Clinical Study of PM01183 in Patients With Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome
|Acute Leukemia||Drug: PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
|Official Title:||Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of Lurbinectedin (PM01183) in Patients With Advanced Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome.|
- Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of PM01183 in patients with advanced acute leukemia. [ Time Frame: Up to 30 months ]The recommended dose (RD) will be the immediate lower DL below the MTD (maximum tolerated dose)with less than 1/3 of the first 6 evaluable patients experiencing DLT (dose limiting toxicity)during the induction, provided the RD is ≥ dose level 2. If the RD is determined at dose level 1, no further expansion will be done, and the study will be terminated.
- Antileukemic activity [ Time Frame: After induction/reinduction and every 4 weeks after treatment discontinuation; up to 30 months ]Activity will be defined according to the International Working Group (IWG) criteria.
- Pharmacogenomic (PGx) profile of PM01183 in patients with advanced acute leukemia. [ Time Frame: Between day -24 to day 1 ]Identification of potential biomarkers of response to PM01183
- Pharmacokinetics (PK) of PM01183 in patients with advanced acute leukemia [ Time Frame: Days 1 to 8 of induction and day 1 of next phase ]The PK will be elucidated using standard non-compartmental methods. The following parameters will be calculated: maximum drug concentration (Cmax), area under the curve (AUC), volume of distribution based on the terminal half-life (Vz), volume of distribution at steady state (Vss), clearance (CL) and half-life (t1/2)
|Study Start Date:||May 2011|
|Study Completion Date:||July 2015|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
PM01183 will be administered i.v. as a 1-hour infusion through a pump device at escalating doses according to the respective dose level, on Days 1 and 8 of each treatment phase.
Drug: PM01183 1 mg Powder for concentrate for solution for infusion and PM01183 4 mg Powder for concentrate for solution for infusion
PM01183 Drug Product will be provided as a lyophilized powder for concentrate for solution for infusion with a strength of 1.0 mg/vial and 4.0 mg/vial.
Before use, the vials will be reconstituted with 2 ml or 8 ml of sterile water for injection to give a solution containing 0.5 mg/ml of PM01183.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01314599
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Texas|
|Houston, Texas, United States, 77030|