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

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

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.

Study Overview

• Status: Completed
• Conditions: Vaccines, Pneumococcal Conjugate Vaccine
• Intervention / Treatment: Biological: 13vPnC; Biological: 23vPS

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Belgium, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Brugge, Belgium, 8000
    • Algemeen Ziekenhuis St.-Jan A.V.
  • Brussels, Belgium, 1200
    • Clinical University St Luc
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven (UZ) Gasthuisberg
  • Liege, Belgium, 4000
    • CHU Liege
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont
• Czechia
  • Bmo, Czechia, 625 00
    • Fakultni nemocnice Brno/Interni hematoonkologicka klinika
  • Praha 5, Czechia, 15006
    • Fakultni nemocnice v Motole
• France
  • Besancon, France, 25000
    • Hopital Jean Minjoz
  • Créteil, France, 94000
    • Hôpital Henri Mondor
  • Créteil, France, 94010
    • Hôpital Henri Mondor, Pharmacie
  • PARIS Cedex 10, France, 75475
    • Hôpital Saint-Louis
  • PARIS Cedex 19, France, 75935
    • Hopital Robert Debre - Service Pharmacie
  • Paris, France, 75010
    • Hôpital Saint louis
  • Paris, France, 75019
    • CHRU Robert Debré
  • Paris Cedex 19, France, 75019
    • Hôpital Robert Debré
• Germany
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin
  • Hamburg, Germany, 20246
    • Clinical Trial Center North MediGate GmbH
  • Hamburg, Germany, 20246
    • Klinik und Poliklinik fuer Paediatrische Haematologie und Onkologie
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg Eppendorf Clinical Trial Center North MediGate GmbH
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf, Onkologisches Zentrum
  • Jena, Germany, 07740
    • Universitätsklinikum Jena
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Muenster, Germany, 48149
    • "Universitaetsklinikum Muenster,
• Netherlands
  • Utrecht, Netherlands, 3584 EA
    • UMC Utrecht, Wilhelmina Kinder Ziekenhuis
• Poland
  • Gdansk, Poland, 80-952
    • Klinika Hematologii i Transplantologii
  • Krakow, Poland, 31-223
    • NZOZ "HIPOKRATES-II" Sp. z o.o.
  • Wroclaw, Poland, 50-345
    • Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej
• Spain
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28009
    • Hospital Universitario Infantil Niño Jesus
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
• Sweden
  • Goteborg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset
  • Huddinge, Sweden, 141 86
    • Karolinska Universitetssjukhuset Huddinge
  • Lund, Sweden, 221 85
    • Universitetssjukhuset i Lund, Barnonkologen Avd 64
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital Huddinge
  • Uppsala, Sweden, 751 85
    • Akademiska Sjukhuset, Infektionskliniken
• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • New York
    • New Hyde Park, New York, United States, 11040
      • Steven and Alexandra Cohen Children's Medical Center of New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center Research Pharmacy
    • New York, New York, United States, 10032
      • Columbia University Medical Center-Presbyterian Hospital Building
    • New York, New York, United States, 10032
      • Columbia University/Taub Institute Irving Center for Clinical Research
    • New York, New York, United States, 10032
      • New York-Presbyterian Morgan Stanley Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	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.; Biological: 23vPS; 0.5mL dose of 23vPS will be administered intramuscularly at visit 6. 23vPS given 1 month after 4th dose of 13vPnC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Cordonnier C, Ljungman P, Juergens C, Maertens J, Selleslag D, Sundaraiyer V, Giardina PC, Clarke K, Gruber WC, Scott DA, Schmoele-Thoma B; 3003 Study Group. Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged >/=2 years: an open-label study. Clin Infect Dis. 2015 Aug 1;61(3):313-23. doi: 10.1093/cid/civ287. Epub 2015 Apr 13.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2010
• Primary Completion (Actual): May 16, 2013
• Study Completion (Actual): May 16, 2013

Study Registration Dates

• First Submitted: September 18, 2009
• First Submitted That Met QC Criteria: September 18, 2009
• First Posted (Estimate): September 21, 2009

Study Record Updates

• Last Update Posted (Actual): December 20, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 6115A1-3003; B1851022 (Other Identifier: Alias Study Number); 2009-012087-13 (EudraCT Number)