Vaccine Responsiveness After CAR-T Cell Therapy

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 1

Conditions: B-Cell Neoplasm

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04410900

10411 (Other Identifier)

RG1007238

NCI-2020-03444 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 2 patient groups

Experimental (anti-rabies vaccine, collection of blood)

Experimental group

Description:

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.

Treatment:

Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine

Procedure: Biospecimen Collection

Control (anti-rabies vaccine, collection of blood)

Active Comparator group

Description:

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.

Treatment:

Biological: Wistar Rabies Virus Strain PM-1503-3M Vaccine

Procedure: Biospecimen Collection