Clinical Trials /

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

NCT04745559

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-20571
  • NCT ID: NCT04745559

Conditions

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

Interventions

DrugSynonymsArms
Pneumococcal conjugate vaccine (PCV13)Prevnar 13Treatment
CD19 targeted CAR T Cell TherapyTreatment

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalPneumococcal 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.
  • Pneumococcal conjugate vaccine (PCV13)
  • CD19 targeted CAR T Cell Therapy

Eligibility Criteria

        Inclusion Criteria:

          -  In good health as evidenced by medical history or diagnosed with relapsed or
             chemotherapy-refractory DLBCL, PMLBCL, TFL and HGBCL. Patients must be under
             consideration for treatment with CD19-targeted CAR T cell therapy with axicabtagene
             ciloleucel, 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 72 hours of
             administration of the first vaccine. Only women of childbearing potential will undergo
             serum 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.

          -  HIV infection confirmed by nucleic acid test (NAT), as evaluated during workup prior
             to CD19-targeted CAR T cell therapy

          -  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 <500 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate -PCV13 vaccine
Time Frame:90 days post CAR T therapy
Safety Issue:
Description:Response rate to PCV13 vaccine in eliciting protective humoral response (defined as IgG level greater than or equal to 1.3 ug/mL in more than 50% of evaluated PCV13 specific serotypes) on day +90 post CAR T cell therapy. The analysis of response will be conducted based on the Efficacy population and intention-to-treat (ITT) approach.

Secondary Outcome Measures

Measure:Increase in PCV13 specific serotype IgG levels
Time Frame:90 days post CAR T therapy
Safety Issue:
Description:The increase in PCV13 specific serotype IgG levels on day +90 post CAR T cell therapy from baseline as compared to the increase in non-specific serotype IgG levels
Measure:Response Rate of CD19-targeted CAR T therapy when combined with PCV13 vaccination
Time Frame:90 days post CAR T therapy
Safety Issue:
Description:Percentage of patients whose cancer shrinks or disappears after treatment
Measure:Progression Free Survival
Time Frame:at 90 days and 180 days post CAR T therapy
Safety Issue:
Description: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.
Measure:Overall Survival
Time Frame:180 days post CAR T therapy
Safety Issue:
Description:Overall Survival (OS):The length of time from the start of treatment until death by any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Last Updated

February 9, 2021