Clinical Trial: Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official 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 Blast

Brief Summary: This study will examine the effect intravenously administered rigosertib has on the relationship between bone marrow blasts response and overall survival in myelodysplastic syndromes (MDS) patients who have 5-30% bone marrow blasts and who progressed on or after treatment with azacitidine or decitabine.

Detailed Summary:
Sponsor: Onconova Therapeutics, Inc.

Current Primary Outcome: Relationship of bone marrow blast response and overall survival. [ Time Frame: Up to 2 years. ]

Bone marrow blast response is defined as bone marrow (BM) complete response, ≥ 50% BM blast decrease from pretreatment value, or stable BM response (no progression) according to the International Working Group (IWG) 2006 criteria. Overall survival is defined as the time from first study treatment to death from any cause. All patients will be followed until death and/or progression, even if they have discontinued treatment for whatever cause. Survival time of patients lost to follow-up will be censored at the time they were last known to be alive.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of patients with overall hematologic response. [ Time Frame: Up to 2 years after study enrollment. ]
    Overall hematologic response (complete remission [CR], partial remission [PR], bone marrow complete response [BMCR], and stable disease [SD]) is defined according to 2006 International Working Group (IWG) response criteria.
  • Number of patients with hematological improvement. [ Time Frame: Up to 2 years after study enrollment. ]
    Hematological improvement (erythroid response, platelet response and neutrophil response) is defined according to 2006 International Working Group (IWG) response criteria.
  • Number of patients with cytogenetic response. [ Time Frame: Up to 2 years after study enrollment. ]
    Cytogenetic response is defined according to 2006 International Working Group (IWG) response criteria.
  • Progression-free survival. [ Time Frame: Up to 2 years after study enrollment. ]
    Progression-free survival is defined as time from date of first dose until date when progression is documented. Progression is defined according to 2006 International Working Group (IWG) response criteria.
  • Number of patients who transition to Acute Myeloid Leukemia (AML) [ Time Frame: Up to 2 years after study enrollment. ]
    Participants who progress to Acute Myeloid Leukemia (AML) during the study. AML is defined as an increase of at least 50% bone marrow blasts, and more than 20% bone marrow blasts for Refractory Anemia with Excess Blasts types 1 and 2 (RAEB-1 and RAEB-2) and Chronic Myelomonocytic Leukemia (CMML) patients and as an increase of at least 50% bone marrow blasts for Refractory Anemia with Excess Blasts in Transformation (RAEB-t) patients.
  • Quality of Life Questionnaire [ Time Frame: Up to 2 years after study enrollment. ]
    Change from baseline in responses in the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-C30 version 3. Questionnaire will be administered at baseline and at 4 week intervals.
  • Infections. [ Time Frame: Up to 2 years after study enrollment. ]
    Incidence of infections requiring treatment with intravenous antimicrobials and of bleeding episodes.
  • Concentration of rigosertib in plasma. [ Time Frame: Week 1 and week 3. ]
    Concentration of rigosertib in plasma will be measured by a validated High Performance Liquid Chromatography (HPLC) method.
  • Safety. [ Time Frame: Study enrollment until 30 days after patient's last dose of rigosertib up to 2 years. ]
    Counts of patients who have adverse events (AEs). Adverse events will be grouped by system organ class (SOC) and preferred term (PT) using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA), and will be summarized by worst grade according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.


Original Secondary Outcome: Same as current

Information By: Onconova Therapeutics, Inc.

Dates:
Date Received: August 21, 2013
Date Started: August 2013
Date Completion: December 2017
Last Updated: March 28, 2017
Last Verified: March 2017