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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched 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 75% of patients remaining progression-free at 1 year. This suggests that the treatment may help control the disease and prevent relapse. ^{1 2 3 4 5}

Is the genetically modified T-cell treatment for Non-Hodgkin's Lymphoma safe?

Studies show that genetically modified T-cell treatments, like CD19 CAR T-cell therapy, are generally safe in humans, with some patients experiencing mild side effects such as cytokine release syndrome (a reaction that can cause fever and low blood pressure) and neurotoxicity (nerve-related side effects). However, there is a potential risk of secondary cancers, and long-term follow-up is recommended to monitor for late toxicities. ^{1 4 6 7 8}

How is the treatment with genetically modified T-cells for Non-Hodgkin's Lymphoma different from other treatments?

This treatment is unique because it uses genetically modified T-cells that are engineered to specifically target cancer cells, offering a personalized approach that works differently from traditional chemotherapy or radiation. It combines cell and gene therapy to enhance the immune system's ability to fight cancer, which is a novel approach compared to standard treatments. ^{1 3 9 10 11}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of genetically modified T-cells following peripheral blood stem cell transplant in treating patients with recurrent or high-risk non-Hodgkin lymphoma. Giving chemotherapy before a stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect)

Research Team

Elizabeth Budde

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. United States 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. [2021]

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

Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies. [2018]

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

CARs and cancers: questions and answers. [2021]

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

Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. [2022]

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

Reprint of: Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies. [2016]

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

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

7. Czech Republic pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. [2022]

8. United States 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. [2022]

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

Recent advances in engineered T cell therapies targeting B cell malignancies. [2018]

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

Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. [2023]

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

Immunotherapy of cancer using systemically delivered gene-modified human T lymphocytes. [2014]