CAR T-Cells + CMV Vaccine for Non-Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Prior stem cell transplant, Autoimmune disease, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for high-grade B-cell non-Hodgkin lymphoma, a type of blood cancer. It combines CAR T-cells—special immune cells modified to attack cancer—with a vaccine (Multi-peptide CMV-Modified Vaccinia Ankara Vaccine) that may enhance the immune response. The trial aims to determine if this combination is safe and effective in preventing cancer recurrence after a stem cell transplant. Individuals with B-cell non-Hodgkin lymphoma that has returned after treatment or did not respond to initial treatment, and who are already CMV-positive, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you do not use systemic steroids or chronic immunosuppressant medications. Inhaled or topical steroids in standard doses are allowed, and low-dose steroid replacement is permitted. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that anti-CD19 CAR T-cell treatments have generally been well-tolerated by patients with B-cell non-Hodgkin lymphoma. Some studies have noted side effects, but these are often manageable. Common issues include fever and low blood cell counts, which are usually temporary.

Regarding the CMV-MVA triplex vaccine, earlier studies found it to be safe for patients. Some mild side effects, like tiredness and soreness at the injection site, have been reported.

Since this trial involves both treatments, it's important to remember that these findings are preliminary. The trial is in an early phase, so researchers are still closely monitoring safety and side effects. However, existing data suggests that both treatments have been well-tolerated individually in the past. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the CAR T-Cells + CMV Vaccine treatment for Non-Hodgkin's Lymphoma because it harnesses the body's own immune system in a unique way. Unlike traditional chemotherapy, which targets rapidly dividing cells broadly, this treatment uses engineered T-cells that specifically target and destroy cancer cells expressing the CD19 protein. Additionally, the use of a CMV vaccine aims to boost the immune response, potentially increasing the effectiveness of the CAR T-cells. This targeted approach could lead to more effective and less toxic treatments for patients.

What evidence suggests that this treatment might be an effective treatment for non-Hodgkin's lymphoma?

Research shows that CD19-targeted CAR T-cells effectively treat B-cell non-Hodgkin lymphoma, especially when the disease returns or resists other treatments. Participants in this trial will receive CMV-specific CD19-CAR T-cells, which studies have found can lead to strong and lasting improvements, meaning the treatment continues to work over time. Additionally, participants will receive the CMV-MVA triplex vaccine, designed to enhance the immune system's ability to fight cancer cells. While researchers are still studying this combination, there is hope it might prevent lymphoma from returning after treatment. Early results suggest this could be a powerful new option for patients with this type of cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Alex F. Herrera

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with certain types of B-cell non-Hodgkin lymphoma, who are in first relapse or didn't respond to initial treatment. They must be CMV positive, have a good performance status (able to carry out daily activities), and proper organ function. Pregnant women, those with prior stem cell transplants, autoimmune diseases needing steroids, other active cancers or infections can't join.

Inclusion Criteria

Total serum bilirubin =< 2.0 mg/dL.

Patient must be CMV seropositive.

Alanine aminotransferase (ALT) < 2.5 x ULN.

Exclusion Criteria

I do not have any uncontrolled serious illnesses.

I have had a stem cell transplant using my own or a donor's cells.

Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Patients receive standard conditioning regimen (typically carmustine, etoposide, cytarabine, melphalan) beginning approximately on day -9

9 days

Transplantation

Patients undergo autologous hematopoietic stem cell transplantation (autoHSCT) on day -2

1 day

CAR T-Cells and Vaccination

Patients receive CMV-specific CD19-CAR T cells intravenously on day 0 and CMV-MVA triplex vaccine intramuscularly on days 28 and 56

56 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Anti-CD19-CAR CMV-specific T-lymphocytes
• Autologous Hematopoietic Stem Cell Transplantation
• Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Trial Overview The trial is testing genetically modified T-cells targeting CD19 on cancer cells plus a CMV vaccine after stem cell transplantation. The aim is to see if this combination helps prevent the return of high-grade B-cell non-Hodgkin lymphoma after transplant.

How Is the Trial Designed?

Group I: Treatment (CMV-specific CD19-CAR T cells, triplex vaccine) Experimental Treatment 4 Interventions

CONDITIONING REGIMEN: Patients receive standard conditioning regimen (typically carmustine, etoposide, cytarabine, melphalan) beginning approximately on day -9 in the absence of disease progression or unacceptable toxicity. TRANSPLANTATION: Patients undergo autoHSCT on day -2. CAR T-CELLS AND VACCINATION: Patients receive CMV-specific CD19-CAR T cells IV on day 0 and CMV-MVA triplex vaccine IM on days 28 and 56 in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A 21-year-old male patient developed possible CMV pneumonia three months after receiving CAR-T cell therapy for relapsed B-ALL, highlighting the risk of late-phase viral reactivation in immunocompromised patients.

