A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)

NCT ID: NCT03565900

Last Updated: 2023-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 277 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-12
• Study Completion Date: 2021-11-04

Brief Summary

The purpose of this study is to 1) evaluate the safety and tolerability, and immunogenicity of blinded V114 and Prevnar 13™ within each vaccination group, and 2) evaluate the safety and tolerability, and immunogenicity of PNEUMOVAX™23 (administered as open label, 12 months after allogeneic hematopoietic stem cell transplant [allo-HSCT] in participants who do not develop chronic graft-versus-host disease [GVHD]).

Conditions

Pneumococcal Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

V114

Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1, Day 30 and Day 60 and a single 0.5 mL IM injection of PNEUMOVAX™23 at 12 months after HSCT. Participants will have received HSCT 90 to 180 days prior to Day 1. Those who develop chronic graft-versus-host-disease (GVHD) during the first year after HSCT will receive V114 instead of PNEUMOVAX™23 as their fourth dose.

Group Type: EXPERIMENTAL

V114

Intervention Type: BIOLOGICAL

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose.

PNEUMOVAX™23

Intervention Type: BIOLOGICAL

23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose

Prevnar 13™

Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1, Day 30 and Day 60 and a single 0.5 mL IM injection of PNEUMOVAX™23 at 12 months after HSCT. Participants will have received HSCT 90 to 180 days prior to Day 1. Those who develop chronic GVHD during the first year after HSCT will receive Prevnar 13™ instead of PNEUMOVAX™23 as their fourth dose.

Group Type: ACTIVE_COMPARATOR

Prevnar 13™

Intervention Type: BIOLOGICAL

13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg), and aluminum phosphate adjuvant (125 mcg aluminum) in each 0.5 ml dose

PNEUMOVAX™23

Intervention Type: BIOLOGICAL

23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose

Interventions

V114

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose.

Intervention Type: BIOLOGICAL

Prevnar 13™

13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg), and aluminum phosphate adjuvant (125 mcg aluminum) in each 0.5 ml dose

Intervention Type: BIOLOGICAL

PNEUMOVAX™23

23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose

Intervention Type: BIOLOGICAL

Other Intervention Names

VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine

Eligibility Criteria

Inclusion Criteria

• Received a human leukocyte antigen (HLA) compatible donor including haploidentical and mismatched (related or unrelated) first allogeneic HSCT (i.e., bone marrow or peripheral blood stem cell) 90 to 180 days prior to randomization.
• Received the allogeneic HSCT for acute lymphoblastic leukemia (ALL) in first or second remission, acute myeloid leukemia (AML) in first or second remission, chronic myeloid leukemia (CML) in first chronic or accelerated phase, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myelofibrosis and myeloproliferative diseases, and non-malignant disease such as aplastic anemia or sickle cell disease in participants ≥18 years of age and any non-malignant disease for participants 3 to <18 years of age.
• Life expectancy >12 months after allogeneic HSCT, according to investigator judgement.
• Clinically stable engraftment according to investigator judgment.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a) not a woman of childbearing potential (WOCBP) OR b) a WOCBP who agrees to use acceptable contraceptive methods during the treatment period and for at least 6 weeks after the last dose of study intervention.

Exclusion Criteria

• Receipt of a previous allogeneic HSCT.
• Received allogeneic HSCT with ex-vivo graft manipulation, in vivo T cell depletion with alemtuzumab, or haploidentical allogeneic HSCT with high dose anti-thymocyte globulin.
• Received allogeneic HSCT for multiple myeloma or, for participants ≥18 years of age only, for any nonmalignant diseases except sickle cell disease and aplastic anemia.
• Persistent or relapsed primary disease after allogeneic HSCT.
• History of severe GVHD (Grade 3 or 4 GVHD) after allogeneic HSCT.
• Planned organ transplantation after allogeneic HSCT.
• History of culture-positive pneumococcal disease occurring after allogeneic HSCT.
• Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine.
• History of acquired immunodeficiency such as documented HIV infection, or anatomic asplenia.
• Coagulation disorder contraindicating intramuscular vaccinations.
• Severe hepatic impairment (defined as Child-Pugh Class C) at Screening.
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) >6 × upper limit of normal (ULN) or serum total bilirubin >2.5 × ULN at Screening.
• A WOCBP who has a positive urine or serum pregnancy test before the 1st vaccination.
• Received chimeric antigen receptor T-cell (CAR-T) therapy or checkpoint inhibitor directed therapy (i.e., anti-Programmed Cell Death (PD)-1) after allogeneic HSCT.
• Received or planned to receive anti-Cluster of Differentiation (CD) 20 B-cell targeted therapy (e.g., rituximab) after allogeneic HSCT.
• Non-study pneumococcal vaccine administered after allogeneic HSCT, or is expected to receive non-study pneumococcal vaccine during participation in the study.
• Is currently participating or has participated in an interventional clinical study with an investigational compound/agent or device within 2 weeks of participating in this current study, or plans to receive any investigational compound/agent or device (in addition to existing therapy) within 2 weeks of any vaccination, that in the opinion of the investigator would interfere with the evaluation of the study objectives.
• Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence as assessed by the study investigator.
• Has history or current evidence of any condition, therapy, laboratory test result abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study.
• Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study.

