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Pneumococcal Pneumonia Vaccine Series (PCV20 and PPSV23) in Patients With Chronic Lymphocytic Leukemia Associated Immunodeficiency, PROTECT CLL Trial

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pneumococcal 20-valent Conjugate Vaccine
Pneumococcal Polyvalent Vaccine
Questionnaire Administration
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • NAIVE COHORT: Subjects must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL.
  • NAIVE COHORT: Male or female subject aged >= 18 years.
  • NAIVE COHORT: Subjects must not have received prior therapy for CLL.
  • VENETOCLAX-TREATMENT COHORT: Subjects must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL.
  • VENETOCLAX-TREATMENT COHORT: Subjects must have received venetoclax (any dose) for at least 12 months with the last dose =< 12 months prior to registration.

Exclusion Criteria:

  • Subjects who have experienced a severe allergic reaction to prior pneumonia vaccination.
  • Subjects who have received a pneumococcal vaccination in the last five years.
  • Active infection requiring topical or systemic therapy.
  • Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids:

    • Intranasal, inhaled, topical steroids, eye drops or local steroid injection (e.g., intra-articular injection);
    • Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent;
    • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
  • Concurrent illness or condition, which, in the opinion of the treating investigator, would negatively impact the subject's study participation.

Sites / Locations

  • Huntsman Cancer Institute/University of UtahRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (PCV20, PPSV23)

Arm II (PCV20, PPPSV23)

Arm Description

Patients receive pneumococcal 20-valent conjugate vaccine IM on day 1 and pneumococcal polyvalent vaccine IM on day 60 in the absence of disease progression or unacceptable toxicity.

Patients who have received or are receiving venetoclax therapy, receive pneumococcal 20-valent conjugate vaccine IM on day 1 and pneumococcal polyvalent vaccine IM on day 60 in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Proportion of patients who achieve the protocol defined change in antibody titers
Will examine the proportion of patients who achieve the protocol defined change in antibody titers from baseline in at least 6 of 12 S.pneumoniae serotypes shared between pneumococcal 20-valent conjugate vaccine (PCV20) and pneumococcal polyvalent vaccine (PPSV23) at 30 and 90 days post-PCV20 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported. A one sample exact binomial test will be performed at one-sided alpha = 0.05. The null hypothesis is that the proportion is 50% or lower.

Secondary Outcome Measures

Proportion of patients who have a two-fold increase of immunoglobulin levels
Will examine the proportion of patients who have a two-fold increase of immunoglobulin levels from baseline at 30 and 90 days and do not develop pneumonia within five years post-PPSV23 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported.
Proportion of vaccinated patients who have a two-fold increase in at least 6 of 12 S. pneumonia serotypes shared between PCV20 and PPSV23 vaccines
Will examine the proportion of vaccinated patients who have a two-fold increase in at least 6 of 12 S. pneumonia serotypes shared between PCV20 and PPSV23 vaccines and do not develop pneumonia within five years post PPSV23 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported.
Proportion of patients who have a two-fold increase in antibody titers to an individual serotype vaccination
Will examine the proportion of patients who have a two-fold increase in antibody titers to an individual serotype at 30 and 90 days post PPCV20 vaccination. The observed proportion and 95% exact binomial confidence intervals will be reported for each serotype.
Proportion of patients who maintain adequate immune response
Will examine the proportion of patients who maintain adequate immune response, defined as two-fold increase in antibody titers from baseline in 6/12 of S. pneumoniae serotypes, from PPSV23 vaccination to time of last follow-up at 5 years. Kaplan-Meier methods will be used to analyze time-to-pneumonia from baseline until five years after PPSV23 vaccination.

