A Multi-Center Study of the Safety, Tolerability, Pharmacokinetics and Dose Escalation of Intravenous Recombinant Human Mannose-Binding-Lectin (rhMBL) in MBL Deficient Pediatric Hematology/Oncology Patients With Fever and Neutropenia
- Determine the safety and tolerability of recombinant human mannose-binding lectin (MBL)
in pediatric patients with MBL deficiency and fever and neutropenia who are undergoing
cytotoxic chemotherapy for hematological/oncological disease.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the pharmacodynamic effect of this drug in these patients.
- Determine nonspecific activation of complement by in vivo determination of C3d
complement activation in patients treated with this drug.
- Determine the ex-vivo activity of recombinant MBL in opsonization capacity of patients'
sera to yeast and bacteria.
- Determine immunogenicity of this drug in these patients.
- Determine the incidence and duration of fever and breakthrough infections in patients
treated with this drug.
OUTLINE: This is a non-randomized, multicenter, open-label, prospective, cohort study.
Patients are assigned to 1 of 2 treatment groups.
- Group I: Patients receive low-dose recombinant human mannose-binding lectin (MBL) IV
over 1 hour within 72 hours of onset of fever and neutropenia.
- Group II: Patients receive high-dose recombinant human MBL IV over 1 hour within 72
hours of onset of fever and neutropenia.
Patients undergo blood collection periodically during study for pharmacokinetic,
pharmacodynamic, MBL immunogenicity, and opsonization/phagocytosis studies.
After completion of study treatment, patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Supportive Care
Thomas J. Walsh, MD
National Cancer Institute (NCI)
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|