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

June 19, 2012 updated by: Enzon Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: NON_RANDOMIZED
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Pharmacokinetics
Efficacy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Enzon Pharmaceuticals, Inc.

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Study Completion (ACTUAL)

April 1, 2011

Study Registration Dates

First Submitted

April 21, 2009

First Submitted That Met QC Criteria

April 21, 2009

First Posted (ESTIMATE)

April 23, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 20, 2012

Last Update Submitted That Met QC Criteria

June 19, 2012

Last Verified

August 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000523819
  • ENZON-EZN-2232-03
  • NCI-07-C-0027

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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