Clinical trial NCT04745559: Optimizing Cellular and Humoral Immunity by Vaccinating With PCV13 Before and After CAR-T Therapy
Official title: Optimizing Cellular and Humoral Immunity to Pneumococcus by Vaccination With Pneumococcal 13-valent Conjugate Vaccine Before and After CD19-targeted CAR T-cell Immunotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diffuse Large-Cell Lymphoma
Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
Transformed Follicular Lymphoma (TFL)
High-grade B-cell Lymphoma (HGBCL)
Follicular Lymphoma
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
First posted: 2021-02-09
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Humoral Response Rate -PCV13 vaccine
timeFrame: 90 days post CAR T therapy
Secondary outcomes:
measure: Increase in PCV13 specific serotype IgG levels
timeFrame: 90 days post CAR T therapy
measure: Increase in On-Specific Serotype IgG levels
timeFrame: 90 days post CAR T therapy
measure: Response Rate of CD19-targeted CAR T therapy when combined with PCV13 vaccination
timeFrame: 90 days post CAR T therapy
measure: Progression Free Survival
timeFrame: at 90 days and 180 days post CAR T therapy
measure: Overall Survival
timeFrame: 180 days post CAR T therapy
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
Study officials:
affiliation: Moffitt Cancer Center
name: Frederick Locke, MD
role: PRINCIPAL_INVESTIGATOR
References: