Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents

NCT03619252 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: HEM-3_2
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma is an incurable blood cancer of plasma cells that occurs in older individuals. Novel agents (proteasome inhibitors, immunomodulatory agents) have substantially improved the overall response rates, progression-free survival and overall survival in patients with multiple myeloma. Patients with multiple myeloma are at high risk of developing life-threatening Streptococcus pneumoniae infections, while clinical efficacy and safety of conjugate pneumococcal vaccines in multiple myeloma patients receiving novel agents have not been studied before. The main aim of this study is to assess the clinical efficacy and safety of 13-valent pneumococcal conjugate vaccine in multiple myeloma patients treated with novel agents.

Conditions

Multiple Myeloma; Pneumococcal Infection; Febrile Neutropenia; Pneumococcal Pneumonia

Outcome Measures

Primary Outcomes (1)

• Incidence of clinically/radiologically confirmed pneumonia and episodes of febrile neutropenia during one year period after initiation of novel agents.

  One year

Secondary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

  One year

Study Arms (2)

Vaccination group

EXPERIMENTAL

Patients receiving novel agents (Bortezomib/Lenalidomide/Ixazomib/Daratumumab) and enrolled in vaccination by pneumococcal conjugate vaccine (PCV13): 3 doses with 1 month interval, and fourth dose planned to be administered 6 months later.

Biological: Vaccination with pneumococcal conjugate vaccine (PCV13)

Standard prophylaxis

ACTIVE COMPARATOR

Patients receiving novel agents (Bortezomib/Lenalidomide/Ixazomib/Daratumumab) and receiving standard institutional antibacterial prophylaxis by Levofloxacin 500 mg daily during the median four cycles of treatment by novel agents

Drug: Standard Antibacterial Prophylaxis

Interventions

Vaccination with pneumococcal conjugate vaccine (PCV13) BIOLOGICAL

Vaccination with pneumococcal conjugate vaccine - PCV13 (Prevnar 13/Prevenar 13, Pfizer Inc) containing saccharides from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F individually conjugated to nontoxic diphtheria cross-reactive material. Vaccination regimen: 3 doses monthly, with a booster dose 6 months later.

Vaccination group

Standard Antibacterial Prophylaxis DRUG

Levofloxacin 500 mg once daily during the median four cycles of treatment by novel agents.

Standard prophylaxis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with proven diagnosis of multiple myeloma
• Patients must be enrolled in treatment with novel agents (Bortezomib/Lenalidomide/Ixazomib/Daratumumab)
• Patients must have Creatinine Clearance above 30 mL/min on the Day 1 of trial
• Patients must have given informed consent to participate in trial.

You may not qualify if:

• Contraindication to the use of one of the study drug/vaccines (including known hypersensitivity)
• Creatinine Clearance below 30 mL/min on the Day 1 of trial
• Psychiatric disorder or unable to understand or to follow the protocol directions
• Active bacterial, viral, fungal or protozoal infection on the Day 1 of trial

Sponsors & Collaborators

• Minsk Scientific-Practical Center for Surgery, Transplantation and Hematology: lead
• Belarusian State Medical University: collaborator

Study Sites (1)

Minsk Scientific Practical Center of Surgery, Transplantation and Hematology, Belarus

Minsk, 220045, Belarus

Location

Related Publications (6)

• Wallington-Beddoe CT, Pitson SM. Novel therapies for multiple myeloma. Aging (Albany NY). 2017 Aug 28;9(8):1857-1858. doi: 10.18632/aging.101284. No abstract available.

  PMID: 28854147 BACKGROUND

• Satlin MJ, Vardhana S, Soave R, Shore TB, Mark TM, Jacobs SE, Walsh TJ, Gergis U. Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2015 Oct;21(10):1808-14. doi: 10.1016/j.bbmt.2015.06.017. Epub 2015 Jul 3.

  PMID: 26150022 BACKGROUND

• Jung SH, Kang SJ, Jang HC, Ahn JS, Yang DH, Lee SS, Kim YK, Kim HJ, Lee JJ. Effect of levofloxacin prophylaxis for prevention of severe infections in multiple myeloma patients receiving bortezomib-containing regimens. Int J Hematol. 2014 Nov;100(5):473-7. doi: 10.1007/s12185-014-1672-1. Epub 2014 Sep 12.

  PMID: 25212681 BACKGROUND

• 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.

  PMID: 25870329 BACKGROUND

• Stoma I, Karpov I, Iskrov I, Lendina I, Uss A. Clinical efficacy of pneumococcal vaccination in multiple myeloma patients on novel agents: Results of a prospective clinical study. Vaccine. 2020 Jun 19;38(30):4713-4716. doi: 10.1016/j.vaccine.2020.05.024. Epub 2020 May 14.

  PMID: 32418789 RESULT

• Zorger AM, Hirsch C, Baumann M, Feldmann M, Brockelmann PJ, Mellinghoff S, Monsef I, Skoetz N, Kreuzberger N. Vaccines for preventing infections in adults with haematological malignancies. Cochrane Database Syst Rev. 2025 May 21;5(5):CD015530. doi: 10.1002/14651858.CD015530.pub2.

  PMID: 40396505 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Pneumococcal Infections; Febrile Neutropenia; Pneumonia, Pneumococcal

Interventions

Vaccination; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Leukocyte Disorders; Pneumonia, Bacterial; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunotherapy, Active; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Anatoly Uss, MD/PhD

  Minsk Scientific Practical Center of Surgery, Transplantation and Hematology, Belarus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Cell Transplant Division

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: August 7, 2018
• Study Start: July 1, 2018
• Primary Completion: January 30, 2021
• Study Completion: June 30, 2021
• Last Updated: August 31, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)