Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents

Study Overview
=================
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.

Official Title
-----------------
Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents

Conditions
-----------------
Multiple Myeloma, Pneumococcal Infection, Febrile Neutropenia, Pneumococcal Pneumonia

Intervention / Treatment
-----------------
* Biological: Vaccination with pneumococcal conjugate vaccine (PCV13)
* Drug: Standard Antibacterial Prophylaxis


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccination group<br>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)<br>* 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.<br>|
| Active Comparator: Standard prophylaxis<br>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<br>* Levofloxacin 500 mg once daily during the median four cycles of treatment by novel agents.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | 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. | One year |