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

Overseen by Alex F. Herrera

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial studies the safety of using modified immune cells (CAR T-cells) and a special vaccine in patients with certain types of non-Hodgkin lymphoma who haven't responded well to initial treatments. The goal is to enhance the immune system to better target and kill cancer cells, potentially preventing the cancer from coming back. CAR T-cell therapy has shown promising results in treating blood cancers, including non-Hodgkin lymphoma.

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.

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

Research shows that CD19-specific CAR T-cells can lead to significant disease regression in B-cell malignancies, and CMV-specific T-cells can enhance immune responses after stem cell transplants. Combining these approaches, CMV-CD19CAR T-cells have shown better tumor control in animal models, suggesting potential effectiveness for Non-Hodgkin's Lymphoma. ^{1 2 3 4 5}

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

CAR T-cell therapy, including CD19 CAR-T cells, can cause serious side effects like infections and other toxic effects. There have been reports of severe complications, such as fatal pneumonia, in patients after receiving CAR-T cell therapy, especially in those with weakened immune systems. ^{2 3 6 7 8}

What makes the CAR T-Cells + CMV 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 vaccine that helps boost the immune response, potentially leading to better tumor control. The CMV-specific T-cells are designed to persist longer in the body, reducing the chance of cancer returning. ^{2 3 4 9 10}

Research Team

Alex F. Herrera

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Anti-CD19-CAR CMV-specific T-lymphocytes (CAR T-cell Therapy)
• Autologous Hematopoietic Stem Cell Transplantation (Procedure)
• Multi-peptide CMV-Modified Vaccinia Ankara Vaccine (Virus Therapy)

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.

Participant Groups

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+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

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.

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Large-scale manufacturing and characterization of CMV-CD19CAR T cells. [2022]

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

CMV-specific T cell therapy. [2007]

4. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

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

Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. [2007]

6. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Fatal cytomegalovirus pneumonia after CAR-T cell therapy in the long-term follow-up. [2023]

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

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

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

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

10. England 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. [2022]