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NCT Number: NCT00112112

Safety Study to Evaluate FluMist in Immunocompromised Children

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.

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Key information

Conditions

Cancer Infections Influenza, Human Neoplasms Orthomyxoviridae Infections RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

5 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Rochester School of Medicine & Dentistry, Rochester, New York, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

FluMist

Biological

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

Biological

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).

Primary outcomes

  1. Number of Participants Who Had Reactogenicity Events (REs)

    Time frame: 0-42 days after study vaccination

    Reactogenicity events (REs) are predefined solicited adverse events (AEs) that can potentially occur after vaccine administration. The REs for this study included fever, runny nose/nasal congestion, sore throat, cough, vomiting, headache, muscle aches, chills, tiredness, and irritability.

  2. Number of Participants Who Had Serious Adverse Events (SAEs)

    Time frame: 0-180 days after study vaccination

    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.

  3. Number of Participants Who Had Adverse Events (AEs)

    Time frame: 0-42 days after study vaccination

    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.

  4. Number of Significant New Medical Conditions (SNMCs)

    Time frame: 43-180 days after study vaccination

    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.

Secondary outcomes

  1. Number of Participants Shedding Vaccine-like Virus

    Time frame: 3-5 days after study vaccination

    Number of participants with nasal swab samples that contained vaccine-like virus are reported.

  2. Number of Participants Shedding Vaccine-like Virus

    Time frame: 7-10 days after study vaccination

    Number of participants with nasal swab samples that contained vaccine-like virus are reported.

  3. Number of Participants Shedding Vaccine-like Virus

    Time frame: 14-28 days after study vaccination

    Number of participants with nasal swab samples that contained vaccine-like virus are reported.

  4. Number of Participants Shedding Vaccine-like Virus

    Time frame: 35-42 days after study vaccination

    Number of participants with nasal swab samples that contained vaccine-like virus are reported. Sample was collected at this time point only if health assessment indicated presence of a respiratory illness, including otitis media.

  5. Number of Participants Shedding Vaccine-like Virus

    Time frame: Unscheduled visits occurring during 0-42 days after study vaccination

    Number of participants with nasal swab samples that contained vaccine-like virus are reported.

  6. T- and B-lymphocyte Subsets by Flow Cytometry - Cluster of Differentiation (CD) 19

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of CD19 lymphocyte subsets as a percentage of total lymphocytes.

  7. T- and B-lymphocyte Subsets by Flow Cytometry - CD3

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of CD3 lymphocyte subsets as a percentage of total lymphocytes.

  8. T- and B-lymphocyte Subsets by Flow Cytometry - CD4

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of CD4 lymphocyte subsets as a percentage of total lymphocytes.

  9. T- and B-lymphocyte Subsets by Flow Cytometry - CD8

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of CD8 lymphocyte subsets as a percentage of total lymphocytes.

  10. T- and B-lymphocyte Subsets by Flow Cytometry - CD19

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of CD19 lymphocyte subsets as a percentage of total lymphocytes.

  11. T- and B-lymphocyte Subsets by Flow Cytometry - CD3

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of CD3 lymphocyte subsets as a percentage of total lymphocytes.

  12. T- and B-lymphocyte Subsets by Flow Cytometry - CD4

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of CD4 lymphocyte subsets as a percentage of total lymphocytes.

  13. T- and B-lymphocyte Subsets by Flow Cytometry - CD8

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of CD8 lymphocyte subsets as a percentage of total lymphocytes.

  14. Interferon (INF)-Gamma

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation spots-forming cells per 10^5 T cells is reported.

  15. INF-Gamma

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation spots-forming cells per 10^5 T cells is reported.

  16. INF-Gamma

    Time frame: 35-42 days after study vaccination

    Mean and standard deviation spots-forming cells per 10^5 T cells is reported.

  17. Interleukin (IL)-4

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation spots-forming cells per 10^5 T cells is reported.

  18. IL-4

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation spots-forming cells per 10^5 T cells is reported.

  19. IL-4

    Time frame: 35-42 days after study vaccination

    Mean and standard deviation spots-forming cells per 10^5 T cells is reported.

  20. Human Leukocyte Antigen (HLA) Matched Tetramers CD8+

    Time frame: pre-dosing (Day 0)

    The antigen-specific response of the T cell populations was measured using HLA-matched tetramers specific for human CD8 cell populations.

  21. HLA Matched Tetramers CD8+

    Time frame: 7-10 days after study vaccination

    The antigen-specific response of the T cell populations was measured using HLA-matched tetramers specific for human CD8 cell populations.

  22. HLA Matched Tetramers CD8+

    Time frame: 35-42 days after study vaccination

    The antigen-specific response of the T cell populations was measured using HLA-matched tetramers specific for human CD8 cell populations.

  23. Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza A/H1N1 Hemagglutination Inhibition (HAI) Titers From Baseline to Day 35-42

    Time frame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination

    Participants with a geometric mean fold-rise in influenza-specific nasal HAI titers >= 4 from baseline are reported.

  24. Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza A/H3N2 HAI Titers From Baseline to Day 35-42

    Time frame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination

    Participants with a geometric mean fold-rise in influenza-specific nasal HAI titers >= 4 from baseline are reported.

  25. Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza B HAI Titers From Baseline to Day 35-42

    Time frame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination

    Participants with a geometric mean fold-rise in influenza-specific nasal HAI titers >= 4 from baseline are reported.

  26. Number of Participants Who Experienced a >= 4-fold Rise in Influenza A/H1N1 Microneutralization Titers From Baseline to Day 35-42

    Time frame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination

    Participants with a geometric mean fold-rise in influenza-specific nasal microneutralization titers >= 4 from baseline are reported.

  27. Number of Participants Who Experienced a >= 4-fold Rise in Influenza A/H3N2 Microneutralization Titers From Baseline to Day 35-42

    Time frame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination

    Participants with a geometric mean fold-rise in influenza-specific nasal microneutralization titers >= 4 from baseline are reported.

  28. Number of Participants Who Experienced a >= 4-fold Rise in Influenza B Microneutralization Titers From Baseline to Day 35-42

    Time frame: Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination

    Participants with a geometric mean fold-rise in influenza-specific nasal microneutralization titers >= 4 from baseline are reported.

  29. Influenza A/H1N1 Immunoglobulin A (IgA)

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  30. Influenza A/H1N1 IgA

    Time frame: 3-5 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  31. Influenza A/H1N1 IgA

    Time frame: 7-10 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  32. Influenza A/H1N1 IgA

    Time frame: 14-28 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  33. Influenza A/H1N1 IgA

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  34. Influenza A/H3N2 IgA

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  35. Influenza A/H3N2 IgA

    Time frame: 3-5 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  36. Influenza A/H3N2 IgA

    Time frame: 7-10 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  37. Influenza A/H3N2 IgA

    Time frame: 14-28 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  38. Influenza A/H3N2 IgA

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  39. Influenza B IgA

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  40. Influenza B IgA

    Time frame: 3-5 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  41. Influenza B IgA

    Time frame: 7-10 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  42. Influenza B IgA

    Time frame: 14-28 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  43. Influenza B IgA

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgA from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  44. T- and B-lymphocyte Subsets by Flow Cytometry - CD56

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of CD56 lymphocyte subsets is reported.

  45. T- and B-lymphocyte Subsets by Flow Cytometry - CD56

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of CD56 lymphocyte subsets is reported.

  46. T- and B-lymphocyte Subsets by Flow Cytometry - White Blood Cells

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of white blood cells subsets is reported.

  47. T- and B-lymphocyte Subsets by Flow Cytometry - White Blood Cells

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of white blood cells subsets is reported.

  48. T- and B-lymphocyte Subsets by Flow Cytometry - Lymphocytes

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of lymphocytes subsets is reported.

  49. T- and B-lymphocyte Subsets by Flow Cytometry - Lymphocytes

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of lymphocytes subsets is reported.

  50. T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Lymphocytes

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of absolute lymphocytes subsets is reported.

  51. T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Lymphocytes

    Time frame: 7-10 days after study vaccination

    Mean and standard deviation results of absolute lymphocytes subsets is reported.

  52. T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Neutrophils

    Time frame: pre-dosing (Day 0)

    Mean and standard deviation results of absolute neutrophils subsets is reported.

  53. Influenza A/H1N1 Immunoglobulin G (IgG)

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgG from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  54. Influenza A/H1N1 IgG

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgG from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  55. Influenza A/H3N2 IgG

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgG from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  56. Influenza A/H3N2 IgG

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgG from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  57. Influenza B IgG

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgG from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  58. Influenza B IgG

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgG from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  59. Influenza A/H1N1 Immunoglobulin M (IgM)

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgM from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  60. Influenza A/H1N1 IgM

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgM from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  61. Influenza A/H3N2 IgM

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgM from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  62. Influenza A/H3N2 IgM

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgM from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  63. Influenza B IgM

    Time frame: pre-dosing (Day 0)

    Mean of influenza-specific IgM from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

  64. Influenza B IgM

    Time frame: 35-42 days after study vaccination

    Mean of influenza-specific IgM from nasal swab is reported. Titers of < 1 were assigned the value of 0.5.

Sponsors and collaborators

Lead sponsor

MedImmune LLC

Industry

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
May 30, 2005
Registry last updated
Aug 14, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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