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

Overseen By Joshua A. Hill

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Corticosteroids

Disqualifiers: Hematopoietic transplant, Rabies vaccine, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand the immune system's response to a rabies vaccine in individuals who have previously received a new cancer treatment called CARTx, used for B-cell lymphoma (a type of blood cancer affecting certain white blood cells). The study will help doctors learn about immune function in these patients and how to prevent infections. Participants will include both individuals who have had CARTx and healthy volunteers to compare results. Those who have undergone CARTx and have been cancer-free for at least six months might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical insights.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that the Wistar rabies virus strain PM-1503-3M vaccine is safe for people. This vaccine helps the body produce antibodies that protect against rabies. Previous studies reported no major serious side effects from the vaccine. Most recipients might experience mild side effects, such as soreness at the injection site or a slight fever, which are common with many vaccines. These findings suggest that the vaccine is safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for B-cell lymphoma, which typically involve chemotherapy or targeted therapies, researchers are excited about this trial because it explores the immune response to a rabies vaccine following CAR-T therapy. This approach is unique because it investigates how well patients' immune systems can respond to vaccines after undergoing CAR-T therapy, a treatment that modifies the patient’s own T-cells to attack cancer cells. By analyzing the vaccine-induced immune response, researchers hope to gain insights into the broader immune recovery process, which could lead to improved post-CAR-T therapy care and better long-term outcomes for patients.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Studies have shown that the Wistar rabies virus strain PM-1503-3M vaccine effectively helps the body produce antibodies that specifically target rabies. These antibodies enable the immune system to recognize and fight the rabies virus. Research indicates that this vaccine is 100% effective in preventing deadly rabies infections in humans. This trial will administer the vaccine to participants to assess its effectiveness in patients who have undergone CAR-T therapy for B-cell lymphoma. Early findings suggest these patients might respond differently, and the trial aims to understand this better. Researchers will divide participants into groups to receive either a standard or fractional dose of the vaccine, collecting blood samples to evaluate the immune response. ^{1 2 3 4 6}

Who Is on the Research Team?

Joshua A. Hill

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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 have been free from cancer for at least 6 months after receiving CARTx therapy for B-cell cancer.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Published Research Related to This Trial

The Purified Chick Embryo Cell (PCEC) rabies vaccine has been shown to be safe and effective, with no reported deaths among 336 adverse event reports from 1997 to 2005.

Most adverse events (93%) following vaccination were non-serious and aligned with pre-licensure safety data, although there were some serious events, including hospitalizations and neurological issues, with no clear link to the vaccine.

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]

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]

The first-in-human trial of bispecific anti-CD20, anti-CD19 CAR T cells (LV20.19) demonstrated high efficacy, with an overall response rate of 82% and a complete response rate of 64% among 22 patients with relapsed, refractory B cell malignancies.

The treatment showed low toxicity, with only 5% of patients experiencing severe cytokine release syndrome and 14% experiencing severe neurotoxicity, indicating that on-site manufacturing and infusion of these CAR T cells is both feasible and safe.

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]

A 4-year-old boy experienced a severe allergic reaction to the lyophilized purified vero cell rabies vaccine (PVRV) after rabies exposure, highlighting the potential for allergic responses to components like animal-sourced gelatin in vaccines.

After receiving a new immunization regimen with a liquid PVRV without stabilizers, the boy developed adequate protective antibody levels against rabies, emphasizing the importance of tailoring vaccination strategies based on individual allergy histories.

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]

A study involving 242 healthy adults showed that the chromatographically purified rabies vaccine (CPRV) is immunogenic, achieving the WHO-recommended antibody levels by day 14 and maintaining them through day 90, similar to the human diploid cell vaccine (HDCV).

CPRV was associated with fewer local and systemic reactions compared to HDCV, with significantly lower rates of systemic events and no serious adverse reactions reported, indicating a favorable safety profile.

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]

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]

Influenza vaccination was found to be immunogenic in individuals both before and after receiving CAR-T cell therapy, even in the presence of conditions like hypogammaglobulinemia and B-cell aplasia.

