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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


Phase 1
2 Years
17 Years
Not Enrolling
Both
Fever, Sweats, and Hot Flashes, Infection, Leukemia, Lymphoma, Myelodysplastic Syndromes, Neutropenia, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Toxicity

Principal Investigator

Thomas J. Walsh, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000523819

NCT ID:

NCT00886496

Start Date:

November 2006

Completion Date:

April 2011

Related Keywords:

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

Name

Location

Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970