Standard vs High-Dose Trivalent Inactivated Flu Vaccine in Adult Hematopoetic Stem Cell Transplant (HSCT) Recipients

• Sponsor: Vanderbilt-Ingram Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01215734
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

Hypothesis 1: The safety profile in adult allogeneic stem cell hematopoietic transplant (SCT) recipients after high dose (HD) trivalent inactivated influenza vaccine (TIV) will not be significantly different from adult stem cell transplant recipients receiving standard dose (SD) TIV.

• Specific Aim 1: To compare safety profile of high dose trivalent inactivated influenza vaccine to standard dose trivalent inactivated influenza vaccine in adult hematopoietic stem cell transplant recipients.

Hypothesis 2: Adult stem cell transplant recipients who received the higher dose trivalent influenza vaccine will have a greater frequency of (at least a 4-fold) rise in antibody titers to influenza antigens compared to those who receive standard dose trivalent influenza vaccine.

• Specific Aim 2: To compare humoral immune responses of adult hematopoietic stem cell transplant recipients influenza virus antigens included in trivalent influenza vaccine after high dose or standard dose trivalent influenza vaccine.

Condition or Disease	Intervention/Treatment	Phase
Adult Stem Cell Hematopoetic Transplant	Biological: High-Dose Trivalent Inactivated Influenza Vaccine (HD-TIV); Biological: Standard Dose Trivalent Inactivated Flu Vaccine	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Randomized Double-Blind, Comparison of Standard Dose Trivalent Inactivated Influenza Vaccine Versus High-Dose Trivalent Inactivated Influenza Vaccine in Adult Stem Cell Hematopoetic Transplant Recipients
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: High-Dose Trivalent Inactivated Influenza Vaccine Forty adult hematopoetic stem cell transplant recipients at least 6 months post transplant will receive high dose trivalent influenza vaccine	Biological: High-Dose Trivalent Inactivated Influenza Vaccine (HD-TIV); 0.5 ml of HD-TIV on visit 1
Active Comparator: Standard dose Trivalent Inactivated Flu Vaccine Twenty Adult stem cell transplant recipients at least 6 months post transplant will receive standard dose trivalent influenza vaccine.	Biological: Standard Dose Trivalent Inactivated Flu Vaccine; Twenty adult hematopoetic stem cell transplant recipients will receive 0.5 ml standard dose trivalent influenza vaccine on visit 1.

Outcome Measures

Primary Outcome Measures

1. Patients Experiencing at Least 1 Solicited Local and/or Systemic Adverse Event After High Dose (HD) Trivalent Influenza Vaccine (TIV) or Standard Dose (SD) Trivalent Influenza Vaccine in Adult Hematopoetic Stem Cell Transplant (SCT) Recipients [Day of TIV to 7 days after TIV]

   Patients were questioned about the following adverse events related to TIV: Local: pain, tenderness, swelling/induration, or erythema at injection site. Systemic: fatigue/malaise, headache, nausea, vomiting, body ache not at injection site, fever >= 100.4 degrees Fahrenheit, or change in activity level.

Secondary Outcome Measures

1. Patients Receiving HD or SD TIV With a 4-fold Rise in Hemagglutination Inhibition (HAI) Titers Relative to Baseline for Each of 3 Influenza Viruses [Before TIV and 28-42 days after TIV]

   Adult hematopoetic stem cell transplant recipients at least 6 months post-transplant receiving either HD or SD TIV who had blood drawn at pre-vaccination and at 28-42 days post-vaccination and who experienced a 4-fold rise in each of three post-vaccination influenza antibody titers, relative to their baseline titers. Trivalent vaccine is for the H1N1/H3N2/B influenzas. A 4-fold rise in type-specific antibody titer is considered adequate antibody response to the specific influenza virus

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Allogeneic hematopoietic stem cell transplant recipients who are >6 post-transplant

• greater than or equal to 18 years of age

• Available for duration of study

• If patients are on immunosuppressive therapy for treatment of graft versus host disease (GVHD): only those on stable doses for at least 4 weeks or on tapering doses will be eligible.

Exclusion Criteria:

• History of hypersensitivity to previous influenza vaccination or hypersensitivity to eggs/egg protein

• History of Guillain-Barre syndrome

• Evidence of hematologic malignancy or disease relapse post-transplant (mixed chimerisms and molecular evidence of disease is permitted)

• Non-allogeneic (e.g. autologous) hematopoietic SCT recipients

• History of receiving 2011 - 2012 influenza vaccine

• History of proven influenza disease after September 1, 2011.

• Pregnant females

• Have any condition that would, in the opinion of the site investigator, place them at an unacceptable risk of injury or render them unable to meet the requirements of the protocol

• Have any condition that the investigator believes may interfere with successful completion of the study

• Platelet count less than 50,000 cells/μL

• History of known infection with HIV, Hepatitis B or Hepatitis C

• History of known latex hypersensitivity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt-Ingram Cancer Center, Clinical Trials Information Program	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt-Ingram Cancer Center

Investigators

• Principal Investigator: Natasha Halasa, M.D., M.P.H., Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Publications

None provided.

• Responsible Party: Natasha Halasa, MD, Assistant Professor of Pediatrics, Pediatric Infectious Diseases, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT01215734
• Other Study ID Numbers: VICC BMT 1057; 100980; 100980
• First Posted: Oct 6, 2010
• Last Update Posted: Mar 8, 2013
• Last Verified: Feb 1, 2013

• Additional relevant MeSH terms: Vaccines

Study Results

Participant Flow

Recruitment Details	This phase X, double-blind study was conducted from September 2011 - April 2012.
Pre-assignment Detail	Forty-seven patients consented to participate in this study, three were determined ineligible.

Arm/Group Title	High-Dose Trivalent Inactivated Influenza Vaccine	Standard Dose Trivalent Inactivated Flu Vaccine
Arm/Group Description	Forty adult hematopoetic stem cell transplant recipients at least 6 months post-transplant will receive high dose trivalent influenza vaccine High-Dose Trivalent Inactivated Influenza Vaccine (HD-TIV) : 0.5 ml of HD-TIV on visit 1	Twenty Adult stem cell transplant recipients at least 6 months post-transplant will receive standard dose trivalent influenza vaccine. Standard Dose Trivalent Inactivated Flu Vaccine : Twenty adult hematopoetic stem cell transplant recipients will receive 0.5 ml standard dose trivalent influenza vaccine on visit 1.
Period Title: Overall Study
STARTED	29	15
COMPLETED	29	14
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	High-Dose Trivalent Inactivated Influenza Vaccine	Standard Dose Trivalent Inactivated Flu Vaccine	Total
Arm/Group Description	Forty adult hematopoetic stem cell transplant recipients at least 6 months post-transplant will receive high dose trivalent influenza vaccine High-Dose Trivalent Inactivated Influenza Vaccine (HD-TIV) : 0.5 ml of HD-TIV on visit 1	Twenty Adult stem cell transplant recipients at least 6 months post-transplant will receive standard dose trivalent influenza vaccine. Standard Dose Trivalent Inactivated Flu Vaccine : Twenty adult hematopoetic stem cell transplant recipients will receive 0.5 ml standard dose trivalent influenza vaccine on visit 1.	Total of all reporting groups
Overall Participants	29	15	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	27 93.1%	14 93.3%	41 93.2%
>=65 years	2 6.9%	1 6.7%	3 6.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (12)	49 (14)	50 (12)
Sex: Female, Male (Count of Participants)
Female	11 37.9%	5 33.3%	16 36.4%
Male	18 62.1%	10 66.7%	28 63.6%
Region of Enrollment (participants) [Number]
United States	29 100%	15 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Patients Experiencing at Least 1 Solicited Local and/or Systemic Adverse Event After High Dose (HD) Trivalent Influenza Vaccine (TIV) or Standard Dose (SD) Trivalent Influenza Vaccine in Adult Hematopoetic Stem Cell Transplant (SCT) Recipients
Description	Patients were questioned about the following adverse events related to TIV: Local: pain, tenderness, swelling/induration, or erythema at injection site. Systemic: fatigue/malaise, headache, nausea, vomiting, body ache not at injection site, fever >= 100.4 degrees Fahrenheit, or change in activity level.
Time Frame	Day of TIV to 7 days after TIV

