Clinical Study of Plitidepsin (Aplidin®) in Combination With Cytarabine in Patients With Relapsed/Refractory Leukemia

This is a Phase I/II study to determine:

• the safety, tolerability and to identify the MTD and DLT of Plitidepsin in combination with a fixed dose of Cytarabine in patients with relapsed/refractory leukemia and to determine the response rate of the combination of Plitidepsin with Cytarabine in patients with relapsed/refractory AML treated at the MTD.
• the pharmacokinetic parameters of Plitidepsin in combination with Cytarabine.
• whether Plitidepsin in combination with Cytarabine exerts antiangiogenic effects as measured by reduction in microvessel density and VEGFR-1 expression in bone marrow biopsies of patients with relapsed/refractory leukemia.
• whether measurement of free serum VEGF levels, soluble circulating VEGF Receptor and Peripheral Progenitor Endothelial cells provide an early marker of response to Plitidepsin.
• the effects of Plitidepsin and Cytarabine on cytidine deaminase activity and correlate results with Cytarabine drug resistance.
• changes in leukemic gene expression as a result of Plitidepsin and Cytarabine administration.
• tumor response duration.
• progression free survival and overall survival.