No registrations found.
ID
Source
Brief title
Health condition
Diagnosis of severe congenital immune deficiency or of congenital hematological disorder with indication for allogeneic stem cell transplantation
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cumulative Alemtuzumab exposure (AUC) till day +7
Secondary outcome
• Immune reconstitution
• Chimerism after alloHSCT
• Incidence of acute and chronic graft-versus-host-disease and grading
• Overall survival
• Event free survival (defined as without death or retransplantation)
• Cumulative incidence of treatment-related mortality
• Cumulative incidence of graft failure (defined as non-engraftment or rejection)
• Incidence of viral primary infections or reactivations within the first 100 days
• Incidence of Donor Lymphocyte Infusion within the first 100 days
• Incidence of bacterial, parasitic and fungal primary infections within the first 100 days
• Incidence of secondary autoimmune reactions
• Incidence of secondary immune-mediated endocrine disorders
Background summary
In children, Alemtuzumab is increasingly administered off-label prior to allogeneic stem cell transplantation according to European guidelines. However, pediatric data on Alemtuzumab pharmacokinetics (PK) suggest large inter-patient variability, which significantly impacts biological efficacy and clinical outcome. Since optimal dosing of Alemtuzumab in children prior to HSCT is currently unknown, the need for further PK analyses allowing the evaluation of current clinical practice as well as possibly supporting improved patient care in this vulnerable participants group is urgent.
The aim of our observational study is to evaluate current clinical practice and develop a comprehensive population pharmacokinetic model for Alemtuzumab in children with non-malignant diseases treated with reduced intensity conditioning regimens prior to stem cell transplantation. This model will provide essential additional information on Alemtuzumab treatments and support the establishment of a rigorous therapeutic drug
monitoring.
Study objective
Primary Hypothesis
High interindividual variability of Alemtuzumab PK in children transplanted for severe non-malignant diseases crucially impacts the cumulative exposure to Alemtuzumab given intravenously as part of a reduced intensity conditioning regimen pre and post allogeneic stem cell transplantation.
Secondary Hypothesis
The exposure to Alemtuzumab correlates significantly with immune reconstitution, risk of acute and chronic GvHD and primary clinical outcome defined as incidence of infectious complications, reactive autoimmunity and secondary immune-endocrine disorders in children with non-malignant diseases undergoing alloHSCT.
Study design
Alemtuzumab levels measured during Alemtuzumab administration as well weekly till 6 weeks after allogeneic stem cell transplantation.
Inclusion criteria
• diagnosis of severe congenital immune deficiency or of congenital hematological disorder with indication for allogeneic stem cell transplantation (HSCT)
• age at diagnosis and at the time of HSCT ≤ 18 years
• Alemtuzumab treatment intravenously is given as part of a treosulfan- or a busulfan-based reduced intensity conditioning regimen prior to HSCT
• all donor types and hematopoietic stem cell sources will be considered
• HSCT is performed in a study participating center
• written consent of the parents (legal guardian) and of the patient herself or himself if ≥14 years old (≥12 years old in the Netherlands)
• in case of multiple HSCT per patient, further transplantations will only be considered if a minimal serotherapy-free interval of 3 months is preceding the second transplant
Exclusion criteria
• patients who do not fulfill the inclusion criteria
• patients with known hypersensitivity to Alemtuzumab
• patients treated with other serotherapy drugs (e.g. anti-thymocyte globulin – ATG) within the same conditioning regimen prior to HSCT
• patients who received any other serotherapy in the last 3 months before starting this observational study
• known HIV-positivity
• active malignancy
• pregnancy/lactation
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8185 |
| CCMO | NL68506.058.19 |
| OMON | NL-OMON55607 |