Initial Evaluation of a 48-h Continuous Intravenous Infusion Weekly Regimen of ON 01910.Na in Advanced Myelodysplastic Syndrome (MDS).

Abstract

3815 Poster Board III-751 Following initial promising clinical results reported at ASH 2008 (Shenoy et al) in RAEB MDS and AML patients treated with the new investigational agent ON 01910.Na, we have initiated a phase 1/2 single arm escalating dose study in advanced MDS patients with a shorter schedule of administration of ON 01910.Na. The first 13 patients enrolled in our ongoing trial (6 high risk, 1 Intermediate-2 and 5 Intermediate-1 according to IPSS classification; 7 females/6 males, age range: 47-83ys), most of them having failed prior MDS therapies were administered ON 01910.Na as a 48 h continuous intravenous infusion weekly for 3 weeks of a 4-week cycle. Ten patients were treated at the 800 mg/m2/day dose level and 3 at the 1500 mg/m2/day dose level for 4 to 27+ weeks (1 to 6 four-week cycles). Most patients had grade 3 or 4 cytopenias at baseline. Overall the therapy was well tolerated and a few patients reported improvements of well being and pain relief. The most frequently reported adverse events were thrombocytopenia, neutropenia, anemia, fatigue and nausea. Serious adverse events were typical of this patient population and none of them was related to ON 01910.Na except for one case of neutropenia. Bone marrow blastic response was evaluated by bone marrow morphology. Five patients had a pretreatment blast count lower than 5% and no worsening of blast count was observed in the 3 patients who had follow-up bone marrow examination. Another six patients had more than 5% pretreatment bone marrow blasts. Among these patients, two had significant decreases in blast counts compared to pre-treatment values, while two showed stabilization and two progressed. Two patients had hematological improvements (neutrophil and erythroid responses). These results are encouraging and the trial is continuing. Patient Bone Marrow Blasts Hematological Improvement Pre-Treatment 4-8 week Follow-up 1 <2% 2% 2 10-13% Death end 1st cycle 3 1-2% Not Done (Platelet =4) 4 20-30% 30% N wk 10-18 5 <5% 3% 6 3% Death end 2nd cycle 7 <5% 1-2% 8 25% 11% 9 10-13% 15%* E wk 1-13 10 35% Discontinued mid 2nd cycle (transplant) 11 9% 5% 12 10% 2% 13 15% 20% * 16 week Follow-up: 25% blasts Disclosures: Wilhelm: Onconova: Employment.