INSPIRE

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

Objective

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.

Study Arms

  • Experimental: rigosertib + best supportive care (BSC)
  • Active Comparator: Physician's Choice (PC) + best supportive care (BSC)

Eligibility

  • MDS classified as follows:
    • RAEB-1 per World Health Organization (WHO) MDS criteria (5% to <10% BM blasts)
    • RAEB-2 per WHO MDS criteria (10% to <20% BM blasts)
    • RAEB-t per French-American-British (FAB) classification (20% to 30% BM blasts)
  • At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin [Hgb] < 10 g/dL)
  • 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)
  • Duration of prior HMA therapy ≤ 9 months and/or total ≤ 9 cycles of prior HMA therapy in ≤ 12 months
  • 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
  • Has failed to respond to, relapsed following, not eligible for, or opted not to participate in allogeneic stem cell transplantation
  • Off all treatments for MDS (including AZA and DAC) for ≥ 4 weeks before randomization; growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

NCT ID

NCT02562443