Safety Study to Evaluate FluMist in Immunocompromised Children

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112112
• Other study ID #: MI-CP114
• Status: Completed
• Phase: Phase 1
• First received: May 27, 2005
• Last updated: July 31, 2012
• Start date: August 2005
• Est. completion date: May 2008

Study information

• Verified date: July 2012
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 17 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cancer

Intervention

Biological:
• FluMist
The total volume of 0.5 mL was administered intranasally with a spray applicator (approximately 0.25 mL into each nostril). Each dose contained approximately 10 to 7th TCID 50 (median tissue culture infectious dose) of each of three influenza virus strains. During the 2005 enrollment period, the three 2004/2005 influenza virus strains were used: A/New Caledonia/20/99(H1N1), A/Wyoming/03/2003(H3N2), and B/Jilin/20/2003). During the 2006 and 2007 enrollment periods, the three 2005/2006 influenza virus strains were used: A/New Caledonia/20/99(H1N1), A/California/7/2004(H3N2), and B/Jiangsu/10/2003 (B/Shanghai/361/2002-like. brief description of the arm. This element may not be necessary if the associated intervention descriptions contain sufficient information to describe the arm.
• Placebo
Placebo intranasal mist was composed of allantoic fluid stabilized with buffer containing sucrose, potassium phosphate, and monosodium glutamate. The total volume of 0.5 mL was administered intranasally with a spray applicator (approximately 0.25 mL into each nostril).

