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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01928537




Registration number
NCT01928537
Ethics application status
Date submitted
21/08/2013
Date registered
26/08/2013
Date last updated
30/06/2020

Titles & IDs
Public title
Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine
Scientific title
Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients With Myelodysplastic Syndrome With Excess Blasts Progressing On or After Azacitidine or Decitabine
Secondary ID [1] 0 0
2013-001124-19
Secondary ID [2] 0 0
Onconova 04-24
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Refractory Anemia With Excess Blasts 0 0
Chronic Myelomonocytic Leukemia 0 0
Cytopenia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Other blood disorders
Blood 0 0 0 0
Anaemia
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: rigosertib sodium - Rigosertib sodium will be administered as a 72-hr continuous intravenous infusion consisting of 3 consecutive doses of 1800 mg over 24 hours on Days 1, 2, and 3 of a 14-day cycle for the first 8 cycles and then on Days 1, 2, and 3 of a 28-day cycle for the following cycles.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relationship of bone marrow blast response and overall survival.
Timepoint [1] 0 0
Up to 2 years.
Secondary outcome [1] 0 0
Number of patients with overall hematologic response.
Timepoint [1] 0 0
Up to 2 years after study enrollment.
Secondary outcome [2] 0 0
Number of patients with hematological improvement.
Timepoint [2] 0 0
Up to 2 years after study enrollment.
Secondary outcome [3] 0 0
Number of patients with cytogenetic response.
Timepoint [3] 0 0
Up to 2 years after study enrollment.
Secondary outcome [4] 0 0
Progression-free survival.
Timepoint [4] 0 0
Up to 2 years after study enrollment.
Secondary outcome [5] 0 0
Number of patients who transition to Acute Myeloid Leukemia (AML)
Timepoint [5] 0 0
Up to 2 years after study enrollment.
Secondary outcome [6] 0 0
Quality of Life Questionnaire
Timepoint [6] 0 0
Up to 2 years after study enrollment.
Secondary outcome [7] 0 0
Infections.
Timepoint [7] 0 0
Up to 2 years after study enrollment.
Secondary outcome [8] 0 0
Concentration of rigosertib in plasma.
Timepoint [8] 0 0
Week 1 and week 3.
Secondary outcome [9] 0 0
Safety.
Timepoint [9] 0 0
Study enrollment until 30 days after patient's last dose of rigosertib up to 2 years.

Eligibility
Key inclusion criteria
* Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or French-American-British (FAB) classification.
* MDS classified as follows, according to WHO criteria and FAB classification:

* RAEB-1 (5% to 9% BM blasts)
* RAEB-2 (10% to 19% BM blasts)
* CMML (10% to 20% BM blasts) and white blood cells (WBC) < 13,000/µL
* RAEB-t (20% to 30% BM blasts), meeting the following criteria: WBC < 25,000/µL at study entry; or, Stable White Blood Cell (WBC) at least 4 weeks prior to Screening and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukopheresis.
* At least one cytopenia (Absolute Neutrophil Count (ANC) < 1800/µL or Platelet (PLT) count < 100,000/µL or hemoglobin (Hgb) < 10 g/dL).
* Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows:

* For patients with ? 5% BMBL, = 50% increase in BMBL to ? 5% BMBL
* For patients with 5-10% BMBL, = 50% increase in BMBL to ? 10% BMBL
* For patients with 10-20% BMBL, = 50% increase in BMBL to ? 20% BMBL
* For patients with 20-30% BMBL, = 50% increase in BMBL to ? 30% BMBL
* Any of the following: = 50% decrease from maximum remission/response levels in granulocytes or PLT; Decrease in Hgb concentration by = 2 g/dL; or, Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values ? 9 g/dL prior to transfusion to be considered), in the absence of another explanation.
* Has failed to respond to, relapsed following, not eligible, or opted not to participate in bone marrow transplantation.
* Off all other treatments for MDS for at least 4 weeks, except for azacitidine or decitabine. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated.
* No medical need for induction chemotherapy.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
* Willing to adhere to the prohibitions and restrictions specified in this protocol.
* Patient must signed an informed consent form.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous participation in a clinical study of IV or oral rigosertib.
* Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] 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.
* Active infection not adequately responding to appropriate therapy.
* Total bilirubin = 1.5 mg/dL not related to hemolysis or Gilbert's disease.
* ALT/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).
* Female patients who are pregnant or lactating.
* Patients who are unwilling to follow strict contraception requirements.
* Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (ßHCG) pregnancy test at Screening.
* Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 visit.
* Uncontrolled hypertension (defined as a systolic pressure =160 mmHg and/or a diastolic pressure = 110 mmHg).
* New onset seizures (within 3 months prior to Baseline) or poorly controlled seizures.
* Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
* Prior treatment with low-dose cytarabine during the past 2 years.
* Investigational therapy within 4 weeks of Baseline/Day 1 visit.
* Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/06/2017
Sample size
Target
Accrual to date
Final
67
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Monash Health, Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Center - East Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Denmark
State/province [9] 0 0
Hovedstaden
Country [10] 0 0
Denmark
State/province [10] 0 0
Jylland
Country [11] 0 0
France
State/province [11] 0 0
IDF
Country [12] 0 0
France
State/province [12] 0 0
Marseille
Country [13] 0 0
Germany
State/province [13] 0 0
Hessen
Country [14] 0 0
Germany
State/province [14] 0 0
Dresden
Country [15] 0 0
Germany
State/province [15] 0 0
Düsseldorf
Country [16] 0 0
Germany
State/province [16] 0 0
Göttingen
Country [17] 0 0
Germany
State/province [17] 0 0
Köln
Country [18] 0 0
Germany
State/province [18] 0 0
München
Country [19] 0 0
Italy
State/province [19] 0 0
Firenze
Country [20] 0 0
Italy
State/province [20] 0 0
Novara
Country [21] 0 0
Italy
State/province [21] 0 0
Rome
Country [22] 0 0
Spain
State/province [22] 0 0
Salamanca
Country [23] 0 0
Sweden
State/province [23] 0 0
Skåne
Country [24] 0 0
Sweden
State/province [24] 0 0
Västra Götalandsregionen
Country [25] 0 0
Sweden
State/province [25] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Traws Pharma, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will examine the effect intravenously administered rigosertib has on the relationship between bone marrow blasts response and overall survival in myelodysplastic syndromes (MDS) patients who have 5-30% bone marrow blasts and who progressed on or after treatment with azacitidine or decitabine.
Trial website
https://clinicaltrials.gov/study/NCT01928537
Trial related presentations / publications
Olnes MJ, Shenoy A, Weinstein B, Pfannes L, Loeliger K, Tucker Z, Tian X, Kwak M, Wilhelm F, Yong AS, Maric I, Maniar M, Scheinberg P, Groopman J, Young NS, Sloand EM. Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. Leuk Res. 2012 Aug;36(8):982-9. doi: 10.1016/j.leukres.2012.04.002. Epub 2012 Apr 21.
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.
Silverman LR, Greenberg P, Raza A, Olnes MJ, Holland JF, Reddy P, Maniar M, Wilhelm F. Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy. Hematol Oncol. 2015 Jun;33(2):57-66. doi: 10.1002/hon.2137. Epub 2014 Apr 29.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Steven M. Fruchtman, MD
Address 0 0
Traws Pharma, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01928537