Vaccine Response After CAR-T Therapy for B-Cell Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Joshua A. Hill

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Corticosteroids

Disqualifiers: Hematopoietic transplant, Rabies vaccine, Infection, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking corticosteroids at a dose higher than 0.5 mg/kg/day, you may not be eligible to participate.

What data supports the effectiveness of the treatment Wistar Rabies Virus Strain PM-1503-3M Vaccine for B-Cell Lymphoma?

Research on therapeutic vaccines for lymphomas shows that vaccines can induce immune responses capable of targeting and potentially eradicating lymphoma cells. Although some clinical trials have not shown prolonged survival, there are observations suggesting clinical efficacy, and ongoing efforts aim to improve vaccine strategies. ^{1 2 3 4 5}

Is the rabies vaccine safe for humans?

The rabies vaccine has been tested in various studies and is generally considered safe for humans. Most side effects are mild, such as pain at the injection site, headache, and muscle aches. Serious reactions are rare, and no vaccine-related serious adverse reactions were reported in the studies. ^{6 7 8 9 10}

How does the treatment for B-cell lymphoma differ from other treatments?

This treatment uses CAR-T cell therapy, which involves modifying a patient's own T cells to target specific proteins on cancer cells, making it a personalized and targeted approach. Unlike traditional treatments, it can be tailored to target multiple antigens, such as CD19 and CD20, potentially reducing the risk of cancer relapse due to antigen loss. ^{11 12 13 14 15}

Research Team

Joshua A. Hill

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults who've had B-cell targeted CAR-T cell therapy and been relapse-free for at least 6 months. It's also open to healthy adults as a comparison group. Participants must understand the study and consent in writing. Exclusions include pregnancy, breastfeeding, prior rabies vaccines, severe vaccine reactions, certain medication use, active infections, known allergies to vaccine components or medical attention-requiring reactions to any vaccine.

Inclusion Criteria

CARTx RECIPIENTS: Platelet count > 30,000 / mm^3

HEALTHY CONTROLS: Patients must be capable of understanding and providing a written informed consent

I am 18 or older and willing to participate as a healthy control.

Exclusion Criteria

I had a severe reaction to the first rabies vaccine and cannot take a second dose.

I am showing signs of an active infection.

You do not have any chronic illnesses.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the inactivated rabies vaccine. Blood samples are collected prior to each vaccine and at various intervals post-vaccination.

6-10 weeks

Multiple visits for vaccination and blood collection

Follow-up

Participants are monitored for immune response and safety, with blood collections continuing up to 6 months after the first vaccination.

6 months

Blood collection at 6 months post-vaccination

Treatment Details

Interventions

• Wistar Rabies Virus Strain PM-1503-3M Vaccine (Virus Therapy)

Trial Overview The trial tests immune function using an inactivated rabies virus vaccine in patients previously treated with CAR-T cell therapy compared to healthy volunteers. The goal is to learn how well these patients respond to vaccines after their cancer treatment and guide strategies for infection prevention.

Participant Groups

Group I: Experimental (anti-rabies vaccine, collection of blood) Experimental Treatment 2 Interventions

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.

Group II: Control (anti-rabies vaccine, collection of blood) Active Control 2 Interventions

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Fred Hutch/University of Washington Cancer Consortium Seattle, WA

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Patients Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Patients Recruited

1,341,000+

Findings from Research

Therapeutic vaccines targeting B cell lymphoma idiotype are showing promise in clinical trials, with ongoing phase III studies involving over 1000 patients, indicating a significant step towards personalized cancer treatment.

These idiotype vaccines have demonstrated few side effects and are believed to activate both anti-idiotype antibodies and cytotoxic T cells, enhancing the body's immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of therapeutic vaccines for non-Hodgkin's lymphoma. Hurvitz, SA., Timmerman, JM.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-SARS-CoV-2 cellular response after 2 and 3 doses of BNT162b2 mRNA vaccine in lymphoma patients receiving anti-CD20 antibodies. Gressens, SB., Wiedemann, A., Déchenaud, M., et al.[2023]

Therapeutic vaccines targeting lymphoma have been developed to stimulate the immune system to fight tumors, primarily using the unique idiotype of tumor B cells as a specific antigen.

Recent phase III trials did not show improved progression-free survival after chemotherapy with these vaccines, but ongoing research is focused on enhancing their effectiveness through better antigen delivery and boosting T cell responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccines for lymphomas: idiotype vaccines and beyond. Houot, R., Levy, R.[2022]

Combining cancer vaccines with autologous stem cell transplantation (PSCT) may help eliminate minimal residual disease in lymphoma patients, addressing the significant issue of relapse after high-dose therapy.

Preclinical studies have shown that vaccination with patient-specific immunoglobulin idiotype can effectively enhance T-cell responses when used alongside marrow transplantation, paving the way for ongoing clinical trials in human patients with B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor vaccination strategies combined with autologous peripheral stem cell transplantation. Kwak, LW.[2021]

Vaccines that activate NKT cells showed effectiveness in preventing the growth of CNS lymphoma in mouse models, indicating a promising approach for lymphoma treatment.

For established CNS lymphoma, the effectiveness of these vaccines can be improved by depleting regulatory T cells (Tregs) before vaccination, suggesting a need for combination strategies in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccines adjuvanted with an NKT cell agonist induce effective T-cell responses in models of CNS lymphoma. Grasso, C., Field, CS., Tang, CW., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rabies vaccine HDC: toxicological studies in laboratory animals. Ronneberger, H., Gruschkau, H., Majer, M.[2004]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine. Fang, Y., Liu, MQ., Chen, L., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety review of the purified chick embryo cell rabies vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS), 1997-2005. Dobardzic, A., Izurieta, H., Woo, EJ., et al.[2007]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity, safety and lot consistency in adults of a chromatographically purified Vero-cell rabies vaccine: a randomized, double-blind trial with human diploid cell rabies vaccine. Jones, RL., Froeschle, JE., Atmar, RL., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The primary hamster kidney cell rabies vaccine: adaptation of viral strain, production of vaccine, and pre- and postexposure treatment. Lin, F., Zeng, F., Lu, L., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Shah, NN., Johnson, BD., Schneider, D., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy. Walti, CS., Loes, AN., Shuey, K., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: a prospective observational study. Walti, CS., Loes, AN., Shuey, K., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. Liu, Y., Deng, B., Hu, B., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies. Shah, GL., Shune, L., Purtill, D., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Current status of therapeutic vaccines for non-Hodgkin's lymphoma. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-SARS-CoV-2 cellular response after 2 and 3 doses of BNT162b2 mRNA vaccine in lymphoma patients receiving anti-CD20 antibodies. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Vaccines for lymphomas: idiotype vaccines and beyond. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Tumor vaccination strategies combined with autologous peripheral stem cell transplantation. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Vaccines adjuvanted with an NKT cell agonist induce effective T-cell responses in models of CNS lymphoma. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Rabies vaccine HDC: toxicological studies in laboratory animals. [2004]

7. United States pubmed.ncbi.nlm.nih.gov

Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety review of the purified chick embryo cell rabies vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS), 1997-2005. [2007]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity, safety and lot consistency in adults of a chromatographically purified Vero-cell rabies vaccine: a randomized, double-blind trial with human diploid cell rabies vaccine. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

The primary hamster kidney cell rabies vaccine: adaptation of viral strain, production of vaccine, and pre- and postexposure treatment. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: a prospective observational study. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies. [2023]