MBL-Deficient, Neutropenia
Conditions
Keywords
MBL-deficient, chemotherapy, neutropenia, chemotherapy-induced neutropenia
Brief summary
The pharmacokinetics, and clinical and biological effects of MBL replacement therapy in MBL-deficient children during chemotherapy-induced neutropenia were studied.
Detailed description
Mannan Binding Lectin (MBL) is a member of the lectin pathway of the complement system and plays an important role in the innate immune system. MBL replacement in MBL-deficient children with chemotherapy-induced neutropenia represents a new approach to lower the risk of febrile episodes, of hospital admission, of prolonged use of intravenous antibiotics and of severe infections. The aim of the Phase II study is to find evidence for the correct prediction of plasma levels of MBL necessary for clinical effects and biological efficacy, to confirm the dosage regimen needed to reach the required MBL plasma levels, and reconfirm the safety and lack of side-effects.
Interventions
DRUGMannan Binding Lectin (MBL)
DRUGMannan Binding Lectin
MBL dose at a twice weekly dose interval (3 or 4 days): 0.2 mg/kg, for a 3-day interval; 0.3 mg/kg, for a 4-day interval
Sponsors
Landsteiner Foundation for Blood Transfusion
Prothya Biosolutions
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
Inclusion criteria
* Children ages 0 - 12 years, during chemotherapy, and expected to become neutropenic * MBL deficiency by genotype or phenotype (\< 100 ng/ml) * Informed consent and assent of patient and/or legal representative
Exclusion criteria
* Inability or unwillingness to comply with the protocol or likely inability to complete the study period * Known allergic reactions to MBL and other human plasma products * Participation in other investigational drug studies within the last month * Clinically relevant abnormalities in: serum immunoglobulins IgG, IgA, IgM; blood counts; complement factors measured by AP50, CH50; urine protein and cell counts; serum creatinine and liver enzymes, as routinely determined for regular patient care.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| pharmacokinetics of MBL | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
Secondary
| Measure | Time frame |
|---|---|
| days of hospital admission | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
| number and type of infections | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
| days of fever | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
| MBL-dependent opsonizing capacity in vitro | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
| safety and incidence of side effects | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
| use of antibiotics or antifungal medication | until the patient's absolute neutrophil count (ANC) is above 500/uL blood. |
Countries
Netherlands
Outcome results
None listed