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)
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response as defined per the 2000 International Working Group (IWG) Criteria in patients with MDS.
6 -12 months
Azra Raza, MD
United States: Food and Drug Administration
|Columbia University Medical Center||New York, New York 10032|