This study aim is to assess, if treosulfan pharmacokinetics are influenced by declined renal function and by race/ethnicity of patients. The study also aims to determine an appropriate safe dose of treosulfan, when patient's renal function is impaired. The participants of this study are undergoing allogenic hematopoietic stem cell transplantation for treatment of acute myeloid leukemia or myelodysplastic syndrome.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
36
IV infusion
IV infusion
University of Illinois
Chicago, Illinois, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
WITHDRAWNThe Ohio State University
Columbus, Ohio, United States
RECRUITINGVCU Massey Cancer Center
Richmond, Virginia, United States
RECRUITINGArea Under the Concentration-time Curve From Time of Administration to the Last Measurable Concentration (AUClast) for Treosulfan
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Area Under the Concentration-time Curve From Time of Administration to Time of Infinity (AUCinf) for Treosulfan
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Maximum Observed Plasma Concentration (Cmax) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Area Under the Concentration-time Curve From Time of Administration to the Last Measurable Concentration (AUClast) for Treosulfan Metabolite (Treosulfan Monoepoxide)
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Area Under the Plasma Concentration-time Curve From Time of Administration to Time of Infinity (AUCinf) for Treosulfan Metabolite (Treosulfan Monoepoxide)
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Time to Last Quantifiable Concentration (Tlast) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Renal Clearance (CL) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Volume of Distribution (Vd) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Terminal Elimination Half-life (t1/2) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: Day -4 and Day -2: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Area Under the Concentration-time Curve From Time of Administration to 24 hours (AUC0-24) for Treosulfan and its Metabolite Treosulfan Monoepoxide
Time frame: At Day -4: Pre-dose, at end of infusion and at 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose
Number of Participants With Engraftment With Treosulfan-based Therapy in Moderate Renal Impairment
Time to engraftment is defined as the time between Day 0 and neutrophil/leukocyte/platelet engraftment. Engraftment includes Neutrophil engraftment, Leukocyte engraftment and Platelet engraftment. Neutrophil engraftment is defined the first of 3 consecutive days with an absolute neutrophil count (ANC) greater than (\>) 0.5\*10\^9 per liter (/L) in peripheral blood (PB) in the first of 3 consecutive days ;Leukocyte engraftment is defined as the first of 3 consecutive days with a total leukocyte count of more than 1\*10\^9/L in PB. Platelet engraftment is defined as the first of 3 consecutive days with a platelet count of at least 20\*10\^9/L or of at least 50\*10\^9/L in PB in the absence of platelet transfusion. Consecutive days is defined as 3 consecutive blood samples, if these are taken on different days.
Time frame: Day 0 to Day 28
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
A TEAE is defined as any Adverse Event (AE) that has an onset on or after the first dose of investigation medicinal product (IMP) or any pre existing condition that has worsened on or after the first dose of IMP. An SAE or serious adverse reaction (SAR) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is another medically important event.
Time frame: Day -7 to Day 28
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