Leukemia and immunedeficiency syndromes MedDRA version: 20.0 Level: SOC Classification code 10021428 Term: Immune system disorders System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.1 Level: LLT Classification code 10024329 Term: Leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Thymoglobuline
Product Name: Thymoglobuline
Pharmaceutical Form: Powder for solution for infusion
Sponsors
UMC Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients eligible for a non-haplo-identical non-T-cell depleted HCT with Thymoglobulin as part of the conditioning regimen treated in the pediatric ward of the UMCU Utrecht or the LUMC Leiden • Any stem cell source • First transplantation • Age at time of transplantation =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Ex-vivo T-cell depleted grafts • Other serotherapy in conditioning (e.g. Campath, or Campath in the bag) • Received serotherapy within 3 months before this transplantation • Pregnancy or breast-feeding or unwilling to use adequate contraceptive methods • Sensibility to rabbit proteins or previous treatment with Thymoglobulin or other rabbit ATG • Acute or chronic infections, in which each form of immune suppression is contra-indicated • Patients not planned to receive or having received at least 90% or more than 110% of the intentioned dose of Thymoglobulin • Ejection fraction < 30% or shortening fraction < 15% • No complete morphological remission (CR-status) in bone marrow in case of malignancy • History of serious immune-mediated reactions or hypersensitivity to any biological product • Participation in other trial in which the dose of Thymoglobulin is fixed to amounts other than the individualized dose.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether an individualized dosing regimen for Thymoglobulin leads to a better immune reconstitution after HCT (definition as in primary endpoint), as compared to historically non-individualized treated patients receiving Thymoglobulin as a fixed dose per kilogram body weight. The individualized dosing regimen is based on a previously treated pediatric cohort on which a population PK-PD analysis was performed. The dosing regimen was compiled using this cohort, taking into account the influence of body weight and pre-Thymoglobulin lymphocyte count and the observed variability.;Secondary Objective: not applicable;Primary end point(s): Incidence of CD4+ T-cell immune reconstitution, defined as a CD4+ T-cell count > 50 x 10e6/L in 2 consecutive measurements within 100 days.;Timepoint(s) of evaluation of this end point: 100 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Survival (overall survival, event free survival, non-relapse mortality, relapse mortality) • Relapse incidence • Incidence of viral reactivations (CMV, Adenovirus, EBV, HHV6, BK-virus) • Acute graft versus host disease (according to Glucksberg criteria) • Chronic graft versus host disease (according to Shulman criteria) • Engraftment defined as a neutrophil count > 0.5 x 109/L with use of granulocyte-colony stimulating factor (G-CSF) within 40 days • Rejection defined as >95% recipient chimerism, or reinfusion of donor cells after successful engraftment • Prospective validation of the pharmacokinetic model • Lymphocyte subset reconstitution monitored throughout the treatment (including some rare populations) for future studies;Timepoint(s) of evaluation of this end point: Within 6 months after last visit of last patient | — |
Countries
Netherlands
Contacts
Public ContactR.Admiraal, MD
UMC Utrecht
Outcome results
None listed