Trial Review

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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
NA
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
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents


Results not provided in https://clinicaltrials.gov/study/NCT01928537