Full Information

First Posted
December 21, 2021
Last Updated
June 30, 2023
Sponsor
University of Utah
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05183854
Brief Title
Pneumococcal Pneumonia Vaccine Series (PCV20 and PPSV23) in Patients With Chronic Lymphocytic Leukemia Associated Immunodeficiency, PROTECT CLL Trial
Official Title
Phase II Study of the Efficacy of the Pneumococcal Pneumonia Vaccine Series in Patients With Chronic Lymphocytic Leukemia Associated Immunodeficiency (PROTECT CLL)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 7, 2022 (Actual)
Primary Completion Date
January 7, 2025 (Anticipated)
Study Completion Date
January 7, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Utah
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial tests whether the pneumococcal pneumonia vaccine series (PCV20 and PPSV23) works to mount an effective immune response in patients with chronic lymphocytic leukemia. PCV20 and PPSV23 are both vaccines that protect against bacteria that cause pneumococcal disease. Giving these vaccinations as series may make a stronger immune response and prevent against pneumococcal infections in patients with chronic lymphocytic leukemia.
Detailed Description
PRIMARY OBJECTIVE: I. To investigate the proportion of chronic lymphocytic leukemia (CLL) patients who mount an effective immune response to streptococcus pneumonia after receiving both pneumococcal 20-valent conjugate vaccine (PCV20) and pneumococcal polyvalent vaccine (PPSV23) vaccinations. (Primary Analysis) SECONDARY OBJECTIVES: I. To improve the immunoglobulin levels and decrease the incidence of pneumonia in patients with CLL-associated immunodeficiency. (Primary Analysis) II. To evaluate the rate of decreased pneumonia as assessed by an immune response to streptococcus (S.) pneumoniae after PCV20 and PPSV23 series versus PCV20 alone. (Primary Analysis) III. To investigate the immune response to individual S. pneumoniae serotypes included in both the PCV20 and PPSV23 vaccinations. (Primary Analysis) IV. Evaluate the length of time an effective immune response is maintained, and if the recommendation of 5 years is adequate for CLL patients. (Primary Analysis) EXPLORATORY OBJECTIVES: I. Assess rate of pneumonia in CLL patients based on therapeutic strategy (i.e., BTKi, venetoclax, chemo-immunotherapy). II. To evaluate the number of venetoclax treated CLL patients who mount an effective immune response to S. pneumoniae 30 days following both PCV20 and PPSV23 vaccinations. (Pilot Arm) OUTLINE: Patients are assigned to 1 of 2 arms. ARM I (PRIMARY ARM): Patients receive pneumococcal 20-valent conjugate vaccine intramuscularly (IM) on day 1 and pneumococcal polyvalent vaccine IM on day 60 in the absence of disease progression or unacceptable toxicity. ARM II (PILOT ARM): Patients who have received or are receiving venetoclax therapy, receive pneumococcal 20-valent conjugate vaccine IM on day 1 and pneumococcal polyvalent vaccine IM on day 60 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 90 days and then every 6 months for 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (PCV20, PPSV23)
Arm Type
Experimental
Arm Description
Patients receive pneumococcal 20-valent conjugate vaccine IM on day 1 and pneumococcal polyvalent vaccine IM on day 60 in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II (PCV20, PPPSV23)
Arm Type
Experimental
Arm Description
Patients who have received or are receiving venetoclax therapy, receive pneumococcal 20-valent conjugate vaccine IM on day 1 and pneumococcal polyvalent vaccine IM on day 60 in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Pneumococcal 20-valent Conjugate Vaccine
Other Intervention Name(s)
PCV 20, PCV 20 Vaccine, Prevnar 20
Intervention Description
Given IM
Intervention Type
Biological
Intervention Name(s)
Pneumococcal Polyvalent Vaccine
Other Intervention Name(s)
PCV 23, Pneumococcal 23-valent Polysaccharide Vaccine, Pneumococcal Polysaccharide Vaccine, Pneumococcal Vaccine Polyvalent, Pneumovax 23, Pnu-Imune 23, PPSV, PPSV23, PPSV23 Vaccine
Intervention Description
Given IM
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Proportion of patients who achieve the protocol defined change in antibody titers
Description
Will examine the proportion of patients who achieve the protocol defined change in antibody titers from baseline in at least 6 of 12 S.pneumoniae serotypes shared between pneumococcal 20-valent conjugate vaccine (PCV20) and pneumococcal polyvalent vaccine (PPSV23) at 30 and 90 days post-PCV20 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported. A one sample exact binomial test will be performed at one-sided alpha = 0.05. The null hypothesis is that the proportion is 50% or lower.
