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Myelodysplastic SyndromesPhase 3ONTIMENCT01241500

Randomized Study of ON 01910.Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts

A Phase 3 study testing ON 01910.Na in people with Myelodysplastic Syndromes and MDS, run by Traws Pharma, Inc. at 87 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes, MDS, RAEB
What is being tested?
ON 01910.Na
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
299 participants
Where
87 sitesin 6 countries
Study dates
Nov 2010to 3 Oct 2018
Phase
Phase 3
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

  • 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:
Show all 16Show fewer
  • 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
  • Patient (or a legally authorized representative) must sign informed consent form to indicate patient's understanding study's purpose and procedures and willingness to participate

Who cannot join

  • 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)
Show all 17Show fewer
  • 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
  • Prior treatment with low-dose cytarabine during past 2 years Investigational therapy within 4 weeks of starting ON 01910.Na
  • Psychiatric illness or social situation that limits the patient's ability to tolerate and/or comply with study requirements

Trial locations and contacts

87 sites in 6 countries.

87 sites in 6 countries

United States41 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21231

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75390

  • North Shore Medical Center

    Evanston, Illinois, 60201

  • Bon Secours St. Francois Health System

    Greenville, South Carolina, 29601

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Texas M. D. Anderson Cancer Center

    Houston, Texas, 77030

  • Integrated Community Oncology Network

    Jacksonville, Florida, 32256

  • University of California San Diego Moores Cancer Center

    La Jolla, California, 92093

  • North Shore - LIJ Health System

    Lake Success, New York, 11042

  • Cardinal Bernardin Cancer Center

    Maywood, Illinois, 60153

  • Innovative Medical Research of South Florida, Inc.

    Miami, Florida, 33169

  • Mount Sinai Comprehensive Cancer Centers

    Miami Beach, Florida, 33140

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Weill Cornell Medical College

    New York, New York, 10021

  • Mount Sinai Medical Center

    New York, New York, 10029

  • University of Oklahoma Health Science Center

    Oklahoma City, Oklahoma, 73104

  • Woodlands Medical Specialists

    Pensacola, Florida, 32503

  • University of Pennsylvania Health System

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Cancer Care Centers of South Texas

    San Antonio, Texas, 78229

  • Virginia G. Piper Cancer Center

    Scottsdale, Arizona, 85258

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Edward H. Kaplan MD & Associates

