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

Sponsor

Enzon Pharmaceuticals, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT00886496

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Fever, Sweats, and Hot Flashes Infection Leukemia Lymphoma Myelodysplastic Syndromes Neutropenia Unspecified Childhood Solid Tumor, Protocol Specific	Biological: recombinant human mannose-binding lectin	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Study Start Date :

Nov 1, 2006

Actual Study Completion Date :

Apr 1, 2011

Outcome Measures

Primary Outcome Measures

Toxicity []
Pharmacokinetics []
Efficacy []

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Orange County	Orange	California	United States	92868
2	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104