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 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
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
49
Given IM
Undergo collection of blood samples
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
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.
Time frame: 4 weeks after the secondary vaccination
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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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