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

Phase II Study of the Efficacy of the Pneumococcal Pneumonia Vaccine Series in Patients With Chronic Lymphocytic Leukemia Associated Immunodeficiency (PROTECT CLL)

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Other: Questionnaire Administration; Biological: Pneumococcal Polyvalent Vaccine; Biological: Pneumococcal 20-valent Conjugate Vaccine

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Catherine Cromar; Phone Number: 801-213-5652; Email: catherine.cromar@hci.utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute/University of Utah
      • Contact: Catherine Cromar; Phone Number: 801-213-5652; Email: catherine.cromar@hci.utah.edu
      • Contact: Lindsey Gilstrap; Phone Number: 801-213-5652; Email: lindsey.gilstrap@hci.utah.edu
      • Principal Investigator: Daniel Ermann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (PCV20, PPSV23); Patients receive pneumococcal 20-valent conjugate vaccine IM on day 1. PnumoVax23 will be given as an intramuscular injection on Visit 2 (approximately Day 75)	Other: Questionnaire Administration; Ancillary studies; Biological: Pneumococcal Polyvalent Vaccine; Given IM; Other Names: Pneumovax 23; PPSV23; Pneumococcal Vaccine Polyvalent; PCV 23; Pneumococcal 23-valent Polysaccharide Vaccine; Pneumococcal Polysaccharide Vaccine; Pnu-Imune 23; PPSV; PPSV23 Vaccine; Biological: Pneumococcal 20-valent Conjugate Vaccine; Given IM; Other Names: PCV 20; PCV 20 Vaccine; Prevnar 20
Experimental: Arm II (PCV20, PPPSV23); Patients who have received or are receiving venetoclax therapy, receive pneumococcal 20-valent conjugate vaccine IM at study visit 1 and pneumococcal polyvalent vaccine IM at study visit 2 in the absence of disease progression or unacceptable toxicity.	Other: Questionnaire Administration; Ancillary studies; Biological: Pneumococcal Polyvalent Vaccine; Given IM; Other Names: Pneumovax 23; PPSV23; Pneumococcal Vaccine Polyvalent; PCV 23; Pneumococcal 23-valent Polysaccharide Vaccine; Pneumococcal Polysaccharide Vaccine; Pnu-Imune 23; PPSV; PPSV23 Vaccine; Biological: Pneumococcal 20-valent Conjugate Vaccine; Given IM; Other Names: PCV 20; PCV 20 Vaccine; Prevnar 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 10 of 19 S.pneumoniae serotypes shared between pneumococcal 20-valent conjugate vaccine (PCV20) and pneumococcal polyvalent vaccine (PPSV23) at Study Visit 2 and 3. 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.	At 30 and 90 days post-PCV20 vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Study Visit 2 and 3 and do not develop pneumonia within five years post-PPSV23 vaccination. The observed proportion and an exact 95% binomial confidence interval will be reported.	Up to 5 years post- PPSV23 vaccination
Proportion of vaccinated patients who have a two-fold increase in at least 10 of 19 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 10 of 19 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.	Up to 5 years post PPSV23 vaccination
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 Study Visit 2 and 3 post PPCV20 vaccination. The observed proportion and 95% exact binomial confidence intervals will be reported for each serotype.	At 30 and 90 days post-PCV20 vaccination
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 10/19 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.	Up to 5 years post PPSV23 vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients that contract pneumonia	Kaplan-Meier methods will be used to analyze time-to-pneumonia from baseline until five years after study entry, stratified by therapeutic strategy.	Up to 5 years post PPSV23 vaccination
Proportion of venetoclax treated chronic lymphocytic leukemia (CLL) patients who achieve a two-fold increase in antibody titers	Will examine the proportion of Venetoclax treated CLL patients who achieve a two-fold increase in antibody titers from baseline in at least 10 of 19 S. pneumonia serotypes shared between PCV20 and PPSV23 vaccines at Study Visit 2 and 3.	At 30 and 90 days post PCV20 vaccination

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel Ermann, MD, Huntsman Cancer Institute/ University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2022
• Primary Completion (Estimated): January 7, 2025
• Study Completion (Estimated): January 7, 2027

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: December 21, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Leukemia, B-Cell; Pneumococcal Infections; Chronic Disease; Leukemia; Pneumonia; Pneumonia, Pneumococcal; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: HCI145280 (Other Identifier: Huntsman Cancer Institute/University of Utah); P30CA042014 (U.S. NIH Grant/Contract); NCI-2021-13373 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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