Randomized Study of ON 01910.Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts
ONTIME
Phase III MultiCenter Randomized Controlled Study to Assess Efficacy and Safety of ON 01910.Na 72-Hr Continuous IV Infusion in MDS Patients With Excess Blasts Relapsing After or Refractory to or Intolerant to Azacitidine or Decitabine
1 other identifier
interventional
299
6 countries
87
Brief Summary
The primary objective of this study is to compare overall survival (OS) in patients receiving ON 01910.Na + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome (MDS) with excess blasts (5% to 30% bone marrow blasts) who have failed azacitidine or decitabine treatment. This patient population has no available therapy and a short life expectancy (approximately 4 months). The high level of bone marrow activity of ON 01910.Na documented in Phase 1 and 2 studies has the potential to delay substantially the transition of MDS to Acute Myeloid Leukemia(AML), a very significant and severe complication, which shortens survival of these MDS patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2010
Longer than P75 for phase_3
87 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 1, 2010
CompletedStudy Start
First participant enrolled
November 1, 2010
CompletedFirst Posted
Study publicly available on registry
November 16, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 3, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2018
CompletedJune 30, 2020
July 1, 2018
7.9 years
November 1, 2010
June 29, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival
Overall survival (OS) is defined as the time from randomization to death from any cause. All patients will be followed until death or progression, even if they have discontinued treatment for whatever cause. Patients lost to follow-up will be censored at the time last known alive. The OS primary analysis will compare the active ON 01910.Na regimen to BSC once a total number of 223 deaths has been reached.
Up to 18 months
Secondary Outcomes (8)
Overall response (complete and partial remission) according to 2006 IWG criteria
Changes measured at Week 4 from Baseline and every 8 Weeks thereafter
Complete bone marrow response according to 2006 IWG criteria
Changes measured at Week 4 from Baseline and every 8 Weeks thereafter
Hematological improvements according to 2006 IWG criteria
Weekly
Scores of Quality of Life Questionnaire
Measured at Baseline and every 4 Weeks
Adverse events
Weekly
- +3 more secondary outcomes
Study Arms (2)
ON 01910.Na + best supportive care (BSC)
EXPERIMENTALPatients will receive ON 01910.Na 1800 mg/24 hr as a continuous intravenous infusion for 72 hours every other week for the first 16 weeks then every 4 weeks afterwards and best supportive care (BSC).
Best supportive care (BSC)
NO INTERVENTIONPatients will receive best supportive care (BSC).
Interventions
The dose of ON 01910.Na will be 1800 mg/24 hr as a continuous intravenous infusion for 72 hours every other week for the first 16 weeks then every 4 weeks afterwards. Infusion bags must be changed every 24 hours and a new infusion bag must be used for each of the subsequent 24 hours until completion of the total 72-hour infusion time.
Eligibility Criteria
You may qualify if:
- MDS diagnosis confirmed within 6 weeks prior to entry according to WHO or FAB classification
- MDS classified as follows, according to WHO and FAB classification:
- RAEB-1 (5% - 9% BM blasts)
- RAEB-2 (10% - 19% BM blasts)
- CMML (10% - 20% BM blasts) and WBC \< 13,000/μL
- RAEB-t (20% - 30% BM blasts), with following criteria:
- o WBC \< 25 x 10E9/L at entry
- o Stable WBC at least 4 weeks prior to entry and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukopheresis.
- At least one cytopenia (ANC \< 1800/µL or platelet count \< 100,000/µL or hemoglobin \<10 g/dL)
- Progression according to 2006 International Working Group (IWG) criteria any time after start of azacitidine or decitabine during past 2 years; or failure to achieve complete or partial response or hematological improvement (according to 2006 IWG) after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine during past 2 years; or relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria) observed after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine during past 2 years; or, intolerance to azacitidine or decitabine defined by drug-related ≥Grade 3 liver or renal toxicity leading to discontinuation during the past 2 years.
- Did not respond to, relapsed after, not eligible for, or opted not to do bone marrow transplantation
- Off other MDS treatments for at least 4 weeks; Filgrastim (G-CSF) and erythropoietin allowed before and during the study as clinically indicated.
- No need for induction chemotherapy
- ECOG status 0, 1 or 2
- Willing to adhere to protocol prohibitions and restrictions
- +1 more criteria
You may not qualify if:
- Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding) unless stabilized for 1 week after RBC transfusion.
- 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.
- Alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal (ULN)
- Serum creatinine ≥2.0 mg/dL
- Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<130 mEq/L)
- Pregnant or lactating females
- Patients unwilling to follow strict contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine device, double-barrier method \[spermicidal jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) before entry and throughout the study
- Females with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin pregnancy test at screening
- Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start
- Uncontrolled hypertension (defined as systolic pressure ≥160 mmHg and/or diastolic pressure ≥110 mmHg)
- New onset seizures (within 3 months prior to first dose of ON 01910.Na) or poorly controlled seizures
- Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Traws Pharma, Inc.lead
- The Leukemia and Lymphoma Societycollaborator
Study Sites (87)
Virginia G. Piper Cancer Center
Scottsdale, Arizona, 85258, United States
University of California San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Stanford Cancer Center
Stanford, California, 94305, United States
Yale Cancer Center
New Haven, Connecticut, 06520, United States
Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Integrated Community Oncology Network
Jacksonville, Florida, 32256, United States
Innovative Medical Research of South Florida, Inc.
