15 Participants Needed

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

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

Trial Summary

What is the purpose of this trial?

This phase I trial studies the safety and feasibility of cytomegalovirus (CMV) specific CD19-chimeric antigen receptor (CAR) T cells in combination with the CMV-modified vaccinia Ankara (MVA) triplex vaccine following lymphodepletion in treating patients with intermediate or high grade B-cell non-Hodgkin lymphoma (NHL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refectory). CAR T cells are a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added in the laboratory. The special receptor is called CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Vaccines such as CMV-MVA triplex are made from gene-modified viruses and may help the body build an effective immune response to kill cancer cells. Giving CMV-specific CD19-CAR T-cells plus the CMV-MVA triplex vaccine may help prevent the cancer from coming back.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude those using systemic steroids or chronic immunosuppressants. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment CAR T-Cells + CMV-MVA Triplex Vaccine for Non-Hodgkin's Lymphoma?

Research shows that combining CMV-specific T cells with CD19 CAR T cells can improve tumor control by enhancing the persistence and effectiveness of the T cells. Additionally, CMV-specific T cell therapy has been effective in restoring immunity in patients with CMV infections, suggesting potential benefits in boosting the immune response in cancer treatment.12345

Is the CAR T-Cells + CMV-MVA Triplex Vaccine treatment generally safe for humans?

CAR T-cell therapy, including those targeting CD19, can cause side effects such as infections, cytokine release syndrome (a severe immune reaction), and other organ-related toxicities. While these treatments can be effective, they come with risks that are still being studied, especially regarding long-term safety.16789

What makes the CAR T-Cells + CMV-MVA Triplex Vaccine treatment unique for Non-Hodgkin's Lymphoma?

This treatment is unique because it combines CAR T-cells, which are engineered to target cancer cells, with a CMV-MVA Triplex Vaccine that boosts the immune system's response to cytomegalovirus (CMV), potentially enhancing the effectiveness and persistence of the CAR T-cells in fighting lymphoma.110111213

Research Team

Dr. Leslie Popplewell, Atlanta ...

Leslie Popplewell, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults with relapsed or refractory B-cell non-Hodgkin lymphoma, who are CMV seropositive and have a life expectancy of at least 16 weeks. They must be in good physical condition (KPS >= 70), not pregnant, willing to use birth control, and without significant heart, liver or kidney issues. Excluded are those with active autoimmune disease on treatment, recent allogeneic stem cell transplant recipients, or anyone on investigational agents.

Inclusion Criteria

Alanine aminotransferase (ALT) < 2.5 x ULN
My cancer is confirmed to be a certain type of aggressive CD19+ cancer.
I have no allergies or adverse reactions to specific medical treatments or vaccines.
See 20 more

Exclusion Criteria

I am currently using steroids or immunosuppressant medications regularly.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents or cetuximab
I don't have any health issues that would prevent me from receiving chemotherapy or CAR T-cell therapy.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Leukapheresis

Patients undergo leukapheresis to collect T cells for modification

1 day
1 visit (in-person)

Lymphodepletion

Patients receive lymphodepleting chemotherapy as per standard of care

1 week
Daily visits (in-person)

Treatment

Patients receive CMV-specific CD19-CAR T cells intravenously and CMV-MVA triplex vaccine intramuscularly

8 weeks
3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years
Regular visits (in-person and virtual)

Treatment Details

Interventions

  • Anti-CD19-CAR CMV-specific T-lymphocytes
  • 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-based vaccine after chemotherapy that reduces immune cells (lymphodepletion). It aims to see if this combination can help the body's immune system fight the lymphoma more effectively.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (CMV-specific CD19-CAR T cells, triplex vaccine)Experimental Treatment10 Interventions
Patients undergo leukapheresis on day -30 and receive lymphodepleting chemotherapy on days -10 to -3 per SOC on study. Patients then 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 unacceptable toxicity on study. Patients also undergo x-ray during screening and on study, as well as PET, CT, MRI, blood sample collection, and bone marrow biopsy on study and during follow-up.

Find a Clinic Near You

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+

Findings from Research

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.
Large-scale manufacturing and characterization of CMV-CD19CAR T cells.Wang, X., Urak, R., Walter, M., et al.[2022]
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.
CMV-specific T cell therapy.Einsele, H., Kapp, M., Grigoleit, GU.[2007]
A new clinical-scale protocol was developed to generate CMV-specific T cells from a single 500-mL blood draw, allowing for a more efficient and less time-consuming method compared to traditional techniques that require live virus and leukapheresis.
The generated CMV-specific T cells effectively lysed CMV-infected cells and showed reduced alloreactivity, indicating that this method not only produces a high quantity of functional T cells but also minimizes the risk of unwanted immune responses in transplant recipients.
Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants.Rauser, G., Einsele, H., Sinzger, C., et al.[2022]

References

Large-scale manufacturing and characterization of CMV-CD19CAR T cells. [2022]
CMV-specific T cell therapy. [2007]
Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants. [2022]
Development of CMV-CD19 bi-specific CAR T cells with post-infusion in vivo boost using an anti-CMV vaccine. [2022]
Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently. [2023]
Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]
Complications after CD19+ CAR T-Cell Therapy. [2020]
K562-Derived Whole-Cell Vaccine Enhances Antitumor Responses of CAR-Redirected Virus-Specific Cytotoxic T Lymphocytes In Vivo. [2021]
Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial. [2023]
11.United Statespubmed.ncbi.nlm.nih.gov
CMV Triplex Vaccine to Enhance Adaptive NK and T-cell Reconstitution After Autologous Hematopoietic Cell Transplantation. [2023]
12.United Statespubmed.ncbi.nlm.nih.gov
Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis. [2023]
Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. [2022]