Study of 72-Hour Infusion of ON 01910.Na in Patients With MDS or 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
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.