Safety and Immunogenicity of V114 in Recipients of Allo-HSCT

Phase 1

• Conditions: Pneumococcal disease; MedDRA version: 20.0Level: PTClassification code 10061353Term: Pneumococcal infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2018-000066-11-FR
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-06-29
• Last Update Posted: 6 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Received a human leukocyte antigen (HLA) compatible donor including haploidentical and mismatched (related or unrelated) first allo-HSCT (ie, bone marrow or peripheral blood stem cell) 90 to 180 days prior to randomization (Visit 2).
2. Received the allo-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, aplastic anemia, or sickle cell disease.
3. Life expectancy >12 months after allo-HSCT, according to investigator judgement.
4. Clinically stable engraftment according to investigator judgment.
5. Participant is Male or Female =18 years of age.
6. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Protocol.
OR
b. A WOCBP who agrees to use 1 of the contraceptive methods as defined in Protocol during the treatment period and for at least 6 weeks after the last dose of study intervention.
7. The participant provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Receipt of a previous allo-HSCT.
2. Received allo-HSCT with ex-vivo graft manipulation (e.g. CD34 selection, TCR alpha beta depletion, etc), in vivo T cell depletion with alemtuzumab, or haploidentical allo- HSCT with high dose anti-thymocyte globulin.
3. Received allo-HSCT for:
- Multiple myeloma
- Any nonmalignant diseases
4. Persistent or relapsed primary disease (diagnosed as per the investigator’s institution’s morphologic criteria for refractory or relapse of disease) after allo-HSCT.
5. History of severe GVHD (Grade 3 or 4 GVHD) after allo-HSCT
6. Planned organ transplantation after allo-HSCT.
7. History of culture-positive pneumococcal disease occurring after allo-HSCT (eg, positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site).
8. Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine.
9. History of congenital immunodeficiency or specific acquired immunodeficiency such as documented HIV infection, or anatomic asplenia.
10. Coagulation disorder contraindicating intramuscular vaccinations.
11. *Recent febrile illness (defined as oral or tympanic temperature =100.4°F [=38.0°C]; axillary or temporal temperature =99.4°F [=37.4°C]; or rectal temperature =101.4°F [=38.6°C]) or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of study vaccine.
12. Severe hepatic impairment (defined as Child-Pugh Class C) at Screening (Visit 1).
13. Serum aspartate transaminase (AST) or alanine transaminase (ALT) >5 × upper limit of normal (ULN) or serum total bilirubin >2.5 × ULN at Screening (Visit 1).
14. *Grade =4 renal impairment (estimated glomerular filtration rate <30 ml/min/1.73m2 or dialysis) at Screening (Visit 1).
15. *Platelet count <30,000/µL at Screening (Visit 1).
16. *Absolute neutrophil count <1,000/µL at Screening (Visit 1).
17. A WOCBP who has a positive urine or serum pregnancy test before the 1st vaccination at Visit 2.
18. Received chimeric antigen receptor T-cell (CAR-T) therapy or checkpoint inhibitor directed therapy (ie, anti PD-1) after allo-HSCT.
19. Received anti- CD20 B-cell targeted therapy (eg, rituximab) after allo-HSCT.
20. *Received systemic steroids at a prednisone equivalent dose >0.5 mg/kg/day (steroids at a prednisone equivalent dose =0.5 mg/kg/day are allowed) for =14 consecutive days and has not completed treatment at least 30 days before administration of any study vaccine.
21. *Scheduled to receive immunoglobulins or plasma products within 30 days of administration of study vaccine.
22. Non-study pneumococcal vaccine administered after allo-HSCT, or is expected to receive non-study pneumococcal vaccine during participation in the study.
23. *Received any licensed, non-live vaccine within 14 days before receipt of any study vaccine, or is scheduled to receive any licensed, non-live vaccine within 14 days after receipt of any study vaccine.
24. *Received any live vaccine within 30 days before receipt of any study vaccine or is scheduled to receive any live vaccine within 30 days after receipt of any study vaccine.
25. 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified