH
Linz, , Austria
Salzburg University Hospital
Salzburg, , Austria
Hanusch Hospital
Vienna, , Austria
Antwerp Hospital Network Stuivenberg
Antwerp, , Belgium
University Hospital Ghent
Ghent, , Belgium
University Hospital Leuven, Campus Gasthuisberg
Leuven, , Belgium
CHU UCL Namur - Site Godinne
Yvoir, , Belgium
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Sunnybrook Research Institute
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
Klinički bolnički centar Osijek
Osijek, , Croatia
Clinical Hospital Merkur
Zagreb, , Croatia
Klinički bolnicki centar Sestre milosrdnice
Zagreb, , Croatia
Klinički bolnički centar Zagreb
Zagreb, , Croatia
University Hospital Brno
Brno, , Czechia
University Hospital Hradec Kralove
Hradec Králové, , Czechia
University Hospital Ostrava, Department of Hematooncology
Ostrava Poruba, , Czechia
General University Hospital
Prague, , Czechia
Institute of Hematology and Blood Transfusion
Prague, , Czechia
North Estonia Medical Centre
Tallinn, , Estonia
Tartu University Hospital
Tartu, , Estonia
CHD Vendée
La Roche-sur-Yon, , France
Hôpital Claude Huriez, CHRU Lille
Lille, , France
Institut Paoli-Calmettes
Marseille, , France
Hôpital l'Archet 1
Nice, , France
Institut de Cancérologie du Gard
Nîmes, , France
Hôpital Saint Louis
Paris, , France
Centre Hospitalier Lyon-Sud
Pierre-Bénite, , France
Hôpital civil, Strasbourg
Strasbourg, , France
CHRU Tours Hôspital Bretonneau
Tours, , France
Universitätsklinikum Carl Gustav Carus
Dresden, , Germany
Marien Hospital Düsseldorf
Düsseldorf, , Germany
Universitätsklinikum Frankfurt am Main
Frankfurt, , Germany
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, , Hungary
Hemato Oncology Clinic Pvt. Ltd
Ahmedabad, Gujarat, India
St. John's Medical College Hospital
Bangalore, Karnataka, India
Tata Memorial Hospital
Mumbai, Maharashtra, India
Jaslok Hospital and Research Center
Mumbai, Maharashtra, India
Sahyadri Clinical Research and Development Center
Pune, Maharashtra, India
Christian Medical College
Vellore, Tamil Nadu, India
Institute Of Hematology And Transfusion Medicine
Kolkata, West Bengal, India
Cork University Hospital
Cork, , Ireland
Adelaide and Meath Hospital, Incorporating the National Children's Hospital
Dublin, , Ireland
University Hospital Waterford
Waterford, , Ireland
Ha'Emek Medical Center
Afula, , Israel
Soroka University Medical Center
Beersheba, , 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 Litwinsky, , Israel
Polyclinic S. Orsola-Malpighi
Bologna, , Italy
Azienda Ospedaliera Spedali Civili
Brescia, , Italy
Azienda Ospedaliero Universitaria Careggi
Florence, , Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità
Novara, , Italy
A.O.U. Pisana, Divisione di Ematologia - University Hospital of Pisa
Pisa, , Italy
Policlinico Universitario Tor Vergata
Roma, , Italy
Ospedale S. Eugenio - S. Eugenio Hospital
Roma, , Italy
Azienda Ospedaliera Santa Maria di Terni
Terni, , Italy
Cittá della Salute e della Scienza di Torino
Torino, , Italy
Kokura Memorial Hospital
Kitakyushu, Fukuoka, Japan
Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers
Fukuyama, Hiroshima, Japan
Sapporo Medical University Hospital
Sapporo, Hokkaido, Japan
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, Japan
Yokohama City University Hospital
Yokohama, Kanagawa, Japan
Shimane University Hospital
Izumo, Shimane, Japan
Japanese Red Cross Medical Center
Shibuya City, Tokyo, Japan
Akita University Hospital
Akita, , Japan
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Bunkyō City, , Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, , Japan
Kagoshima University Hospital
Kagoshima, , Japan
Tokai Central Hospital of the Mutual Aid Association of Public School Teachers
Kakamigahara, , Japan
Saitama Medical Center
Kawagoe, , 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, , Japan
Niigata University Medical and Dental Hospital
Niigata, , Japan
National Hospital Organization Okayama Medical Center
Okayama, , Japan
Kindai University Hospital
Osakasayama-shi, , Japan
Oita Prefectural Hospital
Ōita, , Japan
Hokkaido University Hospital
Sapporo, , Japan
Tohoku University Hospital
Sendai, , 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, , Japan
University of Fukui Hospital
Yoshida, , Japan
Independent Public Healthcare Facility University Hospital in Cracow, Clinical Department of Hematology
Krakow, , 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
Suwałki, , 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, , Poland
State Autonomous Healthcare Institution of Kemerovo region "Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev",
Kemerovo, , Russia
State Budgetary Healthcare Institution of Moscow City
Moscow, , Russia
FSBI "Russian Scientific Research Hematology and Tranfusiology Institute of the Federal Biomedical Agency"
Saint Petersburg, , Russia
Hospital Son Llàtzer
Palma de Mallorca, Balearic Islands, Spain
Hospital Duran i Reynals - Instituto Catalán de Oncología
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitario Vall d'Hebron
Barcelona, , Spain
Hospital Universitari Germans Trias i Pujol
Barcelona, , Spain
Hospital Universitario Gregorio Marañón
Madrid, , Spain
Fundación Jiménez Díaz
Madrid, , Spain
Hospital Universitario Virgen de la Victoria
Málaga, , Spain
Hospital Universitario Salamanca
Salamanca, , Spain
Hospital Universitari i Politècnic La Fe
Valencia, , Spain
Karolinska University Hospital
Stockholm, Huddinge, Sweden
Skåne University Hospital, Department of Hematology
Lund, , Sweden
Uppsala University Hospital
Uppsala, , Sweden
Linköping University Hospital
Linköping, Östergötland County, Sweden
University Hospital and University of Bern; Inselspital Bern
Bern, , Switzerland
University Hospital Zurich
Zurich, , Switzerland
Royal Bournemouth Hospital
Bournemouth, Dorset, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom
The Royal Liverpool University Hospital
Liverpool, , United Kingdom
St Bartholomew's Hospital, Barts Health NHS Trust
London, , United Kingdom
King's College Hospital NHS Foundation Trust
London, , United Kingdom
Countries
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References
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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.
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.
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.
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.
Other Identifiers
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2015-001476-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
Onconova 04-30
Identifier Type: -
Identifier Source: org_study_id
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