The study suggests that vaccination against influenza and potentially other pathogens should be considered for patients undergoing CAR-T cell therapy, as a significant portion of them showed antibody responses post-vaccination.

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]

The purified rabies vaccine tested in various animal species showed no evidence of toxicity, even at doses equivalent to human administration, indicating its safety for use.

Both short- and long-term studies demonstrated that the vaccine did not cause any adverse reactions or changes in behavior, hematological parameters, or urinalysis in the tested animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In patients receiving anti-CD20 antibodies and cytotoxic chemotherapy for lymphomas, a third dose of the BNT162b2 vaccine improved CD4+Th1+T cell responses, indicating a potential benefit for enhancing immune response in severely immunosuppressed individuals.

However, the effect on CD8+ T cell responses was only marginal, suggesting that while the booster dose can help some aspects of the immune response, it may not be as effective for all T cell types.

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]

A study of 18 adults who received CAR-T cell therapy for B cell malignancies showed that vaccination against influenza can still elicit some immune response, even in individuals with low levels of immunoglobulins and B cells.

However, the overall effectiveness of the vaccine was lower in CAR-T cell recipients compared to non-immunocompromised controls, highlighting the need for additional infection prevention strategies in this vulnerable population.

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]

In a clinical trial involving 23 pediatric patients with relapsed/refractory Burkitt lymphoma, sequential CAR T-cell therapy targeting different B-cell antigens (CD19, CD22, and CD20) resulted in an estimated 18-month complete response rate of 78%, indicating a potential for durable responses in this population.

The therapy was found to be safe, with severe adverse events like cytokine release syndrome and neurotoxicity occurring primarily during the first infusion, and subsequent infusions showing significantly fewer severe side effects, all of which were reversible.

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]

In a study of 103 cord blood transplantation (CBT) recipients, vaccination responses were generally positive, with 60% of patients responding to Prevnar vaccines and high response rates (86% to 100%) for other vaccines like tetanus and diphtheria, despite some patients having graft-versus-host disease (GVHD) or prior rituximab treatment.

No vaccine side effects were reported, and all vaccinated patients survived, indicating that vaccination is safe and effective for CBT recipients, similar to those receiving adult donor transplants.

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]

The hamster kidney cell rabies vaccine, developed from the Beijing strain of rabies virus, met World Health Organization standards and produced satisfactory antibody responses in human volunteers.

In a study involving 301 individuals, including 97 bitten by rabid animals, none contracted rabies, demonstrating the vaccine's effectiveness and safety for postexposure use.

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]

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]

Citations

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Vaccine Responsiveness After CAR-T Cell Therapy | ... This phase I trial will use the inactivated rabies virus vaccine to assess immune function in patients who previously underwent B cell targeted chimeric ...

2. withpower.com withpower.com/trial/phase-1-lymphoma-b-cell-7-2020-db021

Vaccine Response After CAR-T Therapy for B-Cell Lymphoma What data supports the effectiveness of the treatment Wistar Rabies Virus Strain PM-1503-3M Vaccine for B-Cell Lymphoma? Research on therapeutic vaccines ...

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Wistar rabies virus strain PM-1503-3M vaccine Upon administration, Wistar rabies virus strain PM-1503-3M vaccine induces the formation of rabies-specific antibodies and rabies virus neutralizing antibodies ...

4. val-connect.ainfo.io val-connect.ainfo.io/clinical-trials/listings/9197/vaccine-responsiveness-after-car-t/?page=11&query=neoplasms&rnk=77

Vaccine Responsiveness After CAR-T Cell Therapy This phase I trial will use the inactivated rabies virus vaccine to assess immune function in patients who previously underwent B cell ...

5. wistar.org wistar.org/research-discoveries/business-development/discovery-pipelines/post-exposure-rabies-vaccine/

Post-exposure Rabies Vaccine 100% effective in preventing fatal rabies infection in humans. Wistar's rabies vaccine has helped to make rabies-related human death a rarity.

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[Results of preventive rabies vaccination with a ... [Results of preventive rabies vaccination with a concentrated vaccine of the PM/WI38-1503-3M rabies strain cultured on human diploid cells.