Recombinant Human Mannose-Binding Lectin (MBL) in Treating Young Patients With MBL Deficiency and Fever and Neutropenia

RATIONALE: Recombinant human mannose-binding lectin (MBL) may be effective in preventing infection in young patients with fever and neutropenia receiving chemotherapy for blood disease or cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of recombinant human mannose-binding lectin in treating young patients with MBL deficiency and fever and neutropenia.

OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Undergoing cytologic chemotherapy for hematological/oncological disease
* Must meet all of the following criteria:

  * Documented mannose-binding lectin (MBL) levels \< 300 ng/mm³ within the past week
  * Fever (oral temperature \> 100.4° F)
  * Neutropenia, defined as absolute neutrophil count ≤ 1,000/mm³ with the anticipation that the counts will fall below 500/mm\^3
  * Receiving broad spectrum antibiotic therapy for fever and neutropenia

PATIENT CHARACTERISTICS:

* No serious illness, in the opinion of the principal investigator, that would preclude study compliance
* No known allergic reactions to mannose-binding lectin or other human plasma products
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier method contraception during and for ≥ 30 days after completion of study treatment
* AST and ALT ≤ 5 times upper limit of normal (ULN)
* Bilirubin ≤ 2.5 times ULN
* Creatinine clearance \> 60 mL/min OR creatinine based on age as follows:

  * No more than 0.8 mg/dL (for patients 5 years of age and under)
  * No more than 1.0 mg/dL (for patients 6-9 years of age)
  * No more than 1.2 mg/dL (for patients 10-12 years of age)
  * No more than 1.4 mg/dL (for patients over 13 years of age \[female\])
  * No more than 1.5 mg/dL (for patients 13-15 years of age \[male\])
  * No more than 1.7 mg/dL (for patients of 16 years of age \[male\])
* No poor venous access that would preclude IV drug delivery or multiple blood draws
* Patients on hemodialysis must be able to tolerate IV fluid on non-dialysis days

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 30 days since prior investigational agents

  * Investigational use of an FDA-approved drug allowed
* No concurrent preparative regimen for a bone marrow or hematopoietic stem cell transplantation
* No concurrent participation in another clinical trial with an investigational agent