Clinical trial NCT03619252: Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
Official title: Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Myeloma
Pneumococcal Infection
Febrile Neutropenia
Pneumococcal Pneumonia
Lead sponsor: Minsk Scientific-Practical Center for Surgery, Transplantation and Hematology
Sponsor class: OTHER_GOV
Collaborators: name: Belarusian State Medical University
First posted: 2018-08-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Incidence of clinically/radiologically confirmed pneumonia and episodes of febrile neutropenia during one year period after initiation of novel agents.
timeFrame: One year
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
timeFrame: One year
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Minsk Scientific Practical Center of Surgery, Transplantation and Hematology, Belarus
Study officials:
affiliation: Minsk Scientific Practical Center of Surgery, Transplantation and Hematology, Belarus
name: Anatoly Uss, MD/PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.