Genetic Disorder, Malignancy, Metabolic Disease
Conditions
Keywords
allogeneic hematopoietic stem cell transplantation, pharmacokinetics, pediatrics
Brief summary
This study will describe the pharmacokinetic disposition of biologically active rabbit anti-thymocyte globulin (rATG) after a consistent dose of 7.5 mg/kg/course given as part of the conditioning regimen in children undergoing hematopoeitic stem cell transplantation (HSCT).
Detailed description
Allogeneic hematopoeitic stem cell transplantation (HSCT) is a therapeutic option for patients with malignancies as well as metabolic and genetic diseases. Conditioning regimens given prior to donor cell infusion aim to ablate the recipient bone-marrow, to allow engraftment of the stem-cells infused, and to prevent acute versus host disease (aGVHD). Anti-thymocyte globulin (ATG) is one of the immunosuppressive drugs given as a preparative regimen for HSCT. Subjects will be given an ATG infusion daily for 3 days prior to HSCT and serum levels will be collected, as per schedule, with the last sample taken +100 days post-HSCT.
Interventions
BIOLOGICALThymoglobulin (rATG)
Thymoglobulin 2.5 mg/kg of body weight IV administered daily for 3 days prior to HSCT. Thymoglobulin infused over a minimum of 6 hours for the first infusion and over at least 4 to 6 hours on subsequent days of therapy.
Sponsors
The Hospital for Sick Children
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* All patients who are scheduled to receive ATG 2.5mg/kg/day for 3 days as part of the preparative regimen for HSCT, as determined by the responsible HSCT physician. * Written, informed consent
Exclusion criteria
* Hypersensitivity to rabbit proteins or to any product excipients * Active acute or chronic infections, which would contraindicate any additional immunosuppression * Known pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Disposition of ATG After a 7.5 mg/kg/Course | 100 days | ATG pharmacokinetic parameters were estimated using a noncompartmental model. Maximum Observed Concentration (Cmax) of ATG After a 7.5 mg/kg/Course was measured |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thymoglobulin Thymoglobulin 7.5 mg/kg/course prior to HSCT
Thymoglobulin (rATG): Thymoglobulin 2.5 mg/kg of body weight IV administered daily for 3 days prior to HSCT.
Thymoglobulin infused over a minimum of 6 hours for the first infusion and over at least 4 to 6 hours on subsequent days of therapy. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Thymoglobulin |
|---|---|
| Age, Categorical <=18 years | 17 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Pharmacokinetic Disposition of ATG After a 7.5 mg/kg/Course
ATG pharmacokinetic parameters were estimated using a noncompartmental model. Maximum Observed Concentration (Cmax) of ATG After a 7.5 mg/kg/Course was measured
Time frame: 100 days
Population: Blood samples for ATG concentration determination were obtained at 0, +1, +4, +7, +14, +28, +60, +75 and +100 days post-HSCT. ATG serum concentrations were analyzed using a validated immunoassay. ATG pharmacokinetic parameters were estimated using a noncompartmental model. The relationship between HSCT outcomes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Thymoglobulin | Pharmacokinetic Disposition of ATG After a 7.5 mg/kg/Course | 7.86 mg/L | Standard Deviation 2.9 |