CAR T-Cell Therapy for B-Cell Lymphoma

Not currently recruiting at 6 trial locations

Overseen By M. Lia Palomba, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active CNS disease, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 19(T2)28z1xx CAR T cells, a type of cell therapy, for individuals with certain types of B-cell lymphoma, a cancer affecting white blood cells. The main goal is to determine the treatment's safety and identify the dose with the fewest side effects. If successful, the trial will assess the treatment's effectiveness in fighting cancer. Individuals who have tried other treatments without success, such as those whose cancer returned or worsened within a year, might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for 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 team or your doctor.

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

Research has shown that 19(T2)28z1xx CAR T cells are generally safe for individuals with recurring or difficult-to-treat B-cell cancers. Previous studies reported no severe cases of cytokine release syndrome, a common reaction to CAR T-cell therapy. Only one participant experienced mild and short-lasting side effects. These findings suggest that the treatment is well-tolerated at various doses. This is encouraging for prospective trial participants, as it indicates the treatment has undergone safety testing in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 19(T2)28z1xx CAR T cells for B-cell lymphoma because this treatment uses a personalized approach that modifies a patient's own T cells to better recognize and attack cancer cells. Unlike the standard chemotherapy and antibody therapies, which broadly target fast-growing cells, CAR T-cell therapy specifically engineers T cells to express a chimeric antigen receptor (CAR) that targets a protein on the surface of B-cell lymphoma cells. This precision targeting potentially offers a more effective and longer-lasting response with fewer side effects, making it a promising option for patients who have not responded to traditional treatments.

What evidence suggests that 19(T2)28z1xx CAR T cells might be an effective treatment for B-cell lymphoma?

Research has shown that 19(T2)28z1xx CAR T cells, the treatment under study in this trial, may help treat B-cell cancers that have returned or are difficult to treat. In one study, these specially designed cells helped 61% of patients avoid cancer-related issues for at least a year. Additionally, about 14 patients showed no signs of cancer during this period. The treatment proved effective at different dose levels, and researchers found it generally safe with manageable side effects. These results suggest that 19(T2)28z1xx CAR T cells could be a promising option for patients with challenging B-cell cancers. ^{1 2 6 7 8}

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 with certain types of B-cell cancers that haven't responded to previous treatments, including specific lymphomas and leukemias. Participants must have measurable disease, adequate organ function, and agree to use effective contraception. Excluded are those with poor performance status, active CNS disease, recent heart issues or uncontrolled infections.

Inclusion Criteria

Your creatinine, bilirubin, AST, and ALT levels are within a certain range.

My oxygen levels are 92% or higher on room air.

My lymphoma has not responded well to previous treatments, including chemotherapy.

Exclusion Criteria

Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study

I do not have severe neurological disorders like epilepsy or major brain injuries.

I do not have any ongoing serious infections.

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 CAR T cells to establish the recommended Phase II dose (RP2D)

4 weeks

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular visits for response and progression evaluation

What Are the Treatments Tested in This Trial?

Interventions

• 19(T2)28z1xx CAR T cells

Trial Overview

The trial is testing the safety of a new therapy called 19(T2)28z1xx CAR T cells for relapsed/refractory B-cell cancers. It aims to find the highest dose with minimal side effects and will also assess if this treatment effectively combats participants' cancer.

How Is the Trial Designed?

Group I: 19(T2)28z1xx CAR T cells Experimental Treatment 1 Intervention

Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1XX CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10\^6, 50 x 10\^6, 100 x 10\^6 and 200 x 10\^6 CAR T cells and one de-escalation dose: 12.5 x 10\^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1.

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

In a study involving 9 patients with relapsed or refractory B cell non-Hodgkin's lymphoma, both CD28 and 4-1BB targeted CAR-T cells showed similar antitumor efficacy, achieving a complete response rate of 67% within 3 months.

However, the 4-1BB (BBz CAR-T) cells were better tolerated, with only mild adverse events, while the CD28 (28z CAR-T) cells caused severe side effects, leading to the discontinuation of further evaluation for that group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin's Lymphoma. Ying, Z., He, T., Wang, X., et al.[2020]

A new CAR T cell therapy targeting CD79b has been developed, which shows effective recognition and destruction of B-cell lymphoma cells, including those that have lost CD19 expression, addressing a common issue of disease relapse.

The study demonstrated that CAR T cells targeting CD79b can work alone or in combination with CD19 targeting, providing a promising strategy to prevent antigen escape in B-cell lymphomas, based on experiments with cell lines and patient-derived models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19. Ormhøj, M., Scarfò, I., Cabral, ML., et al.[2020]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

CD19-directed CAR T-cell therapy has significantly improved survival rates for patients with high-risk B-cell non-Hodgkin lymphoma, showcasing its efficacy as a treatment option.

The article highlights ongoing research into the toxicity risks associated with CAR T-cell therapy, as well as strategies to mitigate these risks and address challenges like treatment resistance and global access to this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular therapy in lymphoma. Sureda, A., Lugtenburg, PJ., Kersten, MJ., et al.[2023]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

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]

Chimeric antigen receptor (CAR) T-cell therapies have shown promising results in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma, offering complete and lasting clinical responses where traditional therapies have failed.

Four CD19-directed CAR T-cell therapies have been approved by the FDA for specific types of relapsed or refractory lymphomas, indicating a significant advancement in treatment options for these challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage? Kanwal, B.[2021]

The novel CD19-PD-1/CD28 chimeric antigen receptor (CAR) T-cell therapy showed improved T-cell proliferation and effectiveness in killing PD-L1+ B-cell lymphoma cells, demonstrating enhanced efficacy compared to standard CD19 CAR T cells.

In a phase Ib study involving 17 adult patients with refractory or relapsed B-cell lymphoma, 58.8% of patients achieved an objective response, with 41.2% reaching complete remission, and the treatment was well-tolerated with no severe side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1-positive B-Cell Lymphoma. Liu, H., Lei, W., Zhang, C., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

CD19-CAR T cell therapy is feasible and safe for treating children and young adults with refractory B-cell malignancies, with a maximum tolerated dose established at 1×10^6 CAR T cells per kg.

The treatment showed potent anti-leukaemic activity, with all toxicities being fully reversible, including severe cases of cytokine release syndrome in 14% of patients, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lee, DW., Kochenderfer, JN., Stetler-Stevenson, M., et al.[2022]

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]

In a study involving six B-cell lymphoma patients, second-generation chimeric antigen receptor (CAR)-T cells showed superior expansion and persistence compared to first-generation CAR-T cells, indicating improved potential for effective cancer treatment.

This research highlights the importance of CAR-T cell design, as the enhanced ability of second-generation CAR-T cells to home in on tumor sites may lead to better clinical outcomes for patients with lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing tumor-targeting chimeric antigen receptor T cells in B-cell lymphoma patients. Gandhi, M., Jones, K.[2011]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39883889/

Results From First-in-Human Phase I Study of a Novel CD19 ...

With the median follow-up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond ...

2.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/7138/527855/Optimizing-Therapeutic-Outcome-of-CD19-T2-28z1XX

Optimizing Therapeutic Outcome of CD19(T2)28z1XX ...

CD19(T2)28z1xx demonstrated promising efficacy profile across various dose levels and exposure ranges. Selection of the lowest dose (25 x 106 ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04464200

NCT04464200 | 19(T2)28z1xx Chimeric Antigen Receptor ...

The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with relapsed/refractory B-cell cancers. The researchers will try to ...

4.

ashpublications.org

ashpublications.org/blood/article/140/Supplement%201/403/487351/A-Phase-I-Study-of-CD19-Targeted-19-T2-28z1xx-CAR

A Phase I Study of CD19-Targeted 19(T2)28z1xx CAR T Cells ...

Conclusions: Treatment with 19(T2)28z1XX CAR T cells was shown to be safe. No severe CRS was observed and only 1 pt experienced transient grade ...

5.

ascopubs.org

ascopubs.org/doi/abs/10.1200/JCO-24-02424

Results From First-in-Human Phase I Study of a Novel ...

With the median follow‐up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond ...

6.

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 ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124099634

Optimizing Therapeutic Outcome of CD19(T2)28z1XX ...

CD19(T2)28z1xx demonstrated promising efficacy profile across various dose levels and exposure ranges. Selection of the lowest dose (25 x 106 ...

8.

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 ...