Vaccine Responsiveness After CAR-T Cell Therapy

Rabies Vaccination to Assess Vaccine Responsiveness After B Cell Targeted CAR-T Cell Therapies

This phase I trial will use the inactivated rabies virus vaccine to assess immune function in patients who previously underwent B cell targeted chimeric antigen receptor-modified T cell immunotherapy (CARTx). A cohort of healthy volunteers will also be enrolled as a comparator group. CARTx is a new treatment for patients with B-cell malignancies (cancer of the B-cells), and the long-term effects of CARTx on immune function are not yet well understood. Learning more about vaccine responsiveness in patients who previously underwent CARTx may help doctors better understand immune function. The findings will guide evidence-based strategies for infection prevention to improve outcomes in this rapidly growing population of high-risk individuals.

Study Overview

• Status: Recruiting
• Conditions: B-Cell Neoplasm
• Intervention / Treatment: Procedure: Biospecimen Collection; Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine

Detailed Description

STUDY DESIGN:

This study will be a prospective, open-label clinical trial of primary and secondary vaccination with the inactivated rabies vaccine in patients treated with CARTx for B cell malignancies and healthy individuals. The target enrollment for this trial is 43 CARTx recipients and 10 healthy controls. The study is open to anyone regardless of gender or ethnicity.

OUTLINE:

BOLUS COHORT: Patients receive the inactivated rabies vaccine intramuscularly (IM) on day 1 and 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization. This will include up to 31 participants.

FRACTIONAL DOSE COHORT: Patients receive the inactivated rabies vaccine fractionated primary dose IM on days 1, 3, 7, 10, 14, and 17 and the second dose 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization. This will include up to 12 participants.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joshua A. Hill; Phone Number: 206-667-6504; Email: jahill3@fredhutch.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Contact: Joshua A. Hill; Phone Number: 206-667-6504; Email: jahill3@fredhutch.org
      • Principal Investigator: Joshua A. Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• CARTx RECIPIENTS: Patients must be capable of understanding and providing a written informed consent
• CARTx RECIPIENTS: Patients must be 18 years of age or older, of any gender, race or ethnicity
• CARTx RECIPIENTS: Patients must have had relapse-free survival for >= 6 months after receiving CARTx for B-cell malignancies
• CARTx RECIPIENTS: Platelet count > 30,000 / mm^3
• HEALTHY CONTROLS: Patients must be capable of understanding and providing a written informed consent
• HEALTHY CONTROLS: Patients must be 18 years of age or older, of any gender, race or ethnicity

Exclusion Criteria:

• CARTx RECIPIENTS: Patients who have received a hematopoietic cell transplant after CARTx
• CARTx RECIPIENTS: Previously received 1 or more rabies vaccines prior to the first vaccine visit
• CARTx RECIPIENTS: Patients who have received lymphodepleting therapies after CARTx and within the past 6 months
• CARTx RECIPIENTS: Patients with signs or symptoms of active infection
• CARTx RECIPIENTS: Patients who are pregnant or breastfeeding
• CARTx RECIPIENTS: Patients with previous known allergies to any component of the vaccine
• CARTx RECIPIENTS: Patients who have previously experienced a reaction to any vaccine that required medical attention
• CARTx RECIPIENTS: Study participants who report a severe adverse event following the first rabies vaccine will not be eligible for a second dose
• CARTx RECIPIENTS: Receiving corticosteroids > 0.5 mg/kg/day prednisone equivalence in the 7 days prior to first or second vaccination
• HEALTHY CONTROLS: Previously received 1 or more rabies vaccines
• HEALTHY CONTROLS: Chronic illness
• HEALTHY CONTROLS: Signs or symptoms of active infection
• HEALTHY CONTROLS: Pregnant or breastfeeding
• HEALTHY CONTROLS: Patients with previous known allergies to any component of the vaccine
• HEALTHY CONTROLS: Previous reaction to a vaccine that required medical attention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control (anti-rabies vaccine, collection of blood); Patients receive anti-rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo collection of blood samples at baseline, and at approximately 1, 2, and 4 weeks after each vaccination. There will be an additional blood draw 6 months (+/- 14 days) after the first immunization.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine; Given IM; Other Names: Imovax Rabies
Experimental: Experimental (anti-rabies vaccine, collection of blood); BOLUS COHORT: Patients receive the inactivated rabies vaccine IM on day 1 and 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization. FRACTIONAL DOSE COHORT: Patients receive the inactivated rabies vaccine fractionated primary dose IM on days 1, 3, 7, 10, 14, and 17 and the second dose 6-10 weeks later. Patients also undergo a blood collection prior to each vaccine, and at approximately 1, 2, and 4 weeks after each vaccination. A final blood collection occurs 6 months after the first immunization.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine; Given IM; Other Names: Imovax Rabies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with positive vaccine response	This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at week 4 post-secondary immunization. This RVNA titer is considered to be evidence of an adequate immune response by the World Health Organization. Will estimate with 95% confidence intervals.	4 weeks after the secondary vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with sustained vaccine response	This will be defined as a rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/ml at 6 months following the primary vaccination in participants who also receive secondary vaccination per-protocol	6 months after the primary vaccination
Longitudinal rabies virus neutralizing antibody (RVNA) titers	Will compare quantitative levels of RVNA (log10 IU/mL) between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.	From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.
Longitudinal rabies virus binding IgM antibody titers	Will compare quantitative levels of anti-rabies virus IgM between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.	From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.
Longitudinal rabies virus binding IgG antibody titers	Will compare quantitative levels of anti-rabies virus IgG between CAR-T cell therapy and healthy participants at weekly intervals after each vaccination and at 6 months after primary vaccination.	From baseline (prior to primary vaccination) through 6 months after primary vaccination based on measurements at weeks 0, 1, 2, 4, 6, 7, 8, 10, and 24.

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Joshua A. Hill, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2020
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: vaccine; infection; immunity; CAR T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: RG1007238; 10411 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2020-03444 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in a future article will be shared, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Data will be shared beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared to achieve aims in the approved proposal. Proposals should be directed to Joshua A. Hill. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No