Clinical trial NCT03565900: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)
Official title: A Phase 3, Randomized, Double-blind, Active Comparator-controlled, Multicenter Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Recipients of Allogeneic Hematopoietic Stem Cell Transplant (PNEU-STEM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-06-21
Enrollment: 277
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 \[GVHD\]).


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.

Primary outcomes:
measure: Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
timeFrame: Up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
measure: Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
timeFrame: Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
measure: Adult Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
timeFrame: Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
measure: Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™
timeFrame: Up to 14 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™)
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event Up to Month 12 After Allogeneic HSCT
timeFrame: Up to 9 months
measure: Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
timeFrame: Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
Secondary outcomes:
measure: Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23
timeFrame: Up to 5 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Pediatric Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With PNEUMOVAX™23
timeFrame: Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Adult Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23
timeFrame: Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Pediatric Participants: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With PNEUMOVAX™23
timeFrame: Up to 14 days after the PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With PNEUMOVAX™23
timeFrame: Up to 1 month after PNEUMOVAX™23 vaccination (12 months after HSCT and approximately 6 to 10 months after Day 1)
measure: Adult Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™
timeFrame: Up to 5 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Pediatric Participants With GVHD: Percentage of Participants With a Solicited Injection-site Adverse Event Following Dose 4 With V114 or Prevnar 13™
timeFrame: Up to 14 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Adult Participants With GVHD: Percentage of Participants With a Solicited Systemic Adverse Event Following Dose 4 With V114 or Prevnar 13™
timeFrame: Up to 14 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Pediatric Participants With GVHD: Percentage of Participants With a Solicited Systemic Adverse Event Following Dose 4 With V114 or Prevnar 13™
timeFrame: Up to 14 days after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 9 months after Day 1)
measure: Participants With GVHD: Percentage of Participants With a Vaccine-related Serious Adverse Event Following Dose 4 With V114 or Prevnar 13™
timeFrame: Up to 6 months after the fourth V114 or Prevnar 13™ vaccination (12 months after HSCT and approximately 6 to 15 months after Day 1)
measure: Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
timeFrame: Up to Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
measure: Percentage of Participants With Geometric Mean Fold Rises (GMFR) ≥4 in Serotype-specific IgG at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
timeFrame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
measure: Percentage of Participants With GMFR ≥4 in Serotype-specific OPA at 30 Days Following Dose 3 With V114 or Prevnar 13™ (Day 90)
timeFrame: Time Frame: Day 1 (Baseline) and Day 90 (30 days after the Day 60 vaccinations with V114 or Prevnar 13™)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Health Care ( Site 0005)
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado ( Site 0166)
state: Colorado
city: Gainesville
country: United States
facility: University of Florida ( Site 0011)
state: Florida
city: Chicago
country: United States
facility: University of Chicago ( Site 0016)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation ( Site 0001)
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center ( Site 0007)
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins - University ( Site 0023)
state: Maryland
city: Kansas City
country: United States
facility: Children's Mercy Hospital ( Site 0167)
state: Missouri
city: Bronx
country: United States
facility: Montefiore Einstein Center ( Site 0164)
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0010)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation ( Site 0168)
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University ( Site 0018)
state: Oregon
city: Houston
country: United States
facility: Baylor College of Medicine - Texas Children's Hospital ( Site 0165)
state: Texas
city: Sydney
country: Australia
facility: St. Vincent's Hospital ( Site 0041)
state: New South Wales
city: Westmead
country: Australia
facility: The Children s Hospital at Westmead ( Site 0191)
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital ( Site 0040)
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health-Austin Hospital ( Site 0038)
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital ( Site 0037)
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital ( Site 0039)
state: Victoria
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc ( Site 0122)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 0119)
state: Vlaams-Brabant
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge-Oostende ( Site 0118)
state: West-Vlaanderen
city: Roeselare
country: Belgium
facility: AZ Delta ( Site 0120)
state: West-Vlaanderen
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0121)
city: Salvador
country: Brazil
facility: Hospital Sao Rafael ( Site 0049)
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte ( Site 0050)
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Instituto de Cancer e Transplante de Curitiba ICTR ( Site 0051)
state: Paraná
city: Halifax
country: Canada
facility: Nova Scotia Health Authority QEII-HSC ( Site 0033)
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre ( Site 0032)
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0031)
state: Quebec
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe ( Site 0077)
state: Antioquia
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 0073)
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali S.A ( Site 0075)
state: Valle Del Cauca
city: Nice
country: France
facility: CHU de Nice ( Site 0084)
state: Alpes-Maritimes
city: Besancon
country: France
facility: Hopital Jean Minjoz Besancon ( Site 0085)
state: Doubs
city: La Tronche
country: France
facility: CHU de Grenoble Hopital Nord ( Site 0083)
state: Isere
city: Lille
country: France
facility: CHRU de Lille - Hopital Claude Huriez ( Site 0090)
state: Nord
city: Creteil
country: France
facility: CHU Henri Mondor ( Site 0081)
state: Val-de-Marne
city: Paris
country: France
facility: Hopital Saint-Antoine ( Site 0089)
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf ( Site 0107)
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln ( Site 0105)
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitaetsmedizin Mainz ( Site 0106)
state: Rheinland-Pfalz
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez ( Site 0187)
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Servicio de hematologia Universidad Autonoma de Nuevo Leon ( Site 0057)
state: Nuevo Leon
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Pediatria ( Site 0062)
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0058)
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez ( Site 0061)
city: Mexico
country: Mexico
facility: Hospital Espanol ( Site 0059)
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia. ( Site 0060)
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset ( Site 0143)
state: Stockholms Lan [se-01]
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset ( Site 0144)
state: Uppsala Lan [se-03]
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset ( Site 0145)
state: Vastra Gotalands Lan [se-14]
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.