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

NCT ID: NCT00886496

Last Updated: 2012-06-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2011-04-30

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.

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Interventions

recombinant human mannose-binding lectin

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Enzon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Principal Investigators

Thomas J. Walsh, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Children's Hospital of Orange County

Orange, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

ENZON-EZN-2232-03

Identifier Type: -

Identifier Source: secondary_id

NCI-07-C-0027

Identifier Type: -

Identifier Source: secondary_id

CDR0000523819

Identifier Type: -

Identifier Source: org_study_id