Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Synteract, Inc. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treosulfan and Fludarabine | Experimental | Participants will receive treosulfan 10 gram per square meter (g/m^2), intravenous (IV) infusion, given over 2 hours once daily on three consecutive days (day -4 to day -2), followed by fludarabine, 30 milligram per square meter (mg/m^2) IV infusion once daily on 5 consecutive days (days -6 to -2), preceding allogeneic haematopoietic stem cell transplantation (alloHSCT) on Day 0. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treosulfan | Drug | IV infusion |
| |
| Fludarabine |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From Time of Administration to the Last Measurable Concentration (AUClast) for Treosulfan | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for Treosulfan and its Metabolite Treosulfan Monoepoxide | 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Participants considered not eligible for alloHSCT, for instance due to severe concomitant illness, within 3 weeks before the scheduled Baseline Visit:
Have a known coronary artery disease, history of myocardial infarction, cardiac dysfunction, including cardiomyopathies, heart failure (New York Heart Association Class II and above), and cardiac arrhythmias (including paroxysmal and permanent atrial fibrillation), interventricular conduction delay and / or bundle branch block (QRS duration >120 milliseconds [ms]).
Have Fredericia-corrected QTc (QTcF) interval >450 ms in men and >470 ms in women.
Have active malignant involvement of the central nervous system.
Are human immunodeficiency virus (HIV) positive or have an active non controlled infectious disease under treatment including fungal infection, active viral liver infection, or known severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) viral infection at the time of enrolment.
Have previously had more than one alloHSCT.
Have pleural effusion or ascites of >1.0 liters (L).
Are pregnant or breast-feeding.
Have uncontrolled or severe intercurrent medical condition.
Have known hypersensitivity to treosulfan, fludarabine, and / or related ingredients, Fanconi anaemia and other disorders resulting from DNA repair disorders.
Are participating in another experimental drug trial (except those for coronavirus disease [COVID 19] vaccines) within 4 weeks prior to the Day 7 Baseline Visit. This exception serves to comply with subject's interests as this population is at a high risk of COVID 19 complications, if the disease occurs. COVID 19 vaccination details (including vaccine name, batch and manufacturer, dose, date of administration, and whether the right or left arm was injected) should be captured as a concomitant medication to enable better assessment of the overall effect of COVID 19 vaccination on oncology trial results.
Exhibit non cooperative behaviour or non compliance.
Have psychiatric diseases or conditions that might compromise the ability to give informed consent.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ute Eckenbach | SyntheractHCR | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois | Chicago | Illinois | 60612 | United States | ||
| The Ohio State University |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
IV infusion |
|
| 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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. | 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. | Day -7 to Day 28 |
| Columbus |
| Ohio |
| 43210 |
| United States |
| VCU Massey Cancer Center | Richmond | Virginia | 23298 | United States |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C018404 | treosulfan |
| C024352 | fludarabine |
Not provided
Not provided
Not provided