Locations

Country	Name	City	State
United States	St. Jude's Children's Research Hospital	Memphis	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	University of Rochester School of Medicine & Dentistry	Rochester	New York
United States	Children's Hospital Regional Medical Center	Seattle	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Had Reactogenicity Events (REs)	Reactogenicity events (REs) are predefined solicited adverse events (AEs) that can potentially occur after vaccine administration. For the participants enrolled in this study REs include fever, runny nose/nasal congestion, sore throat, cough, vomiting, headache, muscle aches, chills, tiredness, and irritability.	0-42 days after study vaccination	Yes
Primary	Number of Serious Adverse Events (SAEs)	An SAE is any AE that results in any of the following outcomes: •Death • Life-threatening • Inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant disability or incapacity • Congenital anomaly/birth defect (in the offspring of a study participant) • An important medical event that may may jeopardize the study participant and may require medical or surgical intervention to prevent one of the outcomes listed above.	0-180 days after study vaccination	Yes
Primary	Number of Participants Who Had Adverse Events (AEs)	An AE is any untoward medical occurrence in a patient or clinical investigations study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	0-42 days after study vaccination	Yes
Primary	Number of Significant New Medical Conditions (SNMCs)	A significant new medical condition is defined as a new diagnosis of a chronic medical condition that does not meet the criteria of a SAE.	43-180 days after study vaccination	Yes
Secondary	Number of Participants Shedding Vaccine-like Virus	Number of participants with nasal swab samples that contained vaccine-like virus.	3-5 days after study vaccination	No
Secondary	Number of Participants Shedding Vaccine-like Virus	Number of participants with nasal swab samples that contained vaccine-like virus.	7-10 days after study vaccination	No
Secondary	Number of Participants Shedding Vaccine-like Virus	Number of participants with nasal swab samples that contained vaccine-like virus.	14-28 days after study vaccination	No
Secondary	Number of Participants Shedding Vaccine-like Virus	Number of participants with nasal swab samples that contained vaccine-like virus. Sample was collected at this time point only if health assessment indicated presence of a respiratory illness, including otitis media.	35-42 days after study vaccination	No
Secondary	Number of Participants Shedding Vaccine-like Virus	Number of participants with nasal swab samples that contained vaccine-like virus.	Unscheduled visits occurring during days 0-42 days after study vaccination	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD19	Mean and standard deviation results of CD19 lymphocyte subsets as a percentage of total lymphocytes.	pre-dosing (Day 0)	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD3	Mean and standard deviation results of CD3 lymphocyte subsets as a percentage of total lymphocytes.	pre-dosing (Day 0)	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD4	Mean and standard deviation results of CD4 lymphocyte subsets as a percentage of total lymphocytes.	pre-dosing (Day 0)	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD8	Mean and standard deviation results of CD8 lymphocyte subsets as a percentage of total lymphocytes.	pre-dosing (Day 0)	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD19	Mean and standard deviation results of CD19 lymphocyte subsets as a percentage of total lymphocytes.	Day 7-10	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD3	Mean and standard deviation results of CD3 lymphocyte subsets as a percentage of total lymphocytes.	Day 7-10	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD4	Mean and standard deviation results of CD4 lymphocyte subsets as a percentage of total lymphocytes.	Day 7-10	No
Secondary	T- and B-lymphocyte Subsets by Flow Cytometry - CD8	Mean and standard deviation results of CD8 lymphocyte subsets as a percentage of total lymphocytes.	Day 7-10	No
Secondary	Interferon (INF)-Gamma	Mean and standard deviation spots-forming cells per 10^5 T cells	pre-dosing (Day 0)	No
Secondary	INF-Gamma	Mean and standard deviation spots-forming cells per 10^5 T cells	Day 7-10	No
Secondary	INF-Gamma	Mean and standard deviation spots-forming cells per 10^5 T cells	Day 35-42	No
Secondary	Interleukin (IL)-4	Mean and standard deviation spots-forming cells per 10^5 T cells	pre-dosing (Day 0)	No
Secondary	IL-4	Mean and standard deviation spots-forming cells per 10^5 T cells	Day 7-10	No
Secondary	IL-4	Mean and standard deviation spots-forming cells per 10^5 T cells	Day 35-42	No
Secondary	Human Leukocyte Antigen (HLA) Matched Tetramers CD8+		pre-dosing (Day 0)	No
Secondary	HLA Matched Tetramers CD8+		Day 7-10	No
Secondary	HLA Matched Tetramers CD8+		Day 35-42	No
Secondary	Number of Participants Who Experienced a = 4-fold Rise in Serum Influenza A/H1N1 Hemagglutination Inhibition (HAI) Titers	Participants with a geometric mean fold-rise in influenza-specific nasal HAI titers = 4 from baseline	Baseline to Day 35-42	No
Secondary	Number of Participants Who Experienced a = 4-fold Rise in Serum Influenza A/H3N2 HAI Titers	Participants with a geometric mean fold-rise in influenza-specific nasal HAI titers = 4 from baseline	Baseline to Day 35-42	No
Secondary	Number of Participants Who Experienced a = 4-fold Rise in Serum Influenza B HAI Titers	Participants with a geometric mean fold-rise in influenza-specific nasal HAI titers = 4 from baseline	Baseline to Day 35-42	No
Secondary	Number of Participants Who Experienced a = 4-fold Rise in Influenza A/H1N1 Microneutralization Titers	Participants with a geometric mean fold-rise in influenza-specific nasal microneutralization titers = 4 from baseline	Baseline to Day 35-42	No
Secondary	Number of Participants Who Experienced a = 4-fold Rise in Influenza A/H3N2 Microneutralization Titers	Participants with a geometric mean fold-rise in influenza-specific nasal microneutralization titers = 4 from baseline	Baseline to Day 35-42	No
Secondary	Number of Participants Who Experienced a = 4-fold Rise in Influenza B Microneutralization Titers	Participants with a geometric mean fold-rise in influenza-specific nasal microneutralization titers = 4 from baseline	Baseline to Day 35-42	No
Secondary	Influenza A/H1N1 Immunoglobulin A (IgA)	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	pre-dosing (Day 0)	No
Secondary	Influenza A/H1N1 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 3-5	No
Secondary	Influenza A/H1N1 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 7-10	No
Secondary	Influenza A/H1N1 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 14-28	No
Secondary	Influenza A/H1N1 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 35-42	No
Secondary	Influenza A/H3N2 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	pre-dosing (Day 0)	No
Secondary	Influenza A/H3N2 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 3-5	No
Secondary	Influenza A/H3N2 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 7-10	No
Secondary	Influenza A/H3N2 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 14-28	No
Secondary	Influenza A/H3N2 IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 35-42	No
Secondary	Influenza B IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	pre-dosing (Day 0)	No
Secondary	Influenza B IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 3-5	No
Secondary	Influenza B IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 7-10	No
Secondary	Influenza B IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 14-28	No
Secondary	Influenza B IgA	Mean of influenza-specific IgA from nasal swab. Titers of < 1 were assigned the value of 0.5.	Day 35-42	No

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