Clinical trial NCT00112112: Safety Study to Evaluate FluMist in Immunocompromised Children
Official title: A Phase I Randomized, Double-Blind Trial of the Safety and Immunogenicity of FluMist® A Live, Intranasal Influenza Virus Vaccine vs. Placebo in Immunocompromised Children Ages 5 Through 17 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: cancer, pediatric, influenza, vaccine
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2005-05-30
Enrollment: 20
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main purpose of this study is to get information about the safety of a flu vaccine spray, called FluMist, in children with cancer. The study is also being done to find out how much and how long the vaccine spray can be found in the nose.

Detailed description: This study is a randomized, double-blind Phase 1 study of FluMist vs. placebo in mild to moderately immunocompromised children 5 to 17 years of age with cancer. The primary objective of this study is to describe the safety of FluMist compared with placebo in mild to moderately immunocompromised children with cancer. The secondary objectives of this study are to describe the immune responses following vaccination with FluMist and to determine the incidence and duration of viral replication following vaccination with FluMist.

The standard 0.5 mL dose of vaccine or placebo was administered intranasally. Patients were evaluated at four visits scheduled between days 3-5, days 7-10, days 14-28, and days 35-42 for viral shedding via nasal swabs. Safety outcomes were collected at study clinic visits or by telephone contact through 42 days post dose. Serious adverse events and significant new medical conditions were collected through 180 days after receipt of investigational product.

Immune responses were measured by detection of influenza-specific antibodies as measured by the standard hemagglutination inhibition (HAI) assay. Influenza-specific serum antibody isotype levels were determined and nasal swab specimens were analyzed for the expression of influenza-specific immunoglobulin A (IgA). Serum was analyzed for its ability to neutralize viral particles from infecting Madin-Darby canine kidney cells (microneutralization). Baseline immunosuppression as measured by expression of T- and B-lymphocyte subsets was compared to immunosuppression at time points after vaccination. The duration of viral replication and the titers of live-attenuated influenza virus shed was evaluated from nasal swab specimens collected at scheduled time points after administration of FluMist.

Eligibility criteria: Inclusion Criteria:

* Age 5 through 17 years of age (not yet reached their 18th birthday) at the time of entry into the study;
* Patient's parent or legal guardian available by telephone during the course of the study;
* Written informed consent (assent if applicable) and Health Insurance Portability and Accountability Act (HIPAA) authorization (if applicable) obtained from the patient's parent or legal guardian;
* Ability of the patient or patient's parent/guardian to comply with the requirements of the protocol;
* Currently receiving chemotherapy and/or radiation therapy for the treatment of cancer or have received chemotherapy in the past 12 weeks;
* If the subject's underlying cancer is a solid tumor, current status must be stable disease, partial response, or complete response to therapy; if the subject's underlying disease is a hematologic malignancy, current status must be in remission;
* Estimated life expectancy of \>1 year; and
* Currently has no worse than mild to moderate immunosuppression (meets none of the exclusion criteria).

Exclusion Criteria:

* History of hypersensitivity to any component of FluMist, including egg or egg products, or monosodium glutamate;
* History of hypersensitivity to gentamicin;
* Close contact with a severely immunocompromised patient (e.g., a hematopoietic stem cell transplant patient, during those periods in which the immunocompromised patient requires care in a protective environment);
* History of Guillain-Barré syndrome;
* History of asthma;
* Use of aspirin or salicylate-containing products in the 30 days prior to study vaccination or expected receipt within the study duration;
* Use of anti-influenza medications (including amantadine, rimantadine, oseltamivir, and zanamivir) within 14 days prior to enrollment or expected receipt (unless medically indicated) during this study;
* Currently receiving inhaled steroid therapy;
* Receipt of immunoglobulin within the past 90 days;
* Receipt of stem cell transplant;
* Acute febrile \[\>100.0°F (37.8°C) oral\] illness or acute respiratory illness, e.g., cough or sore throat, within three days prior to enrollment;
* Administration of any live vaccine within 30 days prior to enrollment or if receipt of another live vaccine is expected within 30 days after the vaccination in this study;
* Administration of any inactivated vaccine within two weeks prior to enrollment or if receipt of another inactivated vaccine is expected within two weeks after the vaccination in this study;
* Receipt of an investigational product studied under an investigational new drug (IND) within 10 days prior to study entry or expected receipt of such an investigational product within 10 days after study vaccination (Note: an investigational product not studied under an IND is allowed at the investigator's discretion);
* Pregnancy or, in biologically capable females (e.g., menses within the last year), not willing to agree to acceptable birth control for three months after study vaccination (for those biologically capable, a urine pregnancy test must be performed on the day of vaccination with a negative result);
* Female who is breastfeeding or lactating;
* Any condition or receipt of other medication that, in the opinion of the investigator, might interfere with the evaluation of the vaccine or interpretation of study results;
* At the study screening visit (within 16 days before study vaccination) a CD4+ T cell percentage of \<15%;
* At study entry, an absolute neutrophil count less than or equal to 500 cells/mm3;
* Receipt of high-dose systemic corticosteroids (≥ 2 mg/kg total of prednisone or equivalent given daily or on alternating days) for ≥ 14 consecutive days within 30 days prior to or following study vaccination