    Skokie, Illinois, 60076

  • Providence Cancer Center

    Southfield, Michigan, 48075

  • Stanford Cancer Center

    Stanford, California, 94305

  • Martin Memorial Cancer Center

    Stuart, Florida, 34994

  • Overlook Hospital

    Summit, New Jersey, 07901

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Cleveland Clinic Florida

    Weston, Florida, 33331

  • University of Kansas Medical Center

    Westwood, Kansas, 66205

Other trials in United States

France15 sites

  • CHU Angers Service de Medecine D - Maladies du Sang

    Angers, 49033

  • CHU Avignon Centre Hospitalier Henri Dufaut

    Avignon, 84000

  • Hôpital Avicenne Hématologie Clinique

    Bobigny, 93009

  • CHU Caen Hématologie Clinique

    Caen, 14000

  • CHU Estaing Service d'hématologie

    Clermont-Ferrand, 63000

  • CHU Lille Hôpital Claude Huriez

    Lille, 59037

  • CHU Limoges Hopital Dupuytren

    Limoges, 87042

  • Institute Paoli Calmettes

    Marseille, 13009

  • Hôpital de L'archet I

    Nice, 6202

  • Hôtel Dieu Sce Hématologie Clinique

    Paris, 75004

  • Hôpital Saint-Antoine

    Paris, 75571

  • CHU Perpignan Centre Hospitalier Hôpital Saint-Jean

    Perpignan, 66046

  • CRLCC Henri Becquerel

    Rouen, 76038

  • Chu-Strasbourg-Hopital Civil

    Strasbourg, 67091

  • Hôpital Purpan

    Toulouse, 31059

Other trials in France

Germany10 sites

  • Universitätsklinikum Bonn

    Bonn, North Rhine-Westphalia, 53127

  • Universitätsklinikum zu Köln

    Cologne, 50924

  • Universitätsklinikum Dresden

    Dresden, 01307

  • Heinrich-Heine-Universität Düsseldorf

    Düsseldorf, 40225

  • Klinikum der Johann Wolfgang-Goethe-Universität

    Frankfurt am Main, 60590

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universitätsmedizin Mannheim

    Mannheim, 68167

  • Johannes-Wesling-Klinikum Minden

    Minden, 32429

  • Klinikum Rechts der Isar der Technischen Universität München

    München, 81675

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Italy9 sites

  • Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo

    Alessandria, 15100

  • Azienda Ospedaliero-Universitaria di Bologa Policlinico S. Orsola-Malpighi

    Bologna, 40138

  • Azienda Ospedaliera-Universitairia Vittorio Emanuele-Ferrarotto-Santo Bambino

    Catania, 95124

  • Azienda Ospedaliera Universitaria Careggi di Firenze

    Florence, 50134

  • Azienda Ospedaliera Universitaria San Martino

    Genova, 16132

  • Azienda Osperdaliera Universitaria Maggiore della Carità

    Novara, 28100

  • Università degli Studi La Sapienza

    Roma, 00161

  • Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

    Siena, SI, 53100

  • Azienda Ospedaliero Universitaria San Giovanni Battista di Torino

    Torino, 10126

Other trials in Italy

Spain8 sites

  • Hospital Universitario La Princesa

    Madrid, 28006

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Clínico Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33006

  • Hospital Universitario Son Espases

    Palma de Mallorca, 07012

  • Hospital Clínico Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46009

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Belgium4 sites

  • Ziekenhuis Netwerk Antwerpen

    Antwerp, 2060

  • Universitair Ziekenhuis Gent

    Ghent, 9000

  • H. Hartziekenhuis Roeselare-Menen vzw

    Roeselare, West-vlaanderen, 8800

  • CHU de Mont-Godinne

    Yvoir, 5530

Other trials in Belgium

About this study

Official title: 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

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.

Read the detailed description

This is a Phase III open-label, randomized, controlled, multicenter study (up to 50 centers). Approximately 270 patients with MDS classified as RAEB-1 and RAEB-2 using the WHO classification and as RAEB-t and chronic myelomonocytic leukemia (CMML) using the FAB classification who failed, became intolerant to, or progressed after treatment with 5-azacitidine or decitabine administered during the past 2 years, will be randomized in a 2:1 ratio into the following 2 treatment regimens:

  • Best Supportive Care (BSC) + ON 01910.Na 1800 mg/24 hr administered as a 72-hr continuous intravenous (CIV) infusion on Days 1, 2, and 3 of a 2-week cycle (N = approximately 180 patients)
  • BSC (N = approximately 90 patients).

Patients will be stratified at entry by bone marrow (BM) blasts (5% to 19% vs. 20% to 30%). After completing the first eight 2-week cycles (i.e., after 16 weeks of treatment), the frequency of further 72-hr CIV infusions will be decreased to an administration on Days 1, 2, and 3 of a 4-week cycle.

Patients will remain treated on study until 2006 International Working Group (IWG) progression criteria are met (i.e., 50% increase of BM blasts or worsening of cytopenias) or until death from any cause, whichever comes first.

Patients who progress to Acute Myeloid Leukemia (AML) while on study should be offered either standard treatment for AML or enrollment in an appropriate investigational study if they are eligible. These treatments with their start and end dates should be documented and patient survival time will be documented for all randomized patients.

