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
2 Years
17 Years
Both
Fever, Sweats, and Hot Flashes, Infection, Leukemia, Lymphoma, Myelodysplastic Syndromes, Neutropenia, Unspecified Childhood Solid Tumor, Protocol Specific
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 Philadelphia | Philadelphia, Pennsylvania 19104 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
