Clinical Trial: Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Myelodysplastic Syndrome Patients With

Brief Summary: This study will explore the efficacy and safety of a regimen of ON 01910.Na as a 48-hour continuous intravenous infusion once a week for 3 weeks of a 4-week cycle in MDS patients with Trisomy 8 or classified as Intermediate-1, -2 or High Risk who are not responding to current therapeutic options. The rationale for this trial is based upon data from laboratory studies with ON 01910.Na and upon activity that has been observed in other clinical trials with ON 01910.Na in patients with MDS.

Detailed Summary: This is a phase 2, study in which 14 MDS patients with Trisomy 8 or classified as Intermediate-1, -2 and High risk who meet all other inclusion/exclusion criteria will receive ON 01910.Na 800 mg/m^2/24h as an continuous intravenous infusion (CIV) over 48 hours once a week for 3 weeks of a 4-week cycle. As of Amendment 3 to the Protocol, the regimen is changed to 1800 mg/24h for 72 hours every other week for the first four 2-week cycles and every 4 weeks afterwards. The total study duration is 31 weeks, which includes a 2-week screening phase, a 27-week dosing phase, and a 4-week follow-up phase that begins after the last dose of ON 01910.Na. Beginning at week 4, and every 2 weeks thereafter, patients will be assessed for response. Patients who drop out for any reason will not be replaced. Patients who achieve by week 29 a complete or partial response or stabilization of their disease are eligible to receive an additional 24 weeks of ON 01910.Na 1800 mg/24 h over 72 hours per week of a 4-week cycle.
Sponsor: Onconova Therapeutics, Inc.

Current Primary Outcome:

• Overall Response Rate (ORR) [ Time Frame: 29 weeks ]
  The Overall Response Rate is defined as the proportion of patients who achieve a Complete Response, a Partial Response, A Complete Bone Marrow Response or a Hematologic Improvement (HI) according to the 2006 International Working Group (IWG) criteria.
• Number of patients with adverse events [ Time Frame: From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks ]
  The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 will be used to determine the grade of adverse events.

Original Primary Outcome: Complete or partial response as defined per the 2006 International Working Group (IWG) Criteria [ Time Frame: 29 weeks ]

Current Secondary Outcome:

• Time to Overall Response [ Time Frame: 29 weeks ]
  Time to Overall Response is calculated from date of first study drug administration to date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria.
• Duration of Response [ Time Frame: 29 weeks ]
  Duration of response is calculated from date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria) until the date of disease progression. Patients who did not have disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
• Bone Marrow Complete Response [ Time Frame: Weeks 5, 13, 21 and 29 ]
  The proportion of patients who achieve a Bone Marrow Complete Response (BMCR) according to 2006 International Working Group (IWG) criteria. Bone marrow blasts are determined in bone marrow differential count.
• Cytogenetic Response [ Time Frame: 29 weeks ]
  Cytogenetic Response is defined as the number of patients who achieve a cytogenic response according to 2006 International Working Group criteria. Complete response is defined as the disappearance of the chromosomal abnormality without appearance of new ones. Partial response is defined as at least 50% reduction of the chromosomal abnormality.
• Neutrophil Response [ Time Frame: 29 weeks ]
  The number of patients who achieve a Neutrophil Response according to 2006 International Working Group (IWG). Neutrophil Response is defined as at least a 100% increase and an absolute increase greater than 0.5 x 10^9/L. Pretreatment values must be less than 1.0 x 10^9/L.
• Platelet Response [ Time Frame: 29 weeks ]
  The number of patients who achieve a Platelet Response according to 2006 International Working Group (IWG). Platelet Response is defined as an absolute of greater than or equal to 30 x 10^9 for patients starting with less than 20 x 10^9/L. increase and an absolute increase greater than 0.5 x 10^9/L. Pretreatment values must be less than 1.0 x 10^9/L.
• Erythroid Response [ Time Frame: 29 weeks ]
  The number of patients who achieve an Erythroid Response according to 2006 International Working Group (IWG). Erythroid Response is defined as a Hgb increase equal to or greater than 1.5 g/dL and a relevant reduction of units of red blood cells (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 wells. Only RBC transfusions given for a Hgb of 9.0 g/dL or lower pretreatment will count in the RBC transfusion response evaluation. Pretreatment values of Hgb must be lower than 11 g/dL.
• Time to Disease Progression [ Time Frame: 29 weeks ]
  Time to Disease Progression is calculated from date of first dose of study drug administration to date of disease progression recorded on the hematology response assessment clinical report form.
• Time to Acute Myeloid Leukemia (AML) Progression [ Time Frame: 29 and 53 weeks ]
  Time to Acute Myeloid Leukemia (AML) Progression is calculated from date of first study drug administration to date of AML progression recorded on the Off Study Summary clinical report form. Patients who do not have AML disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
• Overall Survival [ Time Frame: 29 and 53 weeks ]
  Overall Survival is calculated from date of first study drug administration to date of death. In event of no death prior to study termination or data analysis cutoff, overall survival is censored at the last known date patient was alive
• Proportion of patients who achieve a Complete Hematologic Response [ Time Frame: Up to 29 weeks ]
  The proportion of patients who achieve a Complete Remission (CR) Hematologic Response according to 2006 International Working Group (IWG) criteria. Bone marrow blasts are determined in bone marrow differential count.
• The proportion of patients who achieve a Partial Remission (CR) [ Time Frame: Up to 29 weeks ]
  The proportion of patients who achieve a Partial Remission (PR) Hematologic Response according to 2006 International Working Group (IWG) criteria. Bone marrow blasts are determined in bone marrow differential count.

Original Secondary Outcome:

• Time and duration of overall response [ Time Frame: 29 weeks ]
• Change in International Prognostic Scoring System (IPSS) risk category [ Time Frame: 29 weeks ]
• Hematologic Improvement according to IWG 2006 criteria [ Time Frame: 29 weeks ]

Dates:
Date Received: May 19, 2009
Date Started: May 2009
Date Completion:
Last Updated: August 1, 2016
Last Verified: August 2016