Anti-pneumococcal Vaccine Strategy in Patients With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This phase II trial compares the effect of initial vaccination (PCV13 followed by PSV23) with yearly vaccinations of PSV23 to the standard 5 year vaccination in patients with chronic lymphocytic leukemia. At present chronic lymphocytic leukemia patients are poorly protected by anti-pneumococcal vaccination. Current vaccination schedule for chronic lymphocytic leukemia patients is based on general recommendations in immunocompromised patients (initial vaccination with PCV13 followed by one dose of PSV23 after an interval of two months, followed by revaccination at 5 years). Giving patients frequent immunization as compared to 5 year immunization may result in higher protective titers in patients.

Detailed Description
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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 pneumococcal 13-valent conjugate vaccine (PCV13) intramuscularly (IM) at week 1 and pneumococcal polyvalent vaccine (PSV23) IM at week 8. Patients then receive PSV23 IM booster at years 1, 2, 3, 4 and 5. ARM B: Patients receive PCV13 IM at week 1 and PSV23 IM at week 8. Patients then receive PSV23 IM booster at year 5.

Official Title
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Phase II Comparative Study of Anti-Pneumococcal Vaccine Strategy in Patients With Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Biological: Pneumococcal 13-valent Conjugate Vaccine
* Biological: Pneumococcal Polyvalent Vaccine


Participation Criteria
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Eligibility Criteria
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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 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 5-year survival expectation 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (yearly booster)<br>Patients receive PCV13 IM at week 1 and PSV23 IM at week 8. Patients then receive PSV23 IM booster at years 1, 2, 3, 4 and 5. | Biological: Pneumococcal 13-valent Conjugate Vaccine<br>* Given IM<br>* Other names: Prevnar 13;Biological: Pneumococcal Polyvalent Vaccine<br>* Given IM<br>* Other names: PPSV23 Vaccine;|
| Active Comparator: Arm B (5 year booster)<br>Patients receive PCV13 IM at week 1 and PSV23 IM at week 8. Patients then receive PSV23 IM booster at year 5. | Biological: Pneumococcal 13-valent Conjugate Vaccine<br>* Given IM<br>* Other names: Prevnar 13;Biological: Pneumococcal Polyvalent Vaccine<br>* Given IM<br>* Other names: PPSV23 Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with anti-pneumococcal immunogenicity following early revaccination (1 year) | 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. | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with anti-pneumococcal immunogenicity |  | At 5 years | 
| Proportion of patients with local and/or general reaction |  | At 1 and 3 months | 
| Number of pneumococcal infections |  | At 5 years |