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Vaccine Responsiveness After CAR-T Cell Therapy

Primary Purpose

B-Cell Neoplasm

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Wistar Rabies Virus Strain PM-1503-3M Vaccine
Biospecimen Collection
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for B-Cell Neoplasm focused on measuring CAR T cells, infection, vaccine, immunity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • CARTx RECIPIENTS: Patients must be capable of understanding and providing a written informed consent or, if a minor, have both parents or legal guardian be able to provide informed consent on their behalf
  • CARTx RECIPIENTS: Age ≥ 18 years old
  • 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: Age ≥ 18 years old

Exclusion Criteria:

  • CARTx RECIPIENTS: Patients who have received a hematopoietic cell transplant after CARTx
  • CARTx RECIPIENTS: Previously received 1 or more rabies vaccines
  • 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

Sites / Locations

  • Fred Hutch/University of Washington Cancer ConsortiumRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental (anti-rabies vaccine, collection of blood)

Control (anti-rabies vaccine, collection of blood)

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
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.
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.

Full Information

First Posted
May 28, 2020
Last Updated
October 2, 2023
Sponsor
Fred Hutchinson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04410900
Brief Title
Vaccine Responsiveness After CAR-T Cell Therapy
Official Title
Rabies Vaccination to Assess Vaccine Responsiveness After B Cell Targeted CAR-T Cell Therapies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 3, 2020 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-Cell Neoplasm
Keywords
CAR T cells, infection, vaccine, immunity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental (anti-rabies vaccine, collection of blood)
Arm Type
Experimental
Arm 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.
Arm Title
Control (anti-rabies vaccine, collection of blood)
Arm Type
Active Comparator
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Wistar Rabies Virus Strain PM-1503-3M Vaccine
Other Intervention Name(s)
Imovax Rabies
Intervention Description
Given IM
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected
Intervention Description
Undergo collection of blood samples
Primary Outcome Measure Information:
Title
Proportion of participants with positive vaccine response
Description
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
Secondary Outcome Measure Information:
Title
Proportion of participants with sustained vaccine response
Description
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
Title
Longitudinal rabies virus neutralizing antibody (RVNA) titers
Description
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.
Title
Longitudinal rabies virus binding IgM antibody titers
Description
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.
Title
Longitudinal rabies virus binding IgG antibody titers
Description
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joshua A. Hill
Phone
206-667-6504
Email
jahill3@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua A. Hill
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua A. Hill
Phone
206-667-6504
Email
jahill3@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Joshua A. Hill

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

Vaccine Responsiveness After CAR-T Cell Therapy

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