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Stanford Health Care ( Site 0005)

Palo Alto, California, United States

Children's Hospital Colorado ( Site 0166)

Aurora, Colorado, United States

University of Florida ( Site 0011)

Gainesville, Florida, United States

University of Chicago ( Site 0016)

Chicago, Illinois, United States

Indiana Blood and Marrow Transplantation ( Site 0001)

Indianapolis, Indiana, United States

University of Kansas Medical Center ( Site 0007)

Kansas City, Kansas, United States

Johns Hopkins - University ( Site 0023)

Baltimore, Maryland, United States

Children's Mercy Hospital ( Site 0167)

Kansas City, Missouri, United States

Montefiore Einstein Center ( Site 0164)

The Bronx, New York, United States

Cincinnati Children's Hospital Medical Center ( Site 0010)

Cincinnati, Ohio, United States

Cleveland Clinic Foundation ( Site 0168)

Cleveland, Ohio, United States

Oregon Health & Science University ( Site 0018)

Portland, Oregon, United States

Baylor College of Medicine - Texas Children's Hospital ( Site 0165)

Houston, Texas, United States

St. Vincent's Hospital ( Site 0041)

Sydney, New South Wales, Australia

The Children s Hospital at Westmead ( Site 0191)

Westmead, New South Wales, Australia

Royal Adelaide Hospital ( Site 0040)

Adelaide, South Australia, Australia

Austin Health-Austin Hospital ( Site 0038)

Heidelberg, Victoria, Australia

The Alfred Hospital ( Site 0037)

Melbourne, Victoria, Australia

Royal Melbourne Hospital ( Site 0039)

Parkville, Victoria, Australia

Cliniques Universitaires Saint-Luc ( Site 0122)

Brussels, Bruxelles-Capitale, Region de, Belgium

UZ Leuven ( Site 0119)

Leuven, Vlaams-Brabant, Belgium

AZ Sint Jan Brugge-Oostende ( Site 0118)

Bruges, West-Vlaanderen, Belgium

AZ Delta ( Site 0120)

Roeselare, West-Vlaanderen, Belgium

Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0121)

Liège, , Belgium

Hospital Sao Rafael ( Site 0049)

Salvador, Estado de Bahia, Brazil

Santa Casa de Misericordia de Belo Horizonte ( Site 0050)

Belo Horizonte, Minas Gerais, Brazil

Instituto de Cancer e Transplante de Curitiba ICTR ( Site 0051)

Curitiba, Paraná, Brazil

Nova Scotia Health Authority QEII-HSC ( Site 0033)

Halifax, Nova Scotia, Canada

Juravinski Cancer Centre ( Site 0032)

Hamilton, Ontario, Canada

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0031)

Montreal, Quebec, Canada

Hospital Pablo Tobon Uribe ( Site 0077)

Medellín, Antioquia, Colombia

Fundacion Valle del Lili ( Site 0073)

Cali, Valle del Cauca Department, Colombia

Centro Medico Imbanaco de Cali S.A ( Site 0075)

Cali, Valle del Cauca Department, Colombia

CHU de Nice ( Site 0084)

Nice, Alpes-Maritimes, France

Hopital Jean Minjoz Besancon ( Site 0085)

Besançon, Doubs, France

CHU de Grenoble Hopital Nord ( Site 0083)

La Tronche, Isere, France

CHRU de Lille - Hopital Claude Huriez ( Site 0090)

Lille, Nord, France

CHU Henri Mondor ( Site 0081)

Créteil, Val-de-Marne, France

Hopital Saint-Antoine ( Site 0089)

Paris, , France

Universitaetsklinikum Koeln ( Site 0105)

Cologne, North Rhine-Westphalia, Germany

Universitaetsklinikum Duesseldorf ( Site 0107)

Düsseldorf, North Rhine-Westphalia, Germany

Universitaetsmedizin Mainz ( Site 0106)

Mainz, Rhineland-Palatinate, Germany

Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0187)

Monterrey, Nuevo León, Mexico

Servicio de hematologia Universidad Autonoma de Nuevo Leon ( Site 0057)

Monterrey, Nuevo León, Mexico

Instituto Nacional de Pediatria ( Site 0062)

Mexico City, , Mexico

Hospital Infantil de Mexico Federico Gomez ( Site 0061)

Mexico City, , Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0058)

Mexico City, , Mexico

Hospital Espanol ( Site 0059)

México, , Mexico

Instituto Nacional de Cancerologia. ( Site 0060)

México, , Mexico

Karolinska Universitetssjukhuset ( Site 0143)

Stockholm, Stockholms Lan [se-01], Sweden

Akademiska Sjukhuset ( Site 0144)

Uppsala, Uppsala Lan [se-03], Sweden

Sahlgrenska Universitetssjukhuset ( Site 0145)

Gothenburg, Vastra Gotalands Lan [se-14], Sweden

Countries

United States; Australia; Belgium; Brazil; Canada; Colombia; France; Germany; Mexico; Sweden

References

Wilck M, Cornely OA, Cordonnier C, Velez JD, Ljungman P, Maertens J, Selleslag D, Mullane KM, Nabhan S, Chen Q, Dagan R, Richmond P, Daus C, Geddie K, Tamms G, Sterling T, Patel SM, Shekar T, Musey L, Buchwald UK; V114-022 (PNEU-STEM) Study Group. A Phase 3, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate Safety, Tolerability, and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Allogeneic Hematopoietic Cell Transplant Recipients (PNEU-STEM). Clin Infect Dis. 2023 Oct 13;77(8):1102-1110. doi: 10.1093/cid/ciad349.

Reference Type: RESULT

PMID: 37338158 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

V114-022

Identifier Type: OTHER

Identifier Source: secondary_id

2018-000066-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V114-022

Identifier Type: -

Identifier Source: org_study_id