Despite initial improvement with antiviral treatment, the patient's condition worsened after stopping one of the medications, leading to respiratory failure and death, emphasizing the need for careful monitoring and management of viral infections post-CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Fatal cytomegalovirus pneumonia after CAR-T cell therapy in the long-term follow-up. Cheng, J., Huang, J., Cao, W., et al.[2023]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

Genetically engineered T cells that express a CD19-specific chimeric immunoreceptor can effectively target and eradicate B-lineage malignancies, showcasing a promising approach in cancer treatment.

Using these modified T cells can potentially avoid the complications of graft-versus-host disease (GVHD) associated with traditional donor-derived T cell therapies, enhancing the safety and efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. Cooper, LJ., Al-Kadhimi, Z., DiGiusto, D., et al.[2007]

Two patients who received CD19-targeted CAR T cell therapy developed lymphoma, highlighting a potential safety concern associated with this treatment.

This case raises important questions about the long-term effects and monitoring of patients undergoing CAR T cell therapy, particularly regarding the risk of secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unforeseen Development of Lymphoma Derived from piggyBac CAR T Cells. [2021]

A new clinical platform successfully generates CMV-CD19CAR T cells from healthy donors, achieving a high enrichment of CMV-specific T cells and a transduction efficiency of 27%, which is crucial for effective cancer treatment.

These CMV-CD19CAR T cells showed strong anti-tumor activity and maintained memory characteristics, indicating their potential for improved persistence and efficacy in treating B cell malignancies, with plans for a clinical trial in patients with non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-scale manufacturing and characterization of CMV-CD19CAR T cells. Wang, X., Urak, R., Walter, M., et al.[2022]

In a study involving 16 patients, treatment with polyclonal CMV-specific T-cell lines led to significant in-vivo expansion of these immune cells, effectively reconstituting viral immunity against CMV infection after transplantation.

The use of these T-cell lines was shown to be effective, as eight patients did not require antiviral drugs, and only two experienced subsequent reactivation of the virus, highlighting the potential of this therapy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Peggs, KS., Verfuerth, S., Pizzey, A., et al.[2023]

CMV infection is a major risk after allogeneic stem cell transplantation, but reconstituting CMV-specific T cell responses can help protect patients from developing CMV disease.

Two strategies to enhance T cell immunity against CMV include transferring selected CMV-specific T cells directly from the donor to the patient and expanding these T cells in vitro using antigen presenting cells, both of which aim to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMV-specific T cell therapy. Einsele, H., Kapp, M., Grigoleit, GU.[2007]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

Anti-CD19 CAR-T cell therapy successfully achieved a complete response in a patient with relapsed/refractory follicular lymphoma, demonstrating its efficacy in treating this type of lymphoma.

The therapy not only addressed the lymphoma but also allowed for subsequent curative treatment of gastric adenocarcinoma, indicating its potential for use in patients with multiple malignancies while maintaining a good quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. Liu, J., Cao, F., Li, Z., et al.[2022]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

Citations

1. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7575989/

Efficacy and safety of CD19 chimeric antigen receptor T cells ... Anti-CD19 CAR T-cell treatment is a new therapy for patients with relapsed and refractory B-cell lymphoma. Among the small sample size in this study, it ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-cd19-car-cmv-specific-t-lymphocytes

Clinical Trials Using Anti-CD19-CAR CMV-specific T- ... Review the clinical trials studying anti-cd19-car cmv-specific t-lymphocytes on this list and use the filters to refine the results by age and location.

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1404351/full

Late events after anti-CD19 CAR T-cell therapy for ... CART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1567576924006921

Rapid response in relapsed follicular lymphoma to novel ... CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8475363/

Development of CMV-CD19 bi-specific CAR T cells with post ... We discuss an advanced strategy that facilitates post-infusion in vivo boosting of CAR T cells via CMV vaccination, to mediate durable remission of B cell ...

7. nature.com nature.com/articles/s41421-023-00625-0

Safety and feasibility of anti-CD19 CAR T cells expressing ... In this study, we developed a novel CAR-T therapy for patients with R/R LBCL by engineering CD19-specific CAR-T cells to secrete IL-7 and CCL19 ...