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

Utah System of Higher Education (USHE)

Status and phase: Enrolling; Phase 2

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Biological: Pneumococcal 20-valent Conjugate Vaccine; Biological: Pneumococcal Polyvalent Vaccine; Other: Questionnaire Administration

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05183854

HCI145280 (Other Identifier)

P30CA042014 (U.S. NIH Grant/Contract)

NCI-2021-13373 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Arm I (PCV20, PPSV23)

Experimental group

Description:

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)

Treatment:

Other: Questionnaire Administration

Biological: Pneumococcal Polyvalent Vaccine

Biological: Pneumococcal 20-valent Conjugate Vaccine

Arm II (PCV20, PPPSV23)

Experimental group

Description:

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.

Treatment:

Other: Questionnaire Administration

Biological: Pneumococcal Polyvalent Vaccine

Biological: Pneumococcal 20-valent Conjugate Vaccine