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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Fever, Sweats, and Hot Flashes, Infection, Leukemia, Lymphoma, Myelodysplastic Syndromes, Neutropenia, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: recombinant human mannose-binding lectin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant human mannose-binding lectin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  |  | 
| Pharmacokinetics |  |  | 
| Efficacy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified childhood solid tumor, protocol specific, fever, sweats, and hot flashes, neutropenia, infection, recurrent childhood small noncleaved cell lymphoma, stage I and II childhood small noncleaved cell lymphoma, stage I childhood small noncleaved cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage III and IV childhood small noncleaved cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood small noncleaved cell lymphoma, recurrent childhood lymphoblastic lymphoma, stage I and II childhood lymphoblastic lymphoma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III and IV childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, childhood Burkitt lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage II childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, childhood acute lymphoblastic leukemia in remission, recurrent childhood acute lymphoblastic leukemia, untreated childhood acute lymphoblastic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, untreated childhood acute myeloid leukemia and other myeloid malignancies, childhood grade III lymphomatoid granulomatosis, childhood nasal type extranodal NK/T-cell lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood large cell lymphoma, stage I childhood large cell lymphoma, stage II childhood large cell lymphoma, stage III and IV childhood large cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood large cell lymphoma