Optimizing Cellular and Humoral Immunity by Vaccinating With PCV13 Before and After CAR-T Therapy

Phase 2

Active, not recruiting

• Conditions: Primary Mediastinal Large B-Cell Lymphoma (PMBCL); Follicular Lymphoma; Diffuse Large-Cell Lymphoma; Transformed Follicular Lymphoma (TFL); High-grade B-cell Lymphoma (HGBCL)
• Interventions: Biological: Pneumococcal conjugate vaccine (PCV13); Biological: CD19 targeted CAR T Cell Therapy

• Registration Number: NCT04745559
• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Brief Summary

The purpose of the study is to evaluate whether receiving the pneumococcal 13-valent conjugate vaccine (PCV13) before and after CD19-targeted CAR T cell therapy will optimize cellular and humoral immunity to pneumococcus.

Detailed Description

This is a phase II, single-institution study to investigate if pneumococcal vaccination before and after CD19-targeted CAR T cell therapy elicits cellular and humoral immunity to pneumococcus in patients with relapsed or refractory B cell lymphomas. All the participants will receive the same treatment. Immunoglobulins (IgG) against pneumococcal serotypes not included in the vaccine will be served as an internal control. Treatment includes the same dose (0.5ml) of PCV13 one time prior to apheresis followed by two times after CAR T cell therapy

Study Timeline

• Study First Submitted: 2021-02-04
• Study First Submitted QC: 2021-02-04
• Study First Posted: 2021-02-09
• Study Start: 2021-02-18
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-17
• Primary Completion: 2025-05-28
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• In good health as evidenced by medical history or diagnosed with relapsed or chemotherapy-refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMLBCL), transformed follicular lymphoma (TFL) high-grade B cell lymphoma (HGBCL) or Follicular Lymphoma. Patients must be under consideration for treatment with any CD19-targeted CAR T cell therapy, per institutional standards. Patients undergoing active vital organ testing with a planned apheresis date for CAR T cell therapy may be considered eligible.
• Signed informed consent form in accordance with institutional and federal law policies
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, age over 18
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation

Exclusion Criteria

• Pregnant or lactating woman, as evaluated by serum testing within 2 weeks of administration of the first vaccine. Only women of childbearing potential will undergo serum/urine pregnancy testing. A woman will be considered of childbearing potential unless she is status-post hysterectomy or tubal ligation or without menstrual periods in the preceding 12 months.
• Common variable immunodeficiency or other inherited systemic immunodeficiency syndrome
• History of severe allergy (e.g., anaphylaxis) to any component of pneumococcal conjugate vaccine 7 valent (PCV7), PCV13, or any diphtheria-toxoid containing vaccine.
• Inclusion on a separate trial in which patients may be randomized or otherwise started on maintenance chemotherapies within the first 3 months of CD19-targeted CAR T cell therapy
• Patients with significant psychiatric illness likely to affect compliance, as determined by the treating physician
• Active or uncontrolled infections
• Platelet count <10,000 cells/microliter
• Lymphocyte count <200 cells/microliter
• Intervenous immunoglobulin (IVIG) administration within one month of planned apheresis for collection for CD19-targeted CAR T cell manufacture
• History of PCV13 administration within one month of planned apheresis for collection for CD19-targeted CAR T cell manufacture

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Pneumococcal conjugate vaccine (PCV13)	Pneumococcal conjugate vaccine (PCV13) .5 ml will be administered intramuscularly three times: 7 days (range 4 to 21 days) before apheresis collection and on day +30 (range +21 to +37) and day +90 (range +75 to +115) after CAR T cell infusion.
Treatment	CD19 targeted CAR T Cell Therapy	Pneumococcal conjugate vaccine (PCV13) .5 ml will be administered intramuscularly three times: 7 days (range 4 to 21 days) before apheresis collection and on day +30 (range +21 to +37) and day +90 (range +75 to +115) after CAR T cell infusion.

Primary Outcome Measures

Name	Time	Method
Humoral Response Rate -PCV13 vaccine	90 days post CAR T therapy	Humoral sero-protection rate elicited by the PCV13 vaccine intervention as measured on day+90 post CART

Secondary Outcome Measures

Name	Time	Method
Response Rate of CD19-targeted CAR T therapy when combined with PCV13 vaccination	90 days post CAR T therapy	Percentage of patients whose cancer shrinks or disappears after treatment
Increase in PCV13 specific serotype IgG levels	90 days post CAR T therapy	PCV13 specific serotype IgG levels on day +90 post CAR T cell therapy as an absolute and as a change from baseline
Increase in On-Specific Serotype IgG levels	90 days post CAR T therapy	Non-specific serotype IgG levels on day +90 post CAR T cell therapy as an absolute and as a change from baseline
Overall Survival	180 days post CAR T therapy	Overall Survival (OS):The length of time from the start of treatment until death by any cause
Progression Free Survival	at 90 days and 180 days post CAR T therapy	Progression Free Survival (PFS) from start of treatment to death of any cause, disease progression or relapse of the date of last follow-up, whichever comes first.

Trial Locations

Locations (1)

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States