International study of Rigosertib versus doctorâ??s choice of treatment in patients suffering from Myelodysplastic Syndrome after Failure of a Hypomethylating Agent

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2018/06/014445
• Date of registration: 07-06-2018
• Prospective Registration: Yes
• Primary sponsor: Onconova Therapeutics Inc
• Public title: International study of Rigosertib versus doctorâ??s choice of treatment in patients suffering from Myelodysplastic Syndrome after Failure of a Hypomethylating Agent
• Scientific title: A Phase III, International, Randomized, Controlled Study of Rigosertib versus Physicianâ??s Choice of Treatment in Patients with Myelodysplastic Syndrome after Failure of a Hypomethylating Agent
• Date of first enrolment: 15-06-2018
• Target sample size: 360
• Recruitment status: Open to Recruitment
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26062
• Study type: Interventional
• Study design: Randomized, Parallel Group Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Open Label
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, Croatia, Czech Republic, Estonia, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States of America

Contacts

• Name: Dr Shariq Anwar
• Affiliation: JSS Medical Research India Private Limited

• Name: Dr Sonika Newar
• Affiliation: JSS Medical Research India Private Limited

Key inclusion & exclusion criteria

Inclusion criteria: Male and female patients with excess blasts of 5% to 30% who meet all of the following criteria are eligible:

1. 18-81 years of age;

2. Disease classification and cytogenetics confirmed within 8 weeks prior to or during screening as follows:

a. RAEB-1 per World Health Organization (WHO) MDS criteria (5% to <10% BM blasts)

b. RAEB-2 per WHO MDS criteria (10% to <20% BM blasts)

c. RAEB-t per modified French-American-British (FAB) classification (20% to 30% BM blasts)

3. At least one cytopenia (ANC < 1800/μL or platelet count < 100,000/μL or hemoglobin [Hgb] < 10 g/dL)

4. 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)

Or

Intolerance to AZA or DAC

5. Total duration of prior HMA therapy <= 9 months and/or total <= 9 cycles of prior HMA therapy in <= 12 months

6. 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

7. Has failed to respond to, relapsed following, not eligible for, or opted not to participate in allogeneic stem cell transplantation

8. Off all treatments for MDS (including AZA and DAC) for >= 4 weeks before randomization; growth factors (G-CSF, erythropoietin and TPO) and transfusions are allowed before and during the study as clinically indicated

9. Patients with 5q- syndrome should have failed to respond to or progressed on treatment with lenalidomide, where available and indicated

10. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

11. Willing to adhere to the prohibitions and restrictions specified in this protocol

12. Patient must sign an Informed Consent form indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study. In case a patient is incapable of giving consent, the patientâ??s legally authorized representative (as defined by local regulation) must give consent. However, should the patient in any manner indicate the will not to participate this takes precedence and must be respected.

Sweden Specific requirement: In case a patient is incapable of giving consent, in addition to the legally authorized representative, the patientâ??s next of kin must give consent to the participation of the patient.


Exclusion criteria: 1. Previous participation in a clinical study of IV or oral rigosertib; patients who failed screening for other rigosertib studies may be screened for participation in this study

2. Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside plus 2-3 days of an anthracycline, or high-dose cytarabine (HDAC)

3. Patient previously diagnosed with AML (defined as a bone marrow or peripheral blood blast percentage >30%)

4. 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.

5. 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

6. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure or unstable angina pectoris

7. Active infection not adequately responding to appropriate therapy

8. Total bilirubin >=1.5 mg/dL not related to hemolysis or Gilbertâ??s disease

9. Alanine transaminase (ALT)/aspartate transaminase (AST) >=2.5 x upper limit of normal (ULN)

10. Serum creatinine >=2.0 mg/dL or eGFR (estimated Glomerular Filtration Rate) <40 mL/min.

11. Known active HIV, hepatitis B or hepatitis C, where active is defined as follows: a. HIV or Hepatitis C â?? presence of viral load b. Hepatitis B â?? antigen positive

12. Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)

13. 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 (β-HCG) pregnancy test at Screening

14. 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:

â?? estrogen-gestagen based contraceptives associated with inhibition of ovulation (oral, intravaginal, transdermal),

â?? gestagen only based contraceptives associated with inhibition of ovulation (oral, injectable, implantable),

â?? intrauterine devices (IUDs),

â?? intra-uterine hormone-releasing systems (IUSs),

â?? bilateral tubal occlusion

â?? vasectomized partner

â?? sexual abstinence in accordance with an individualâ??s lifestyle

15. Major surgery without full recovery or major surgery within 3 weeks before planned randomization

16. Uncontrolled hypertension

17. New onset seizures (within 3 months before planned randomization) or poorly controlled seizures

18. 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)

19. 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

20. Investigational therapy within 4 weeks of planned randomization

21. Psychiatric illness or social situation that would limit the patientâ??s

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: C469- Kaposis sarcoma, unspecified

Intervention(s)

Intervention1: Rigosertib Sodium: A sterile concentrated
solution to be diluted in 0.9% sodium chloride for injection just prior to infusion with a dose: 1800 mg/24 hr as 72-hr CIV infusion every other week for the first eight 2-week cycles (ie, 16 weeks, if no dose delays), then every 4 weeks afterward for total 6 months.
The further duration of the therapy depends on disease progression
Control Intervention1: Physicianâ??s choice of alternative treatment: Any approved or standard-of-care therapy

Primary Outcome(s)

1. Overall survival of all randomized patients (ITT population)

2. Overall survival of patients scored as IPSS-R very high riskTimepoint: End of study

Secondary Outcome(s)

Safety Endpoints:

â?¢ Worst-grade adverse events (AEs)

â?¢ Deaths, other serious AEs, and other AEs leading to discontinuation of study treatment

â?¢ Worst-grade laboratory abnormalities

Timepoint: End of study

Efficacy Endpoints:

â?¢ Overall survival of patients with monosomy 7 chromosomal aberrations

â?¢ Overall survival of patients with trisomy 8 chromosomal aberrations

â?¢ Overall response rate according to 2006 IWG criteria

â?¢ Quality-of-life scores using the EuroQol EQ-5D Questionnaire

â?¢ Bone marrow blast response rate according to 2006 IWG criteria

â?¢ Hematologic improvement (erythroid, platelet, or neutrophil response rates) according to 2006 IWG criteria

Timepoint: End of study

Secondary ID(s)

04-30, Version No. 5.0 date 21-Feb-2018

Source(s) of Monetary Support

Onconova Therapeutics, Inc. 375 Pheasant Run Newtown, PA 18940 (USA)

Ethics review

Status: Approved
Approval date: 28/05/2018
Contact:

Sahyadri Hospitals Ltd Ethics Committee, Pune

Status: Not Approved
Approval date:
Contact:

Ethics Committee Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata

Status: Not Approved
Approval date:
Contact:

Ethics Committee of Care Institute of Medical Sciences,Ahmedabad

Status: Not Approved
Approval date:
Contact:

Ethics Committee Silver, CMC, Tamilnadu

Status: Not Approved
Approval date:
Contact:

Fortis Hospital Ethics Committee, Bangalore

Status: Not Approved
Approval date:
Contact:

Human Ethics Committee, Tata Memorial Centre, Mumbai

Status: Not Approved
Approval date:
Contact:

Institutional Ethics committee, IHTM, Kolkata

Status: Not Approved
Approval date:
Contact:

Institutional Ethics committee, Jaslok Hospital& Research Centre, Mumbai