CAR T-Cell Therapy for Non-Hodgkin's Lymphoma

Overseen By M. Lia Palomba, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active CNS disease, Impaired cardiac function, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 1 year

30 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment 19(T2)28z1xx TRAC T cell for Non-Hodgkin's Lymphoma?

Research shows that CAR T-cell therapy, which is a type of treatment that uses modified immune cells to target cancer, has been effective in treating aggressive B-cell non-Hodgkin lymphoma, especially in patients who do not respond to standard treatments. This therapy has been approved for use in relapsed or chemotherapy-resistant B-cell non-Hodgkin lymphoma, demonstrating its potential to induce complete and lasting responses. ^{1 2 3 4 5}

What makes the CAR T-cell treatment 19(T2)28z1xx TRAC T cell unique for non-Hodgkin's lymphoma?

CAR T-cell therapy is a novel treatment for non-Hodgkin's lymphoma that involves modifying a patient's own immune cells to better recognize and attack cancer cells. This approach is particularly promising for patients who do not respond to standard treatments, offering a new option for those with aggressive or resistant forms of the disease. ^{1 3 4 6 7}

What is the purpose of this trial?

The purpose of this research is to evaluate if study therapy, 19(T2)28z1xx TRAC-chimeric antigen receptor (CAR) T cells, may be an effective treatment for people with relapsed/refractory B-cell lymphoma. Researchers will also evaluate if this study therapy is safe, and to look for the highest dose that causes few or mild side effects in participants.

Research Team

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with certain types of B-cell lymphoma that haven't responded to or have returned after treatment, including chemotherapy. Participants must have adequate kidney, liver, and heart function, no active CNS disease or other cancers requiring therapy beyond observation or hormones (except skin cancer), and not be pregnant.

Inclusion Criteria

Patients need to have radiographically documented disease

My oxygen levels are 92% or higher without extra oxygen.

My cancer did not respond well to chemotherapy or returned within a year after treatment.

Exclusion Criteria

My condition limits me to minimal physical activity.

I have an active brain or spinal cord disease.

My heart's pumping ability is below normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of 19(T2)28z1xx TRAC-chimeric antigen receptor (CAR) T cells

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• 19(T2)28z1xx TRAC T cell

Trial Overview The trial is testing the safety and effectiveness of a new CAR T cell therapy called 19(T2)28z1xx TRAC for relapsed/refractory B-cell lymphoma. It aims to find the highest dose with minimal side effects by monitoring participants' responses.

Participant Groups

Group I: Participants with Diffuse Large B-Cell Lymphoma (DLBCL) and large B cell lymphoma Experimental Treatment 1 Intervention

Participants have histologically confirmed DLBCL and large B cell lymphoma. Participants will be treated with escalating doses of modified T cells.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

The study developed a CAR (CD4CAR) that enables CD8+ T cells to target and eliminate CD4+ T-cell lymphomas, showing effectiveness in both laboratory and patient-derived samples.

In mouse models of aggressive T-cell lymphoma, CD4CAR T cells not only suppressed tumor growth but also significantly extended survival, suggesting their potential as a new treatment option for patients with peripheral T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Pinz, K., Liu, H., Golightly, M., et al.[2018]

Approximately 20% of lymphoma patients develop resistance to conventional therapies, leading to a poor prognosis with a median survival of only 6.3 months, highlighting the need for effective new treatments.

T-cell immunotherapy, particularly CAR T-cell therapy targeting the CD19 antigen, has shown remarkable efficacy in inducing complete and durable responses in patients with chemotherapy-refractory B-cell non-Hodgkin lymphoma, and has been approved by the FDA for this use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of chimeric antigen receptor T cells in patients with non-Hodgkin lymphoma. Lulla, PD., Hill, LC., Ramos, CA., et al.[2021]

Adoptive therapy using CAR T-cells, specifically targeting CD19, represents a promising new treatment option for patients with high-risk B-cell non-Hodgkin's lymphomas, such as DLBCL and FL, who do not respond to standard therapies.

The review highlights the efficacy and toxicity profiles of CD19-directed CAR T-cell therapy, showing its potential as a viable alternative for patients with poor prognosis, supported by data from both early single-center studies and larger multicenter clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cell therapy for B-cell lymphomas. Chavez, JC., Locke, FL.[2020]

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

A 61-year-old male patient with intravascular large B-cell lymphoma and CNS involvement achieved complete remission after receiving CAR T-cell therapy following a conditioning regimen and autologous stem cell transplantation.

The treatment was associated with only mild side effects, specifically grade 1 cytokine release syndrome, and no serious adverse events like neurotoxicity or pseudoprogression, suggesting that CAR T-cell therapy can be safely administered to patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. Yagi, Y., Kanemasa, Y., Ohigashi, A., et al.[2022]

References

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

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. [2018]

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

The use of chimeric antigen receptor T cells in patients with non-Hodgkin lymphoma. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

CAR T cell therapy for B-cell lymphomas. [2020]

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

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. [2022]

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

Constant attack on T cell lymphomas. [2018]

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

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. [2022]