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

Primary Purpose

Diffuse Large-Cell Lymphoma, Primary Mediastinal Large B-Cell Lymphoma (PMBCL), Transformed Follicular Lymphoma (TFL)

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Pneumococcal conjugate vaccine (PCV13)

CD19 targeted CAR T Cell Therapy

About this trial

This is an interventional treatment trial for Diffuse Large-Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Moffitt Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Humoral Response Rate -PCV13 vaccine

Humoral sero-protection rate elicited by the PCV13 vaccine intervention as measured on day+90 post CART

Secondary Outcome Measures

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

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

Response Rate of CD19-targeted CAR T therapy when combined with PCV13 vaccination

Percentage of patients whose cancer shrinks or disappears after treatment

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.

Overall Survival

Overall Survival (OS):The length of time from the start of treatment until death by any cause

Full Information

NCT ID

NCT04745559

First Posted

February 4, 2021

Last Updated

September 21, 2023

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT04745559

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 18, 2021 (Actual)

Primary Completion Date

February 2024 (Anticipated)

Study Completion Date

February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Pneumococcal conjugate vaccine (PCV13)

Other Intervention Name(s)

Prevnar 13

Intervention Description

Licensed heptavalent pneumococcal conjugate vaccine (PCV13, Pneumococcal 13-valent conjugate vaccine

Intervention Type

Biological

Intervention Name(s)

CD19 targeted CAR T Cell Therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Humoral Response Rate -PCV13 vaccine

Description

Humoral sero-protection rate elicited by the PCV13 vaccine intervention as measured on day+90 post CART

Time Frame

90 days post CAR T therapy

Secondary Outcome Measure Information:

Title

Increase in PCV13 specific serotype IgG levels

Description

PCV13 specific serotype IgG levels on day +90 post CAR T cell therapy as an absolute and as a change from baseline

Time Frame

90 days post CAR T therapy

Title

Increase in On-Specific Serotype IgG levels

Description

Non-specific serotype IgG levels on day +90 post CAR T cell therapy as an absolute and as a change from baseline

Time Frame

90 days post CAR T therapy

Title

Response Rate of CD19-targeted CAR T therapy when combined with PCV13 vaccination

Description

Percentage of patients whose cancer shrinks or disappears after treatment

Time Frame

90 days post CAR T therapy

Title

Progression Free Survival

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.

Time Frame

at 90 days and 180 days post CAR T therapy

Title

Overall Survival

Description

Overall Survival (OS):The length of time from the start of treatment until death by any cause

Time Frame

180 days post CAR T therapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ashley O'Neil

Phone

813-745-5240

ashley.oneil@moffitt.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frederick Locke, MD

Organizational Affiliation

Moffitt Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ashley O'Neil

Phone

813-745-5240

ashley.oneil@moffitt.org

First Name & Middle Initial & Last Name & Degree

Julio C Chavez, MD, MS

First Name & Middle Initial & Last Name & Degree

Marco Davila, MD, PhD

First Name & Middle Initial & Last Name & Degree

Michael Jain, MD, PhD

First Name & Middle Initial & Last Name & Degree

Farhad Khimani, MD

First Name & Middle Initial & Last Name & Degree

Aleksandr Lazaryan, MD, PhD, MPH

First Name & Middle Initial & Last Name & Degree

Dasom Lee, MD

First Name & Middle Initial & Last Name & Degree

Javier Pinilla, MD, PhD

First Name & Middle Initial & Last Name & Degree

Bijal D Shah, MD, MS

12. IPD Sharing Statement

Learn more about this trial

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

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