Miami, Florida, 33169, United States
Mount Sinai Comprehensive Cancer Centers
Miami Beach, Florida, 33140, United States
Woodlands Medical Specialists
Pensacola, Florida, 32503, United States
Martin Memorial Cancer Center
Stuart, Florida, 34994, United States
Cleveland Clinic Florida
Weston, Florida, 33331, United States
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
North Shore Medical Center
Evanston, Illinois, 60201, United States
Cardinal Bernardin Cancer Center
Maywood, Illinois, 60153, United States
Edward H. Kaplan MD & Associates
Skokie, Illinois, 60076, United States
University of Kansas Medical Center
Westwood, Kansas, 66205, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21231, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Providence Cancer Center
Southfield, Michigan, 48075, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Overlook Hospital
Summit, New Jersey, 07901, United States
North Shore - LIJ Health System
Lake Success, New York, 11042, United States
Weill Cornell Medical College
New York, New York, 10021, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Albert Einstein College of Medicine
The Bronx, New York, 10461, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104, United States
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Bon Secours St. Francois Health System
Greenville, South Carolina, 29601, United States
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390, United States
University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030, United States
Cancer Care Centers of South Texas
San Antonio, Texas, 78229, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
H. Hartziekenhuis Roeselare-Menen vzw
Roeselare, West-vlaanderen, 8800, Belgium
Ziekenhuis Netwerk Antwerpen
Antwerp, 2060, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
CHU de Mont-Godinne
Yvoir, 5530, Belgium
CHU Angers Service de Medecine D - Maladies du Sang
Angers, 49033, France
CHU Avignon Centre Hospitalier Henri Dufaut
Avignon, 84000, France
Hôpital Avicenne Hématologie Clinique
Bobigny, 93009, France
CHU Caen Hématologie Clinique
Caen, 14000, France
CHU Estaing Service d'hématologie
Clermont-Ferrand, 63000, France
CHU Lille Hôpital Claude Huriez
Lille, 59037, France
CHU Limoges Hopital Dupuytren
Limoges, 87042, France
Institute Paoli Calmettes
Marseille, 13009, France
Hôpital de L'archet I
Nice, 6202, France
Hôtel Dieu Sce Hématologie Clinique
Paris, 75004, France
Hôpital Saint-Antoine
Paris, 75571, France
CHU Perpignan Centre Hospitalier Hôpital Saint-Jean
Perpignan, 66046, France
CRLCC Henri Becquerel
Rouen, 76038, France
Chu-Strasbourg-Hopital Civil
Strasbourg, 67091, France
Hôpital Purpan
Toulouse, 31059, France
Universitätsklinikum Bonn
Bonn, North Rhine-Westphalia, 53127, Germany
Universitätsklinikum zu Köln
Cologne, 50924, Germany
Universitätsklinikum Dresden
Dresden, 01307, Germany
Heinrich-Heine-Universität Düsseldorf
Düsseldorf, 40225, Germany
Klinikum der Johann Wolfgang-Goethe-Universität
Frankfurt am Main, 60590, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
Universitätsmedizin Mannheim
Mannheim, 68167, Germany
Johannes-Wesling-Klinikum Minden
Minden, 32429, Germany
Klinikum Rechts der Isar der Technischen Universität München
München, 81675, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
Siena, SI, 53100, Italy
Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo
Alessandria, 15100, Italy
Azienda Ospedaliero-Universitaria di Bologa Policlinico S. Orsola-Malpighi
Bologna, 40138, Italy
Azienda Ospedaliera-Universitairia Vittorio Emanuele-Ferrarotto-Santo Bambino
Catania, 95124, Italy
Azienda Ospedaliera Universitaria Careggi di Firenze
Florence, 50134, Italy
Azienda Ospedaliera Universitaria San Martino
Genova, 16132, Italy
Azienda Osperdaliera Universitaria Maggiore della Carità
Novara, 28100, Italy
Università degli Studi La Sapienza
Roma, 00161, Italy
Azienda Ospedaliero Universitaria San Giovanni Battista di Torino
Torino, 10126, Italy
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33006, Spain
Hospital Universitario La Princesa
Madrid, 28006, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Clínico Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario Son Espases
Palma de Mallorca, 07012, Spain
Hospital Clínico Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitari i Politècnic La Fe
Valencia, 46009, Spain
Hospital Clínico Universitario de Valencia
Valencia, 46010, Spain
Related Publications (6)
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.
PMID: 21924492BACKGROUNDAthuluri-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.
PMID: 27104980BACKGROUNDGarcia-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.
PMID: 26968357RESULTNavada 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.
PMID: 27400247RESULTAl-Kali A. Relationship of bone marrow blast (BMBL) response to overall survival (OS) in a multicenter study of rigosertib (Rigo) in patients (pts) with myelodysplastic syndrome (MDS) with excess blasts progressing on or after treatment with a hypomethylating agent (HMA). Journal of Clinical Oncology 2017 35:15_suppl, 7056-7056 ASCO 2017
RESULTGarcia-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.
RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Steven M. Fruchtman, MD
Traws Pharma, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 1, 2010
First Posted
November 16, 2010
Study Start
November 1, 2010
Primary Completion
October 3, 2018
Study Completion
October 3, 2018
Last Updated
June 30, 2020
Record last verified: 2018-07