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

Follicular Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04745559
• Other study ID #: MCC-20571
• Status: Recruiting
• Phase: Phase 2
• Start date: February 18, 2021
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: Ashley O'Neil
• Phone: 813-745-5240
• Email: ashley.oneil[@]moffitt.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: May 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large-Cell Lymphoma
• Follicular Lymphoma
• High-grade B-cell Lymphoma (HGBCL)
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
• Transformed Follicular Lymphoma (TFL)

Intervention

Biological:
• Pneumococcal conjugate vaccine (PCV13)
Licensed heptavalent pneumococcal conjugate vaccine (PCV13, Pneumococcal 13-valent conjugate vaccine
• CD19 targeted CAR T Cell Therapy
This is a personalized therapeutic approach that entails removal of T cells from patient's peripheral blood, genetic modification, activation and expansion in vitro to retarget cells against CD19 protein on the surface of B cells, and infusion of the genetically engineered cells back into the patient. CD19 is a surface protein that is expressed on B cells starting from early pre-B cells to mature fully differentiated B cells. Therefore, CD19-targeted CAR T cell therapy can effectively treat refractory B cell lymphomas.

Locations

Country	Name	City	State
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Humoral Response Rate -PCV13 vaccine	Humoral sero-protection rate elicited by the PCV13 vaccine intervention as measured on day+90 post CART	90 days post CAR T therapy
Secondary	Increase in PCV13 specific serotype IgG levels	PCV13 specific serotype IgG levels on day +90 post CAR T cell therapy as an absolute and as a change from baseline	90 days post CAR T therapy
Secondary	Increase in On-Specific Serotype IgG levels	Non-specific serotype IgG levels on day +90 post CAR T cell therapy as an absolute and as a change from baseline	90 days post CAR T therapy
Secondary	Response Rate of CD19-targeted CAR T therapy when combined with PCV13 vaccination	Percentage of patients whose cancer shrinks or disappears after treatment	90 days post CAR T therapy
Secondary	Progression Free Survival	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.	at 90 days and 180 days post CAR T therapy
Secondary	Overall Survival	Overall Survival (OS):The length of time from the start of treatment until death by any cause	180 days post CAR T therapy