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
This is a Phase III, open-label, randomized, controlled, international study (approximately
100 sites). Approximately 225 patients < 80 years of age with MDS classified as RAEB-1,
RAEB-2, or RAEB-t who received AZA or DEC for ≤ 9 months and had their last dose of AZA or
DEC 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 150 patients);
- Physician's Choice of alternative treatment, which may include any approved or
standard-of-care therapy, based on frequently used treatment for MDS after receipt of
HMAs (N = approximately 75 patients). Experimental therapies are not allowed on the PC
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).