Immune Reconstitution Monitoring and Pneumococcal Vaccination in Patients Treated With CAR-T Cells

Phase 2WithdrawnNCT07071909

UNC Lineberger Comprehensive Cancer Center

Overview

This is a prospective interventional study designed to investigate the effect of Immune Reconstitution clinic visits and pneumococcal vaccination (PCV-21) on infection risk, anti-infective prophylaxis adherence, and vaccine response in patients receiving CAR-T therapy following lymphodepletion. Fifty subjects (20 receiving commercial CAR-T for CD19 or BCMA and 30 receiving investigational CAR-T) will be enrolled. Subjects will attend Immune Reconstitution Clinic Visits at 3, 6, 9, and 12 months after CAR-T cell infusion. Subjects will be asked to provide blood samples at pre-defined intervals during CAR-T visits which will be assessed for immune composition, vaccine titers, viral titers, and immunoglobulins. Samples will be primarily used for study purposes. Leftover blood will be stored for up to five years after the last study visit and may be used for future research. Vaccination against pneumococcal pneumonia will be offered at 6 months post-CAR-T infusion at the Immune Reconstitution Clinic Visit. Subjects will provide additional blood samples at 9- and 12 months post CAR-T infusion to assess anti-pneumococcal polysaccharide IgG antibodies to determine vaccine efficacy. Long-term follow-up will continue for up to 24 months post-CAR-T infusion via medical chart abstraction. This pilot study investigates immune reconstitution, infection risk, and vaccine response in patients receiving chimeric antigen receptor (CAR)-T cell therapy following lymphodepletion. Subjects will undergo lymphodepletion followed by CAR-T cell infusion will be included. The only additional treatment for subjects in this study is the PCV-21 pneumococcal vaccine. All CAR-T treatment procedures will adhere to the standard-of-care or the clinical trial protocol to which the subject is co-enrolled. Subjects will provide blood samples at predefined intervals during CAR-T visits. These samples will be assessed for various laboratory studies, including blood counts, immune cell composition, viral titers, immunoglobulins, and microbiome composition. Vaccination against pneumococcal pneumonia will be given 6 months post-CAR-T- T infusion. Subjects who opt for this vaccination will provide additional blood and blood samples at collected at 6, 9, and 12 months post-CAR-T infusion to assess anti-pneumococcal polysaccharide IgG antibodies. Long-term follow-up will continue for up to 24 months post-CAR-T infusion through medical chart abstraction

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. 2. The subject is willing and able to comply with study procedures based on the judgment of the investigator. 3. Age ≥ 18 years at the time of consent. 4. Planning to receive a commercial CD19 or BCMA-directed CAR-T therapy or investigational CD30 or solid tumor CAR-T therapy as a single infusion following lymphodepletion 5. Agree to provide blood samples as required by the protocol 6. Willing and able to provide access to immunization history 7. If receiving CAR-T as part of a clinical trial, must meet all eligibility criteria for that trial 8. Be willing to attend Immune Reconstitution Clinic Visits at 3, 6, 9, 12 months after CAR T-cell infusion 9. Be willing to receive PCV-21 vaccination at 6 months after CAR T-cell infusion. Exclusion Criteria: * None

Outcomes

Primary Outcomes

Anti-pneumococcal antibody concentrations

Anti-pneumococcal titers will be measured in CAR-T patients to determine proportion of patients receiving either CD19 or BCMA-directed CAR-T vs CD30 or solid tumor CAR-T who respond to PCV21 vaccination.

Time frame: Baseline, 3 and 6 months post vaccination

Secondary Outcomes

Number of reconstitution clinic visits

Number of reconstitution clinic visits (PCP prophylaxis including sulfamethoxazole trimethoprim, pentamidine, daponse, or atovqaqune and HSV proprophylaxis including valacyclovir or acyclovir) compared to historic controls.

Time frame: Up to 1 year

Difference in infection density

Difference in infection density of patients within one year post CAR-T cell therapy infusion who attend Immune Reconstitution Clinic Visits compared to historic controls.