Clinical trial NCT00886496: Recombinant Human Mannose-Binding Lectin (MBL) in Treating Young Patients With MBL Deficiency and Fever and Neutropenia
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Fever, Sweats, and Hot Flashes
Infection
Leukemia
Lymphoma
Myelodysplastic Syndromes
Neutropenia
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: Enzon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-04-23
Enrollment: 0
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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

Primary outcomes:
measure: Toxicity
measure: Pharmacokinetics
measure: Efficacy
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: National Cancer Institute (NCI)
name: Thomas J. Walsh, MD
role: PRINCIPAL_INVESTIGATOR
References: