Study to Evaluate 13 Valent Pneumococcal Conjugate Vaccine (13vPnC) Vaccine Followed by 23-valent Pneumococcal Polysaccharide Vaccine (23vPS) Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Vaccines, Pneumococcal Conjugate Vaccine Clinical Trial

Official title:

A Phase 3, Open-label Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of 13-valent Pneumococcal Conjugate Vaccine Followed By 23-valent Pneumococcal Polysaccharide Vaccine In Recipients Of Allogeneic Hematopoietic Stem Cell Transplant Aged 2 Years And Older

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00980655
• Other study ID #: 6115A1-3003
• Secondary ID: B18510222009-012
• Status: Completed
• Phase: Phase 3
• Start date: January 18, 2010
• Est. completion date: May 16, 2013

Study information

• Verified date: November 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

People who have received an allogeneic hematopoetic stem cell transplant (HSCT) are more likely than other people to get ill from a germ called Streptococcus pneumoniae. Most people who have had a stem cell transplant are offered a vaccine called 23-valent pneumococcal polysaccharide vaccine (23vPS) to help protect against this germ. The purpose of this study is to evaluate the immune response in HSCT recipients who receive a 13 valent pneumococcal vaccine (13vPnC) followed by 23vPS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 251
• Est. completion date: May 16, 2013
• Est. primary completion date: May 16, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• Male or female subject >=2 years of age.

• Allogeneic HSCT for hematologic disorder.

• Allogeneic HSCT with full myeloablative conditioning or reduced intensity conditioning.

• Allogeneic HSCT approximately 3 to 6 months (91 days to 203 days) before enrollment.

• Stable engraftment (absolute neutrophil count (ANC) >1000/µL; platelet count >50,000/µL).

• Complete hematologic remission of underlying disease with very good partial remission (VGPR) acceptable in the case of lymphoma and myeloma.

• Subject or parent/legal guardian expected to be available for the entire study and can be contacted by telephone.

• Subject or parent/legal guardian must be able to complete an electronic diary (e-diary) and complete all relevant study procedures during study participation.

• Hematological recovery as defined by ANC >1000/µL; platelet count >50,000/µL.

• All female and male subjects who are biologically capable of having children must agree to abstinence or commit to the use of a reliable method of birth control from signing of the ICF until for 3 months after the last vaccination.

• Negative urine pregnancy test for all female subjects of child bearing potential.

Exclusion Criteria:

• Autologous HSCT.

• Receipt of donor lymphocyte infusions during the 28 days preceding enrollment.

• Uncontrolled GVHD that in the opinion of the investigator would prevent the subject from participating in the study.

• Lansky/Karnofsky Score <=60%.

• Receipt of plasma products or immunoglobulins during the 60 days preceding enrollment.

• Receipt of rituximab since HSCT.

• Receipt of chemotherapy for relapse of underlying malignant disease since HSCT.

• Human immunodeficiency virus (HIV) infection.

• Lymphoproliferative disorder since HSCT.

• Chronic illnesses with cardiac, pulmonary, renal, or liver failure that in the opinion of the investigator would prevent the subject participating in the study.

• Vaccination with any licensed or experimental pneumococcal vaccine since HSCT.

• Previous anaphylactic reaction to any vaccine or vaccine-related component.

• Bleeding diathesis or condition associated with prolonged bleeding time that would in the opinion of the investigator contraindicate intramuscular injection.

• Participation in another study with ongoing use of an unlicensed investigational product from 28 days before study enrollment until the end of the study.

• Participation in another study with ongoing use of a licensed investigational product that in the opinion of the investigator would interfere with the evaluation of the study objectives.

• Permanent residence in a nursing home or other residential care facility.

• Pregnant or breastfeeding female subject.

• Subject who is a direct relative (child, grandchild, parent, or grandparent) of study personnel, or is a member of the study personnel.

• Receipt of advanced therapy medicinal products (ATMP) including gene therapy products, somatic cell therapy products, and tissue engineered products at any time before enrollment.

• If information is available, - previous allergic or anaphylactic reaction to any vaccine or vaccine-related component in a stem cell donor.

Related Conditions & MeSH terms

• Vaccines, Pneumococcal Conjugate Vaccine

Intervention

Biological:
• 13vPnC
0.5mL 13vPnC dose will be administered intramuscularly into the left limb at visits 1,2,3 and 5. Starting 3-6 months after HSCT 3 doses given at monthly intervals. 4th dose given 6 months after 3rd dose.
• 23vPS
0.5mL dose of 23vPS will be administered intramuscularly at visit 6. 23vPS given 1 month after 4th dose of 13vPnC.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Belgium
Belgium	Algemeen Ziekenhuis St.-Jan A.V.	Brugge
Belgium	Clinical University St Luc	Brussels
Belgium	Universitaire Ziekenhuizen Leuven (UZ) Gasthuisberg	Leuven
Belgium	CHU Liege	Liege
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Czechia	Fakultni nemocnice Brno/Interni hematoonkologicka klinika	Bmo
Czechia	Fakultni nemocnice v Motole	Praha 5
France	Hôpital Jean Minjoz	Besancon
France	Hopital Henri Mondor	Créteil
France	Hôpital Henri Mondor, Pharmacie	Créteil
France	CHRU Robert Debré	Paris
France	Hôpital Saint Louis	Paris
France	Hopital Saint-Louis	PARIS Cedex 10
France	Hopital Robert Debre	Paris Cedex 19
France	Hopital Robert Debre - Service Pharmacie	PARIS Cedex 19
Germany	Charite Universitaetsmedizin	Berlin
Germany	Clinical Trial Center North MediGate GmbH	Hamburg
Germany	Klinik und Poliklinik fuer Paediatrische Haematologie und Onkologie	Hamburg
Germany	Universitaetsklinikum Hamburg Eppendorf Clinical Trial Center North MediGate GmbH	Hamburg
Germany	Universitaetsklinikum Hamburg-Eppendorf, Onkologisches Zentrum	Hamburg
Germany	Universitatsklinikum Jena	Jena
Germany	"Universitaetsklinikum Muenster,	Muenster
Germany	Universitaetsklinikum Muenster	Muenster
Netherlands	UMC Utrecht, Wilhelmina Kinder Ziekenhuis	Utrecht
Poland	Klinika Hematologii i Transplantologii	Gdansk
Poland	NZOZ "HIPOKRATES-II" Sp. z o.o.	Krakow
Poland	Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej	Wroclaw
Spain	Hospital Universitario Infantil Niño Jesús	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Sweden	Karolinska Universitetssjukhuset Huddinge	Huddinge
Sweden	Universitetssjukhuset i Lund, Barnonkologen Avd 64	Lund
Sweden	Karolinska University Hospital Huddinge	Stockholm
Sweden	Akademiska Sjukhuset, Infektionskliniken	Uppsala
United States	Texas Children's Hospital	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Columbia University Medical Center Research Pharmacy	New York	New York
United States	Columbia University Medical Center-Presbyterian Hospital Building	New York	New York
United States	Columbia University/Taub Institute Irving Center for Clinical Research	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York-Presbyterian Morgan Stanley Children's Hospital	New York	New York
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  France,  Germany,  Netherlands,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Local Reactions: 13vPnC Dose 1	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 centimeters [cm] for participants aged 2 to <12 years and 2.5 to 5.0 cm for participants aged >= 12 years); Moderate (2.5 to 7.0 cm for participants aged 2 to <12 years and 5.5 to 10.0 cm for participants aged >= 12 years); Severe (greater than [>] 7.0 cm for participants aged 2 to <12 years and >10.0 cm for participants aged >= 12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity).	Within 14 days after 13vPnC Dose 1
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Local Reactions: 13vPnC Dose 2	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 centimeters [cm] for participants aged 2 to <12 years and 2.5 to 5.0 cm for participants aged >= 12 years); Moderate (2.5 to 7.0 cm for participants aged 2 to <12 years and 5.5 to 10.0 cm for participants aged >= 12 years); Severe (greater than [>] 7.0 cm for participants aged 2 to <12 years and >10.0 cm for participants aged >= 12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity).	Within 14 days after 13vPnC Dose 2
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Local Reactions: 13vPnC Dose 3	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 centimeters [cm] for participants aged 2 to <12 years and 2.5 to 5.0 cm for participants aged >= 12 years); Moderate (2.5 to 7.0 cm for participants aged 2 to <12 years and 5.5 to 10.0 cm for participants aged >= 12 years); Severe (greater than [>] 7.0 cm for participants aged 2 to <12 years and >10.0 cm for participants aged >= 12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity).	Within 14 days after 13vPnC Dose 3
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Local Reactions: 13vPnC Dose 4	Specific local reactions were prompted for each day, and reported using an electronic diary. Redness and Swelling were scaled as Any (redness present or swelling present); Mild (0.5 to 2.0 centimeters [cm] for participants aged 2 to <12 years and 2.5 to 5.0 cm for participants aged >= 12 years); Moderate (2.5 to 7.0 cm for participants aged 2 to <12 years and 5.5 to 10.0 cm for participants aged >= 12 years); Severe (greater than [>] 7.0 cm for participants aged 2 to <12 years and >10.0 cm for participants aged >= 12 years). Pain at injection site was scaled as Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity).	Within 14 days after 13vPnC Dose 4
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Systemic Events: 13vPnC Dose 1	Specific systemic events (fever >=38 degrees Celsius [C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours).	Within 14 days after 13vPnC Dose 1
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Systemic Events: 13vPnC Dose 2	Specific systemic events (fever >=38 degrees Celsius [C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours).	Within 14 days after 13vPnC Dose 2
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Systemic Events: 13vPnC Dose 3	Specific systemic events (fever >=38 degrees Celsius [C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours).	Within 14 days after 13vPnC Dose 3
Other	Percentage of Pediatric, Adult and All Participants Reporting Pre-specified Systemic Events: 13vPnC Dose 4	Specific systemic events (fever >=38 degrees Celsius [C], fatigue, headache, vomiting, diarrhea, muscle pain, joint pain and use of medication to treat pain/fever) were prompted for each day, and reported using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any (symptom present); Mild (did not interfere with activity); Moderate (some interference with activity); Severe (prevented routine daily activity). Vomiting was scaled as: Any (vomiting present); Mild (1-2 times in 24 hours); Moderate (>2 times in 24 hours); Severe (required intravenous hydration). Diarrhea was scaled as: Any (diarrhea present); Mild (2-3 loose stools in 24 hours); Moderate (4-5 loose stools 24 hours); Severe (>=6 loose stools in 24 hours).	Within 14 days after 13vPnC Dose 4
Primary	Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 3 in All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before 13vPnC Dose 1 and after 13vPnC Dose 3 blood draws.	Before 13vPnC Dose 1 (pre-vaccination), 1 month after 13vPnC Dose 3
Secondary	Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 3 in Pediatric, Adult and All Participants	Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose 3 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.	1 month after 13vPnC Dose 3
Secondary	Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After 13vPnC Dose 4 in Pediatric, Adult and All Participants	Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) for pediatric, adult and all participants are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. Geometric means were calculated using all participants with available data for 1 month after 13vPnC Dose 4 blood draw. CI for GMC are back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.	1 month after 13vPnC Dose 4
Secondary	Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 3 in Pediatric and Adult Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 3 were computed using the logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before 13vPnC Dose 1 and after 13vPnC Dose 3 blood draws.	Before 13vPnC Dose 1 (pre-vaccination), 1 month after 13vPnC Dose 3
Secondary	Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 4 in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 4 were computed using the logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before 13vPnC Dose 1 and after 13vPnC Dose 4 blood draws.	Before 13vPnC Dose 1 (pre-vaccination), 1 month after 13vPnC Dose 4
Secondary	Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After 13vPnC Dose 3 to 1 Month After 13vPnC Dose 4 in Pediatric, Adult and All Participants	GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 3 to 1 month after 13vPnC Dose 4 were computed using the logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both after 13vPnC Dose 3 and after 13vPnC Dose 4 blood draws.	1 month after 13vPnC Dose 3, 1 month after 13vPnC Dose 4