Febrile Neutropenia, Multiple Myeloma, Pneumococcal Infection, Pneumococcal Pneumonia
Conditions
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.
Detailed description
Multiple myeloma is an incurable blood cancer of plasma cells that occurs in older individuals with a median age at diagnosis of 69 years and a median overall survival of 6-7 years \[Kumar S.K., et al. Leukemia, 2014; Rollig C., et al. Lancet., 2015\]. Over the past years novel agents have been introduced into clinical practice, showing improved overall response rates, progression-free survival and overall survival in patients with multiple myeloma. The main classes of novel agents include proteasome inhibitors, immunomodulatory agents and monoclonal antibodies. These agents are typically used in doublet or triplet regimens that include a chemotherapeutic drug and/or corticosteroid. Streptococcus pneumoniae (pneumococcus) is a cause of worldwide morbidity and mortality. Patients with multiple myeloma are at high risk of developing life-threatening Streptococcus pneumoniae infections due to chemotherapy-associated immunosuppression. Vaccination is an important preventive strategy against infections caused by S. pneumoniae. In the past, the 23-valent pneumococcal polysaccharide vaccine was recommended. However, polysaccharide vaccines have limited efficacy in cancer and hematology patients, because of the decreased T- and B-cell responses. Clinical efficacy and safety of conjugate pneumococcal vaccines in multiple myeloma patients receiving novel agents have not been studied before. In this study the investigators wish to study the effect of vaccination with 13-valent pneumococcal conjugate vaccine in multiple myeloma patients treated with novel agents (proteasome inhibitors and immunomodulatory drugs). 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.
Interventions
BIOLOGICALVaccination with pneumococcal conjugate vaccine (PCV13)
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.
DRUGStandard Antibacterial Prophylaxis
Levofloxacin 500 mg once daily during the median four cycles of treatment by novel agents.
Sponsors
Belarusian State Medical University
Minsk Scientific-Practical Center for Surgery, Transplantation and Hematology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of clinically/radiologically confirmed pneumonia and episodes of febrile neutropenia during one year period after initiation of novel agents. | One year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | One year | Data on Common Terminology Criteria for Adverse Events (CTCAE v4.0) will be collected via questionnaires. Measurement data will be aggregated in electronic platform to characterize the frequency, severity and interference of symptomatic treatment toxicities. |
Countries
Belarus
Outcome results
None listed