NCT02562443

Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA

A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 372 (actual)
• Sponsor: Traws Pharma, Inc. · Industry
• Sex: All
• Age: 18 Years – 81 Years
• Healthy volunteers: Not accepted

Summary

The study's primary objective \[in a population of patients with MDS after failure of treatment with azacitidine (AZA) or decitabine (DAC)\], is to compare the overall survival (OS) of patients in the rigosertib group vs the Physician's Choice group, in all patients and in a subgroup of patients with IPSS-R very high risk.

Detailed description

This is a Phase III, open-label, randomized, controlled, international study. Approximately 360 patients \< 82 years of age with MDS classified as RAEB-1, RAEB-2, or RAEB-t who received AZA or DAC for ≤ 9 months and/or ≤ 9 cycles over 12 months and had their last dose of AZA or DAC within 6 months prior to screening will be stratified by: * Very high risk (VHR) vs non-VHR per IPSS-R, and * Geographic region (North America vs Europe vs Asia; because approved products and standard of care may vary by region), and randomly assigned in a 2:1 ratio to one of the following 2 treatment groups: * Rigosertib 1800 mg/24 hr administered as a 72 hr CIV infusion on Days 1, 2, and 3 of a 2 week cycle for the first 8 cycles, and on Days 1, 2, and 3 of a 4-week cycle thereafter (N = approximately 240 patients); * Physician's Choice of alternative treatment, which may include any approved or standard-of-care therapy that the patient has not shown to be hypersensitive to, based on frequently used treatment for MDS, as per institutional guidelines, after receipt of HMAs (N = approximately 120 patients). The drugs used in the Physician's Choice arm should be used according to the recommendations, if clinically appropriate, provided in the corresponding Summary of Product Characteristics (SmPC) and Prescribing Information of these drugs. Experimental therapies are not allowed on the PC arm. Patients will be treated until 2006 IWG progression criteria are met (ie, 50% increase of BM blasts or worsening of cytopenias) or until an unacceptable toxicity or intolerance. For all randomized patients who discontinue study treatment, subsequent therapies with their start and end dates, as well as survival time after treatment discontinuation, will be documented at least monthly until death. Patients in the PC group who progress will not be allowed to cross over to rigosertib. All patients in both treatment groups will be allowed, as medically justified, access to RBC and platelet transfusions and to growth factors (granulocyte colony-stimulating factor (G-CSF), erythropoietin, and thrombopoietin).

Conditions

• Myelodysplastic Syndrome
• MDS
• Refractory Anemia With Excess Blasts
• RAEB

Interventions

Type	Name	Description
DRUG	rigosertib	Patients will receive intravenous rigosertib 1800 mg/24 hr for 3 days every 2 weeks for first 8 cycles, then every 4 weeks thereafter + best supportive care (BSC).
DRUG	Any approved or standard-of-care therapy	Patients will receive Physician's Choice of Treatment or alternative treatment which may include any approved or standard-of-care therapy, based on frequently used treatment for MDS (no experimental therapy) + best supportive care.
DRUG	best supportive care (BSC)	Patients will receive best supportive care (BSC): azacitidine (AZA) and/or decitabine (DAC) are permitted.
DRUG	best supportive care (BSC)	Patients will receive best supportive care (BSC).

Timeline

• Start date: 2015-12-02
• Primary completion: 2020-07-26
• Completion: 2021-07-26
• First posted: 2015-09-29
• Last updated: 2022-09-26

Locations

158 sites across 22 countries: United States, Australia, Austria, Belgium, Canada, Croatia, Czechia, Estonia, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Poland, Russia, Spain, Sweden, Switzerland, United Kingdom