Study of 72-Hour Infusion of ON 01910.Na in Patients With MDS or AML
Acute Myeloid Leukemia
Drug: ON 01910.Na
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1/2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)|
- Response as defined per the 2000 International Working Group (IWG) Criteria in patients with MDS. [ Time Frame: 6 -12 months ] [ Designated as safety issue: No ]
- Hematologic improvement. [ Time Frame: 6 - 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||February 2014|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: ON 01910.Na
1800 mg/day of ON 01910.Na administered as a 24-hour continuous intravenous infusion on days 1, 2 and 3 of 14-day cycle.
Drug: ON 01910.Na
1800 mg/day as a 24-hour continuous intravenous infusion administered three times a week every 2 weeks
The primary objective of this study is to evaluate the efficacy and safety of ON 01910.Na CIV 24-hour infusion administered three times a week every other week in achieving by week 25 a complete or partial response as defined per the 2000 International Working Group (IWG) Criteria in patients with MDS or as defined by Cheson et al. [JCO 21:4642 (2003)] in patients with AML.
The secondary objectives are to assess:
- Time and duration of response
- Blastic response in bone marrow
- Improvement of dyspoiesis as evaluated by the change in aneuploidy in bone marrow
- Change in International Prognostic Scoring System (IPSS) in MDS patients
- Major and minor responses in absolute neutrophil count, according to IWG 2000 criteria
- Major and minor responses in platelet count, according to IWG 2000 criteria
- Major and minor erythroid response, according to IWG 2000 criteria
- Time to progression
- Overall survival at 25 and 50 weeks
- Proportion of MDS patients transitioning to acute myeloid leukemia (AML) at 25 and 50 weeks
This is a phase 1/2 single arm study in which six to thirty-five patients with MDS or AML who meet all other inclusion/exclusion criteria will receive ON 01910.Na as an intravenous continuous infusion (IVCI) over 72 hours once a week every other week.
In the phase 1 portion of the study, a traditional dose escalation rule, also known as the "3+3" rule, will be used. Three patients will be treated at the 800 mg/m2/day dose level. If none of the patients experience a DLT during cycle 1, the next group of 3 patients will receive 1500 mg/m2/day. If no DLT is seen at the 1500 mg/m2/day dose level, then the dose used in the phase 2 portion of the study will be 1500 mg/m2/day. If there is DLT in one of the first three patients at the 800 mg/m2/day dose level, this dose level will be expanded to 6 patients. If ≤ 1 patient out of 6 experience DLT, then the dose will be escalated to the 1500 mg/m2/day dose level. If ≥ 2 patients experience DLT at the 800 mg/m2/day dose level, a full safety review will determine if further enrollment of patients will proceed. If there is DLT in one of the first three patients at the 1500 mg/m2/day dose level, this dose level will be expanded to 6 patients. If ≤ 1 patient out of 6 experience DLT at the 1500 mg/m2/day dose level, then 1500 mg/m2/day dose level will be considered the MTD. If ≥ 2 patients experience DLT at the 1500 mg/m2/day dose level, then 800 mg/m2/day will be designated as the MTD.
The total study duration is 29 weeks, which includes a 2-week screening phase, a 23-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 and followed up.
Patients who achieve by week 25 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 for 72 h once a week every 2 weeks and will be followed up.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00854945
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Azra Raza, MD||Columbia University|