Vaccine Responsiveness After CAR-T Cell Therapy

NCT04410900 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: RG1007238NCI-2020-0344410411
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

B-Cell Neoplasm

Keywords

CAR T cells; infection; vaccine; immunity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Proportion of participants with sustained vaccine response

  6 months after the primary vaccination

• Longitudinal rabies virus neutralizing antibody (RVNA) titers

  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

  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

  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.

Study Arms (2)

Experimental (anti-rabies vaccine, collection of blood)

EXPERIMENTAL

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.

Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine; Procedure: Biospecimen Collection

Control (anti-rabies vaccine, collection of blood)

ACTIVE COMPARATOR

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.

Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine; Procedure: Biospecimen Collection

Interventions

Wistar Rabies Virus Strain PM-1503-3M Vaccine BIOLOGICAL

Given IM

Also known as: Imovax Rabies

Control (anti-rabies vaccine, collection of blood); Experimental (anti-rabies vaccine, collection of blood)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected

Control (anti-rabies vaccine, collection of blood); Experimental (anti-rabies vaccine, collection of blood)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Infections

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Joshua A. Hill

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 1, 2020
• Study Start: August 3, 2020
• Primary Completion: April 28, 2025
• Study Completion: August 31, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be shared beginning 3 months and ending 5 years following article publication.
• 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.

Locations

US (1)