Time Frame
At 30 and 90 days post-PCV20 vaccination
Secondary Outcome Measure Information:
Title
Proportion of patients who have a two-fold increase of immunoglobulin levels
Description
Will examine the proportion of patients who have a two-fold increase of immunoglobulin levels from baseline at 30 and 90 days and do not develop pneumonia within five years post-PPSV23 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported.
Time Frame
Up to 5 years post- PPSV23 vaccination
Title
Proportion of vaccinated patients who have a two-fold increase in at least 6 of 12 S. pneumonia serotypes shared between PCV20 and PPSV23 vaccines
Description
Will examine the proportion of vaccinated patients who have a two-fold increase in at least 6 of 12 S. pneumonia serotypes shared between PCV20 and PPSV23 vaccines and do not develop pneumonia within five years post PPSV23 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported.
Time Frame
Up to 5 years post PPSV23 vaccination
Title
Proportion of patients who have a two-fold increase in antibody titers to an individual serotype vaccination
Description
Will examine the proportion of patients who have a two-fold increase in antibody titers to an individual serotype at 30 and 90 days post PPCV20 vaccination. The observed proportion and 95% exact binomial confidence intervals will be reported for each serotype.
Time Frame
At 30 and 90 days post-PCV20 vaccination
Title
Proportion of patients who maintain adequate immune response
Description
Will examine the proportion of patients who maintain adequate immune response, defined as two-fold increase in antibody titers from baseline in 6/12 of S. pneumoniae serotypes, from PPSV23 vaccination to time of last follow-up at 5 years. Kaplan-Meier methods will be used to analyze time-to-pneumonia from baseline until five years after PPSV23 vaccination.
Time Frame
Up to 5 years post PPSV23 vaccination
Other Pre-specified Outcome Measures:
Title
Number of patients that contract pneumonia
Description
Kaplan-Meier methods will be used to analyze time-to-pneumonia from baseline until five years after study entry, stratified by therapeutic strategy.
Time Frame
Up to 5 years post PPSV23 vaccination
Title
Proportion of venetoclax treated chronic lymphocytic leukemia (CLL) patients who achieve a two-fold increase in antibody titers
Description
Will examine the proportion of Venetoclax treated CLL patients who achieve a two-fold increase in antibody titers from baseline in at least 6 of 12 S. pneumonia serotypes shared between PCV20 and PPSV23 vaccines at 30 and 90 days post PCV20 vaccination.
Time Frame
At 30 and 90 days post PCV20 vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: NAIVE COHORT: Subjects must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. NAIVE COHORT: Male or female subject aged >= 18 years. NAIVE COHORT: Subjects must not have received prior therapy for CLL. VENETOCLAX-TREATMENT COHORT: Subjects must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. VENETOCLAX-TREATMENT COHORT: Subjects must have received venetoclax (any dose) for at least 12 months with the last dose =< 12 months prior to registration. Exclusion Criteria: Subjects who have experienced a severe allergic reaction to prior pneumococcal vaccination. Subjects who have received a PCV13 or PCV20 pneumococcal vaccination in the last five years. If they have received PPSV23 in ≥ 1 year and no other pneumococcal vaccine they may be included. Active infection requiring systemic antibiotic therapy. Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids: Intranasal, inhaled, topical steroids, eye drops or local steroid injection (e.g., intra-articular injection); Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication). Concurrent illness or condition, which, in the opinion of the treating investigator, would negatively impact the subject's study participation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine Cromar
Phone
801-213-5652
Email
catherine.cromar@hci.utah.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deborah M Stephens
Organizational Affiliation
Huntsman Cancer Institute/ University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deborah M. Stephens
Phone
801-585-0255
First Name & Middle Initial & Last Name & Degree
Deborah M. Stephens

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pneumococcal Pneumonia Vaccine Series (PCV20 and PPSV23) in Patients With Chronic Lymphocytic Leukemia Associated Immunodeficiency, PROTECT CLL Trial

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