Conditions: Relapsed/Refractory Leukemia
Keywords: Tumor Leukemia Plitidepsin Aplidin
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
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.

Detailed description:
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.

Arms:
arm 1: Plitidepsin in combination with Cytarabine

Interventions: intervention 1: Plitidepsin plus Cytarabine
Intervention descriptions: intervention 1: Plitidepsin 0.54 mg /m2 (initial dose)daily x 5 one hour infusion every 3 weeks plus Cytarabine 1 g/m2 daily for 5 days.

Protocol document: