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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy to help people with certain types of B-cell lymphoma, a kind of blood cancer, that have not responded to other treatments. The trial aims to determine the therapy's effectiveness and safety and to find the best dose with minimal side effects. It suits individuals who have dealt with these specific lymphomas and have not seen improvements with previous treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research shows that the 19(T2)28z1xx TRAC T cell therapy is being tested for safety in people with relapsed or hard-to-treat B-cell lymphoma. In earlier studies, patients who received this treatment showed promising results, with some experiencing long-lasting remission, meaning their cancer symptoms stayed away for a significant time.

The study aims to find the highest dose that causes only mild or few side effects. The therapy uses specially modified T cells (a type of immune cell) to find and destroy cancer cells by recognizing a protein called CD19 on their surface.

As an early-phase trial, the primary focus is on testing safety. While the treatment appears promising, researchers are still learning about any possible side effects. Participants might experience side effects as researchers work to find the safest dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 19(T2)28z1xx TRAC T cell therapy because it uses a cutting-edge approach called CAR T-cell therapy, which is different from traditional treatments like chemotherapy or targeted therapy for Non-Hodgkin's Lymphoma. This treatment works by genetically modifying the patient's own T-cells to better recognize and attack cancer cells, offering a personalized approach to treatment. By directly harnessing the power of the immune system, this therapy has the potential to provide more effective and longer-lasting results, especially for those with difficult-to-treat forms of lymphoma like Diffuse Large B-Cell Lymphoma.

What evidence suggests that this treatment might be an effective treatment for B-cell lymphoma?

Research has shown that 19(T2)28z1xx TRAC CAR T-cell therapy yields promising results for individuals with B-cell lymphoma that has recurred or resisted other treatments. In this trial, participants with Diffuse Large B-Cell Lymphoma (DLBCL) and large B cell lymphoma will receive escalating doses of this modified T-cell therapy. Patients in previous studies experienced long-lasting remission, with cancer symptoms remaining absent for extended periods. This treatment modifies a person's own T cells (a type of immune cell) to enhance their ability to locate and attack cancer cells. Early trials suggest it could be effective, particularly for those who haven't succeeded with other treatments. Although more research is necessary, the initial results offer hope for people with this type of lymphoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05757700

NCT05757700 | Study of 19(T2)28z1xx TRAC-Chimeric ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11247921/

Calibrated CAR Signaling Enables Low-Dose Therapy in ... Here we report the first-in-human, phase 1 clinical trial of 19(T2)28z-1XX CAR T cells in relapsed/refractory large B-cell lymphoma. We hypothesized that 1XX ...

3. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00508-4

Novel CAR T-cell therapies for relapsed/refractory B-cell ... Patients with R/R diffuse large B-cell lymphomas (DLBCL) receiving 19(T2)28z1XX CAR T-cell therapy showed persistent remission, with an overall ...

4. researchgate.net researchgate.net/publication/388530389_Results_From_First-in-Human_Phase_I_Study_of_a_Novel_CD19-1XX_Chimeric_Antigen_Receptor_With_Calibrated_Signaling_in_Large_B-Cell_Lymphoma

Results From First-in-Human Phase I Study of a Novel ... Chimeric antigen receptor T-cell (CAR T) therapy has shown promising efficacy in relapsed and refractory diffuse large B cell lymphoma (DLBCL).

5. withpower.com withpower.com/trial/car-t-cell-therapy-for-non-hodgkins-lymphoma-4c683

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

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04823

Genetically Engineered Cells (19(T2)28z1XX TRAC-CAR T ... The 19(T2)28z1XX TRAC-CAR T cells can recognize a protein called CD19, which is found on the surface of B-cell cancer cells, and destroy those cells.