Primary outcomes:
measure: Number of Participants Who Had Reactogenicity Events (REs)
timeFrame: 0-42 days after study vaccination
measure: Number of Participants Who Had Serious Adverse Events (SAEs)
timeFrame: 0-180 days after study vaccination
measure: Number of Participants Who Had Adverse Events (AEs)
timeFrame: 0-42 days after study vaccination
measure: Number of Significant New Medical Conditions (SNMCs)
timeFrame: 43-180 days after study vaccination
Secondary outcomes:
measure: Number of Participants Shedding Vaccine-like Virus
timeFrame: 3-5 days after study vaccination
measure: Number of Participants Shedding Vaccine-like Virus
timeFrame: 7-10 days after study vaccination
measure: Number of Participants Shedding Vaccine-like Virus
timeFrame: 14-28 days after study vaccination
measure: Number of Participants Shedding Vaccine-like Virus
timeFrame: 35-42 days after study vaccination
measure: Number of Participants Shedding Vaccine-like Virus
timeFrame: Unscheduled visits occurring during 0-42 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - Cluster of Differentiation (CD) 19
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD3
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD4
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD8
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD19
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD3
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD4
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD8
timeFrame: 7-10 days after study vaccination
measure: Interferon (INF)-Gamma
timeFrame: pre-dosing (Day 0)
measure: INF-Gamma
timeFrame: 7-10 days after study vaccination
measure: INF-Gamma
timeFrame: 35-42 days after study vaccination
measure: Interleukin (IL)-4
timeFrame: pre-dosing (Day 0)
measure: IL-4
timeFrame: 7-10 days after study vaccination
measure: IL-4
timeFrame: 35-42 days after study vaccination
measure: Human Leukocyte Antigen (HLA) Matched Tetramers CD8+
timeFrame: pre-dosing (Day 0)
measure: HLA Matched Tetramers CD8+
timeFrame: 7-10 days after study vaccination
measure: HLA Matched Tetramers CD8+
timeFrame: 35-42 days after study vaccination
measure: Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza A/H1N1 Hemagglutination Inhibition (HAI) Titers From Baseline to Day 35-42
timeFrame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination
measure: Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza A/H3N2 HAI Titers From Baseline to Day 35-42
timeFrame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination
measure: Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza B HAI Titers From Baseline to Day 35-42
timeFrame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination
measure: Number of Participants Who Experienced a >= 4-fold Rise in Influenza A/H1N1 Microneutralization Titers From Baseline to Day 35-42
timeFrame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination
measure: Number of Participants Who Experienced a >= 4-fold Rise in Influenza A/H3N2 Microneutralization Titers From Baseline to Day 35-42
timeFrame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination
measure: Number of Participants Who Experienced a >= 4-fold Rise in Influenza B Microneutralization Titers From Baseline to Day 35-42
timeFrame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination
measure: Influenza A/H1N1 Immunoglobulin A (IgA)
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H1N1 IgA
timeFrame: 3-5 days after study vaccination
measure: Influenza A/H1N1 IgA
timeFrame: 7-10 days after study vaccination
measure: Influenza A/H1N1 IgA
timeFrame: 14-28 days after study vaccination
measure: Influenza A/H1N1 IgA
timeFrame: 35-42 days after study vaccination
measure: Influenza A/H3N2 IgA
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H3N2 IgA
timeFrame: 3-5 days after study vaccination
measure: Influenza A/H3N2 IgA
timeFrame: 7-10 days after study vaccination
measure: Influenza A/H3N2 IgA
timeFrame: 14-28 days after study vaccination
measure: Influenza A/H3N2 IgA
timeFrame: 35-42 days after study vaccination
measure: Influenza B IgA
timeFrame: pre-dosing (Day 0)
measure: Influenza B IgA
timeFrame: 3-5 days after study vaccination
measure: Influenza B IgA
timeFrame: 7-10 days after study vaccination
measure: Influenza B IgA
timeFrame: 14-28 days after study vaccination
measure: Influenza B IgA
timeFrame: 35-42 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD56
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - CD56
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - White Blood Cells
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - White Blood Cells
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - Lymphocytes
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - Lymphocytes
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Lymphocytes
timeFrame: pre-dosing (Day 0)
measure: T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Lymphocytes
timeFrame: 7-10 days after study vaccination
measure: T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Neutrophils
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H1N1 Immunoglobulin G (IgG)
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H1N1 IgG
timeFrame: 35-42 days after study vaccination
measure: Influenza A/H3N2 IgG
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H3N2 IgG
timeFrame: 35-42 days after study vaccination
measure: Influenza B IgG
timeFrame: pre-dosing (Day 0)
measure: Influenza B IgG
timeFrame: 35-42 days after study vaccination
measure: Influenza A/H1N1 Immunoglobulin M (IgM)
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H1N1 IgM
timeFrame: 35-42 days after study vaccination
measure: Influenza A/H3N2 IgM
timeFrame: pre-dosing (Day 0)
measure: Influenza A/H3N2 IgM
timeFrame: 35-42 days after study vaccination
measure: Influenza B IgM
timeFrame: pre-dosing (Day 0)
measure: Influenza B IgM
timeFrame: 35-42 days after study vaccination
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester School of Medicine & Dentistry
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Memphis
country: United States
facility: St. Jude's Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Seattle
country: United States
facility: Children's Hospital Regional Medical Center
state: Washington
Study officials:
affiliation: MedImmune LLC
name: Raburn Mallory, MD
role: STUDY_DIRECTOR
References:
citation: Halasa N, Englund JA, Nachman S, Weinberg GA, Huber VC, Allison K, Dubovsky F, Yi T, McCullers JA, Flynn PM. Safety of live attenuated influenza vaccine in mild to moderately immunocompromised children with cancer. Vaccine. 2011 May 31;29(24):4110-5. doi: 10.1016/j.vaccine.2011.03.097. Epub 2011 Apr 13.