A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM)
Condition: Pneumococcal Infections
MeSH terms: Pneumococcal Infections
Intervention: V114; Prevnar 13™; PNEUMOVAX™23
Intervention description: 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.; 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; 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 MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 277.0
Sex: All
Minimum age: 3 Years
Healthy volunteers: No

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.