Genetically Modified T-cells for Non-Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents, Corticosteroids

Disqualifiers: Uncontrolled illness, Active infection, Brain metastases, Other malignancy, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose and side effects of using specially modified T-cells (Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells) to treat non-Hodgkin's lymphoma, a cancer affecting the lymphatic system. Researchers focus on patients whose disease has returned or worsened after previous treatments or who have high-risk disease in remission. The process involves chemotherapy and a stem cell transplant to prepare the body, followed by an infusion of modified T-cells to help the immune system attack cancer cells. Individuals with intermediate-grade B-cell non-Hodgkin's lymphoma, such as DLBCL or MCL, who have experienced recurrence or progression, might be suitable for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.

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

Research has shown that treatments using modified T-cells, such as CD19 CAR T-cell therapy, are generally safe. Some patients experience mild side effects, while serious issues remain rare. Specifically, this therapy is considered safe for patients with high-risk non-Hodgkin's Lymphoma.

The treatment aids the immune system in identifying and attacking cancer cells. Although research remains in the early stages, the treatment has shown promise without major safety concerns. It is well-tolerated, with only minor side effects reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about genetically modified T-cells for Non-Hodgkin's Lymphoma because these cells are engineered to specifically target cancer cells by recognizing the CD19 protein on their surface. Unlike traditional chemotherapy, which attacks both cancerous and healthy cells, these CAR T-cells act like guided missiles, honing in on the cancer cells while sparing the rest. Additionally, this treatment involves enriching T-cells to become long-lived memory cells (Tcm), potentially leading to prolonged protection against the lymphoma. This precision and potential for lasting remission are what make this approach stand out from existing therapies.

What evidence suggests that genetically modified T-cells could be an effective treatment for non-Hodgkin's lymphoma?

Research shows that specially modified T-cells can help treat non-Hodgkin's lymphoma. In this trial, participants will receive genetically modified T-cells following a stem cell transplant. Earlier studies demonstrated encouraging results for patients with B-cell non-Hodgkin lymphoma who received these T-cells post-transplant. These T-cells are designed to target and attack a protein called CD19 on cancer cells, aiding the immune system in recognizing and fighting the cancer. This method has been tested in similar conditions and has shown promise in reducing tumors. Early results suggest that this treatment could improve outcomes for patients with this type of lymphoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Elizabeth Budde

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent or high-risk non-Hodgkin lymphoma who are scheduled for a stem cell transplant and have certain levels of healthy stem cells available. They must be able to understand the study, agree to use contraception, and not have uncontrolled infections or other cancers. People can't join if they've had allergic reactions to similar drugs, active hepatitis B/C or HIV, brain metastases, previous transplants, steroid dependence, or active autoimmune diseases.

Inclusion Criteria

My biopsy was reviewed and confirmed to be a type of B-cell NHL like DLBCL.

I am scheduled for standard chemotherapy before my main treatment.

I have had a stem cell transplant using my own cells.

Exclusion Criteria

Failure to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II study

I do not have any uncontrolled illnesses or active infections, including hepatitis B or C, or HIV.

I am not currently on any experimental treatments or other cancer therapies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization and Conditioning

Patients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor, followed by a myeloablative conditioning regimen

7 days

In-patient stay

Stem Cell Transplantation

Hematopoietic stem cell transplantation is performed on day 0

1 day

In-patient stay

T-cell Infusion

Patients receive CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2 or 3, which may be delayed up to day 45 if the patient is not yet eligible

1-45 days

In-patient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Weekly for 1 month, monthly for 1 year, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells
• Autologous Hematopoietic Stem Cell Transplantation

Trial Overview The trial is testing genetically modified T-cells after a patient receives a stem cell transplant. The goal is to see how well these modified T-cells work in treating lymphoma by boosting the immune system's ability to fight cancer without causing harm to normal cells.

How Is the Trial Designed?

Group I: Treatment (genetically modified T cell infusion) Experimental Treatment 3 Interventions

Patients undergo mobilization for autologous stem cell collection with cytoreductive chemotherapy and filgrastim and/or plerixafor per current standard operating policies. Patients undergo myeloablative conditioning regimen per institutional standards beginning day -7 followed by hematopoietic stem cell transplantation on day 0. Patients receive CD19-CAR-specific/truncated EGFR lentiviral vector-transduced autologous T cells IV on day 2 or 3 (may be delayed up to day 45 if the patient is not yet eligible). Patients who experience disease progression and have not experienced DLTs at greater than or equal to 100 days post HSCT will be allowed to receive an optional second T cell infusion.

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 new Phase I clinical trial at MD Anderson Cancer Center is investigating the safety and feasibility of using autologous T cells modified to express a CD19-specific chimeric antigen receptor (CAR) in patients with high-risk B-lymphoid malignancies undergoing hematopoietic stem-cell transplantation (HSCT).

This approach combines cell and gene therapies, utilizing a nonviral gene transfer method to create tumor-specific T cells, which may enhance treatment efficacy while minimizing the toxicities associated with traditional chemotherapy and radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. Kebriaei, P., Huls, H., Jena, B., et al.[2021]

The FDA is currently investigating potential links between BCMA- and CD19-directed CAR T-cell therapies and the development of secondary cancers in patients, highlighting a safety concern.

Despite these concerns, both the FDA and hematologists emphasize that the life-saving benefits of these immunotherapies for treating blood cancers outweigh the risks associated with secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Investigating CAR-Related T-cell Malignancies. [2023]

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

CAR T cell therapy has become an important treatment for certain blood cancers, with three types of anti-CD19 CAR-T cells already approved for use in the Czech Republic, and more trials underway for targeting other cancer-specific antigens.

While the management of CAR-T cell therapy has improved, including updated guidelines for early toxicity, long-term follow-up is essential due to potential late toxicities, highlighting the need for ongoing research to enhance efficacy and reduce side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. Jana, M., Tomáš, J., Michal, K., et al.[2022]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01815749

Study Details | NCT01815749 | Genetically Modified T-cell ... This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating ...

2. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/autologous-cd19car-cd28-cd3zeta-egfrt-expressing-tcm-enriched-t-cells

autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing ... Upon intravenous administration, autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells are directed to CD19-expressing tumor cells, thereby ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11539471/

Advances in CAR-T therapy for central nervous system tumors This review examined the research progress of chimeric antigen receptor T-cell therapy in gliomas, medulloblastomas, and lymphohematopoietic tumors of the ...

4. withpower.com withpower.com/trial/phase-1-burkitt-lymphoma-9-2013-83c16

Genetically Modified T-cells for Non-Hodgkin's Lymphoma In a study, patients with B-cell non-Hodgkin lymphoma who received genetically modified T cells after stem cell transplantation showed promising results, with ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40836026/

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).

6. ashpublications.org ashpublications.org/blood/article/127/24/2980/35453/Phase-1-studies-of-central-memory-derived-CD19-CAR

Phase 1 studies of central memory–derived CD19 CAR T–cell ... Key Points. TCM-derived CD19 CAR T–cell therapy is safe for treatment of poor-risk NHL patients undergoing autologous HSCT.