Cross-over of BSC patients to ON 01910.Na after progression will not be allowed. However, patients in the BSC-only group will be allowed, as medically justified, access to low-dose cytarabine 20 mg/m2 subcutaneously (SC) once daily for the first consecutive 14 days of each 28-day cycle, up to 4 cycles, until progression or unacceptable toxicity develops. Low-dose cytarabine will be delayed as needed until recovery of blood counts. All study participants will be allowed, as medically justified, access to RBC and platelet transfusions and to growth factors (erythropoietin, Filgrastim [G-CSF]). Hydroxyurea will be allowed to manage blastic crisis with hyperleukocytosis when patients transition to leukemia.

Being tested
ON 01910.Na
Keywords
Myelodysplastic syndromes, MDS
Medical subject headings
Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ON 01910.NaDrug

    Also called rigosertib

    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.

Study groups in NCT01241500
Study groupRoleWhat they receive
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).
Receives: Drug: ON 01910.Na
Best supportive care (BSC)No interventionPatients will receive best supportive care (BSC).

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 18 months

Secondary outcomes (8)

  1. Overall response (complete and partial remission) according to 2006 IWG criteria

    Compare the BSC + ON 01910.Na group to the BSC group with respect to changes in bone marrow myeloblasts, hemoglobin, peripheral neutrophils, platelets and blasts.

    Measured: Changes measured at Week 4 from Baseline and every 8 Weeks thereafter

  2. Complete bone marrow response according to 2006 IWG criteria

    Compare the BSC + ON 01910.Na group to the BSC group with respect to changes in bone marrow myeloblasts.

    Measured: Changes measured at Week 4 from Baseline and every 8 Weeks thereafter

  3. Hematological improvements according to 2006 IWG criteria

    Compare the BSC + ON 01910.Na group to the BSC group with respect to in absolute neutrophil count (ANC), platelet count, and erythroid responses.

    Measured: Weekly

  4. Scores of Quality of Life Questionnaire

    Compare the BSC + ON 01910.Na group to the BSC group with respect to scores of Quality-of-life (QOL)(using the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-C30 version 3.

    Measured: Measured at Baseline and every 4 Weeks

  5. Adverse events

    Record adverse events according to CTCAE v4.

    Measured: Weekly

  6. Change in Aneuploidy

    Improvements of cytogenetics as evaluated by the change in aneuploidy in bone marrow according to 2006 IWG criteria.

    Measured: Baseline and, only if abnormal at Baseline, Week 4 and every 8 Weeks thereafter

  7. Transition time to AML

    Transition time to AML: Defined for RAEB-1 and RAEB-2 MDS and chronic myelomonocytic leukemia (CMML) patients (with BM blasts from 10% to 20% for CMML) by an increase of at least 50% BM blasts and more than 20% BM blasts; Defined for RAEB-t by an increase of at least 50% BM blasts.

    Measured: Measured at Week 4 from date of randomization and every 8 Weeks thereafter

  8. Incidence of infections and bleeding episodes.

    Incidence of infections (treated with intravenous antimicrobials) and bleeding episodes.

    Measured: Every 4 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2010 (estimated)
  2. Study startNov 2010
  3. Primary completion3 Oct 2018
  4. Study completion3 Oct 2018

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
299 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01241500
Sponsor's protocol ID
04-21
Acronym
ONTIME
Status last verified
Jul 2018
First submitted
1 Nov 2010
Last updated
30 Jun 2020
Results posted
No
Data monitoring committee
Yes

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 21924492

  • 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.

    PubMed 27104980

  • 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.

    PubMed 26968357

  • 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.

    PubMed 27400247

  • Al-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

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ON 01910.Na in people with Myelodysplastic Syndromes and MDS, run by Traws Pharma, Inc. at 87 sites in 6 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 16 inclusion and 17 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 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 87 sites in United States, France, Germany, Italy, Spain and 1 more country. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Overall survival (time frame: Up to 18 months). 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 NCT01241500, which also lists 6 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 30 Jun 2020; AzTrials last refreshed its copy on 7 Nov 2026.

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