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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00886496
• Other study ID #: CDR0000523819
• Secondary ID: ENZON-EZN-2232-0
• Status: Withdrawn
• Phase: Phase 1
• First received: April 21, 2009
• Last updated: June 19, 2012
• Start date: November 2006
• Est. completion date: April 2011

Study information

• Verified date: August 2007
• Source: Enzon Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 17 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

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

Intervention

Biological:
• recombinant human mannose-binding lectin

Locations

Country	Name	City	State
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Enzon Pharmaceuticals, Inc.	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity
Primary	Pharmacokinetics
Primary	Efficacy