Anti-pneumococcal Vaccine Strategy in Patients With Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVE:

I. Proportion of patients with anti-pneumococcal immunogenicity following early revaccination (1 year) at 2 years (Serotype to be measured are 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A 19 F and 23F using the enzyme-linked immunosorbent assay [ELISA] method).

SECONDARY OBJECTIVES:

I. Number of patients with anti-pneumococcal immunogenicity at 5 years. II. Number of patients with local and/or general reaction at months 1, 3 as self-reported.

III. Number of pneumococcal infections.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive PCV 20 IM at week 0. Titers will be checked 4 weeks after this dose. Booster Vaccine: None. Titers will be checked at 12 weeks and then yearly for 5 years.

ARM B: Patients receive PCV 20 IM at week 0 and PSV23 IM at week 8. Titers will be checked 4 weeks after the first dose and at 12 weeks (4 weeks after the second dose). Booster Vaccine: None. Annual titers will be checked for 5 years.

ARM C: Patients receive PCV 20 IM at week 0 and PSV23 IM at week 8. Titers will be checked 4 weeks after the first dose and at 12 weeks (4 weeks after the second dose). Booster Vaccine: PCV23 booster vaccination dose will be administered yearly for 5 years. Pre-vaccination and post-vaccination (at 4 weeks) titers will be checked each time yearly for 5 years.

Inclusion criteria

• Men and women >= 18 years of age
• Patients must have histologically identified chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) as defined by the World Health Organization (WHO) classification of hematopoietic neoplasms
• Treatment naive CLL/SLL; No prior therapy for CLL/SLL, including chemotherapy and/or radiotherapy is allowed
• Estimated life expectancy of greater than 24 months

Exclusion criteria

• Patients with neutropenic (granulocyte [PMN]s < 500 cells/mm^3) or having received rituximab within 6 months
• Patients with fever (temperature > 38 degrees Celsius [C]) within 1 week
• Active infection, recent infection requiring systemic treatment that was completed =< 14 days before starting treatment on the study
• Patients with known human immunodeficiency virus (HIV) infection
• History of allergic reactions attributable to compounds of similar chemical or biologic composition to any component of pneumococcal vaccines
• Chemotherapy in 4 weeks or received Rituximab or similar anti CD20 monoclonal antibody for non-hematological indications within 6 months
• Received intravenous immunoglobulin (IVIG) within 3 months prior to vaccination
• History of allogenic stem cell transplantation
• Patients who have received cellular therapy (e.g. CAR-T cells) within 12 months prior to vaccination
• Patients who have previously received pneumococcal vaccine within the preceding 12 months
• Absolute lymphocyte count less than 500 cells/mm^3
• Patient with other severe immune deficiency
• Patients may not be receiving any other investigational agents
• Active malignancy from which the subject is considered by his or her physician to have a less than 24 month survival expectation. Non-melanoma skin cancer is not an exclusion criterion.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and/or psychiatric illness/social situations that would limit compliance with study requirements
• Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration [> 14 days] of > 20 mg/day of prednisone) within 14 days of the first dose of study drug
• Because of the potential for H2-blockers to modulate antibody response to pneumococcal vaccine, patients must discontinue treatment with H2-blockers (cimetidine, ranitidine, etc.) prior to beginning protocol therapy
• Unwilling or unable to participate in all required study evaluations and procedures
• Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)