Outcome Measure Data

Analysis Population Description

Patients who received either the high-dose TIV or the standard dose TIV

Arm/Group Title	High-Dose Trivalent Inactivated Influenza Vaccine	Standard Dose Trivalent Inactivated Flu Vaccine
Arm/Group Description	High Dose: Adult hematopoetic stem cell transplant recipients at least 6 months post transplant will receive HD TIV (60 micrograms [µg] per antigen) on visit 1	Standard Dose TIV : Adult hematopoetic stem cell transplant recipients at least 6 months post-transplant will receive SD (15 µg/per antigen) TIV on visit 1.
Measure Participants	29	15
Local Adverse Events	18 62.1%	4 26.7%
Systemic Adverse Events	14 48.3%	7 46.7%

2. Secondary Outcome

Title	Patients Receiving HD or SD TIV With a 4-fold Rise in Hemagglutination Inhibition (HAI) Titers Relative to Baseline for Each of 3 Influenza Viruses
Description	Adult hematopoetic stem cell transplant recipients at least 6 months post-transplant receiving either HD or SD TIV who had blood drawn at pre-vaccination and at 28-42 days post-vaccination and who experienced a 4-fold rise in each of three post-vaccination influenza antibody titers, relative to their baseline titers. Trivalent vaccine is for the H1N1/H3N2/B influenzas. A 4-fold rise in type-specific antibody titer is considered adequate antibody response to the specific influenza virus
Time Frame	Before TIV and 28-42 days after TIV

Outcome Measure Data

Analysis Population Description

Patients who received either the high-dose or the standard dose TIV and who had blood drawn for HAI titers before TIV and at 28-42 days after TIV. Data not available for 5 HD and 1 SD patients.

Arm/Group Title	High-Dose Trivalent Inactivated Influenza Vaccine	Standard Dose Trivalent Inactivated Flu Vaccine
Arm/Group Description	High Dose: Adult hematopoetic stem cell transplant recipients at least 6 months post transplant will receive HD TIV (60 micrograms [µg] per antigen) on visit 1	Standard Dose TIV : Adult hematopoetic stem cell transplant recipients at least 6 months post-transplant will receive SD (15 µg/per antigen) TIV on visit 1.
Measure Participants	24	14
H1N1 Influenza	12 41.4%	5 33.3%
H3N2 Influenza	10 34.5%	5 33.3%
B Influenza	10 34.5%	6 40%

Adverse Events

Arm/Group Title	High-Dose Trivalent Inactivated Influenza Vaccine		Standard Dose Trivalent Inactivated Flu Vaccine
Arm/Group Description	Forty adult hematopoetic stem cell transplant recipients at least 6 months post transplant will receive high dose trivalent influenza vaccine High-Dose Trivalent Inactivated Influenza Vaccine (HD-TIV) : 0.5 ml of HD-TIV on visit 1		Twenty Adult stem cell transplant recipients at least 6 months post transplant will receive standard dose trivalent influenza vaccine. Standard Dose Trivalent Inactivated Flu Vaccine : Twenty adult hematopoetic stem cell transplant recipients will receive 0.5 ml standard dose trivalent influenza vaccine on visit 1.
All Cause Mortality
	High-Dose Trivalent Inactivated Influenza Vaccine		Standard Dose Trivalent Inactivated Flu Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	High-Dose Trivalent Inactivated Influenza Vaccine		Standard Dose Trivalent Inactivated Flu Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/29 (37.9%)		7/15 (46.7%)
Blood and lymphatic system disorders
Anemia	0/29 (0%)	0	1/15 (6.7%)	1
febrile neutropenia	0/29 (0%)	0	1/15 (6.7%)	1
Cardiac disorders
chest pain, cardiac	0/29 (0%)	0	1/15 (6.7%)	2
heart failure	1/29 (3.4%)	1	0/15 (0%)	0
palpitations	0/29 (0%)	0	1/15 (6.7%)	1
pericardial effusion	1/29 (3.4%)	2	1/15 (6.7%)	1
Supraventricular tachycardia	1/29 (3.4%)	1	0/15 (0%)	0
Gastrointestinal disorders
abdominal pain	1/29 (3.4%)	1	0/15 (0%)	0
diarrhea	1/29 (3.4%)	1	0/15 (0%)	0
nausea	2/29 (6.9%)	2	2/15 (13.3%)	2
vomiting	1/29 (3.4%)	1	1/15 (6.7%)	1
rectal abscess	1/29 (3.4%)	1	0/15 (0%)	0
General disorders
fever	1/29 (3.4%)	1	1/15 (6.7%)	1
malaise	1/29 (3.4%)	1	0/15 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/29 (3.4%)	1	0/15 (0%)	0
Infections and infestations
Infections and infestations other	0/29 (0%)	0	1/15 (6.7%)	1
Laryngitis	0/29 (0%)	0	1/15 (6.7%)	1
Methicillin-resistant Staphylococcus aureus bacteremia	0/29 (0%)	0	1/15 (6.7%)	1
Investigations
Alkaline phosphatase increased	0/29 (0%)	0	1/15 (6.7%)	1
Creatinine increased	0/29 (0%)	0	1/15 (6.7%)	1
Platelet count decreased	0/29 (0%)	0	1/15 (6.7%)	1
weight loss	1/29 (3.4%)	1	0/15 (0%)	0
Metabolism and nutrition disorders
dehydration	0/29 (0%)	0	1/15 (6.7%)	1
Hyperglycemia	0/29 (0%)	0	1/15 (6.7%)	1
Hyperkalemia	1/29 (3.4%)	1	0/15 (0%)	0
Hypoalbuminemia	0/29 (0%)	0	1/15 (6.7%)	1
Hypomagnesemia	0/29 (0%)	0	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Planned knee replacement surgery	1/29 (3.4%)	1	0/15 (0%)	0
diffuse muscle pain	1/29 (3.4%)	1	0/15 (0%)	0
Nervous system disorders
Chronic inflammatory demyelinating polyneuropathy	1/29 (3.4%)	1	0/15 (0%)	0
Presyncope	1/29 (3.4%)	1	0/15 (0%)	0
Transient ischemic attacks	1/29 (3.4%)	1	0/15 (0%)	0
Renal and urinary disorders
Acute kidney injury	2/29 (6.9%)	2	2/15 (13.3%)	2
Respiratory, thoracic and mediastinal disorders
upper respiratory infection	1/29 (3.4%)	1	1/15 (6.7%)	1
cough	1/29 (3.4%)	1	0/15 (0%)	0
dyspnea	1/29 (3.4%)	1	2/15 (13.3%)	3
hypoxia	1/29 (3.4%)	1	0/15 (0%)	0
pleural effusion	0/29 (0%)	0	1/15 (6.7%)	1
respiratory failure	0/29 (0%)	0	1/15 (6.7%)	1
bonchitis obliterans	0/29 (0%)	0	1/15 (6.7%)	1
wheezing	0/29 (0%)	0	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme	1/29 (3.4%)	1	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	High-Dose Trivalent Inactivated Influenza Vaccine		Standard Dose Trivalent Inactivated Flu Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)		5/15 (33.3%)
Gastrointestinal disorders
anorexia	2/29 (6.9%)	2	0/15 (0%)	0
mucositits oral	0/29 (0%)	0	1/15 (6.7%)	1
vomiting	0/29 (0%)	0	1/15 (6.7%)	1
General disorders
edema limbs	0/29 (0%)	0	1/15 (6.7%)	1
Hepatobiliary disorders
hepatobiliary disorders, other	0/29 (0%)	0	1/15 (6.7%)	1
Investigations
investigations, other	2/29 (6.9%)	2	1/15 (6.7%)	1
Metabolism and nutrition disorders
hypokalemia	0/29 (0%)	0	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
upper respiratory infection	3/29 (10.3%)	3	1/15 (6.7%)	1
cough	1/29 (3.4%)	1	2/15 (13.3%)	2
nasal congestion	0/29 (0%)	0	1/15 (6.7%)	1
wheezing	0/29 (0%)	0	1/15 (6.7%)	1
Skin and subcutaneous tissue disorders
dry skin	0/29 (0%)	0	1/15 (6.7%)	1
skin and other subcutaneous disorders-other	0/29 (0%)	0	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.