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

No longer recruiting at 3 trial locations

Overseen By Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Anti-CD79a therapy

Disqualifiers: CNS lymphoma, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called bbT369, a type of CAR T-cell therapy, for individuals with non-Hodgkin's lymphoma. The researchers aim to determine if this treatment is safe and effective for those whose cancer has returned or hasn't responded to other treatments. It specifically targets patients who have tried at least two previous treatments, including a stem cell transplant. Participants will be observed for up to 15 years to ensure long-term safety and effectiveness. This trial offers a valuable opportunity for those whose cancer persists despite other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the chance to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on investigational cellular therapy or certain immunosuppressive treatments, you may not be eligible. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 CAR T-cell therapy, including types like bbT369, generally has a manageable safety profile. In past studies, most side effects were controllable. Although specific information on bbT369 remains limited, CAR T-cell therapies have been widely studied. They often cause side effects like cytokine release syndrome (a strong immune response) and neurotoxicity (nerve damage), but these are usually treatable.

Since this trial is in an early phase, researchers are closely monitoring bbT369 for safety in humans. Early-phase trials typically involve fewer participants and focus on understanding the treatment's safety. There is still much to learn about how well people tolerate bbT369. However, the treatment is under study because earlier research suggested it might help patients with non-Hodgkin's lymphoma, a type of blood cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Non-Hodgkin's Lymphoma, like chemotherapy and radiation, aim to kill cancer cells but can also harm healthy cells. Unlike these standard options, bbT369 is unique because it uses CAR T-cell therapy, which involves reprogramming a patient's own immune cells to specifically target and destroy lymphoma cells. This targeted approach not only promises to be more precise, reducing collateral damage to healthy cells, but it also has the potential to provide long-lasting protection by training the immune system to recognize and fight cancer cells in the future. Researchers are excited about this treatment because it represents a significant shift towards more personalized and effective cancer therapies.

What evidence suggests that bbT369 might be an effective treatment for non-Hodgkin's lymphoma?

Research shows that CAR T-cell therapy holds promise for treating non-Hodgkin's lymphoma. Studies have found that 69% of patients with relapsed or hard-to-treat B-cell non-Hodgkin's lymphoma responded to this treatment, and 49% went into complete remission, with no signs of cancer detected. CAR T-cell therapy also benefits patients who have not succeeded with other treatments, such as bispecific antibodies. These treatments have improved patients' quality of life in various real-world situations. Overall, CAR T-cell therapy, including the investigational treatment bbT369 studied in this trial, offers hope for those with challenging cases of this lymphoma type. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with B-cell Non-Hodgkin's Lymphoma who have tried at least two prior treatments, including an anti-CD20 antibody and chemotherapy. They must have a measurable lesion and be in relatively good health (ECOG ≤ 2). Not eligible if they've had certain autoimmune diseases, allogeneic bone marrow transplant, previous CAR T cell therapy or specific organ damage.

Inclusion Criteria

I have been diagnosed with a specific type of B-cell non-Hodgkin lymphoma.

I can take care of myself and am up and about more than half of my waking hours.

My B cell NHL has not improved after a stem cell transplant or at least 2 treatments including anti-CD20 and anthracycline.

Exclusion Criteria

I have not taken strong medication for an autoimmune disease in the last 2 years.

My condition worsened within 6 weeks after receiving anti-CD19 CAR T cell therapy.

I had severe side effects from previous CAR T therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 involves dose escalation to determine the maximum tolerated dose (MTD) of bbT369

Varies

Treatment

Participants receive bbT369 treatment in an open label, single arm setting

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• bbT369

Trial Overview

The study tests bbT369, a dual targeting CAR T cell drug with gene editing on patients with relapsed/refractory B-cell NHL. It's to see how safe it is and how well it works. This early-phase trial will gradually increase doses to find the right balance between effectiveness and safety.

How Is the Trial Designed?

Group I: bbT369 Experimental Arm Experimental Treatment 1 Intervention

Open label, single arm treatment with bbT369

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

2seventy bio

Lead Sponsor

Trials

3

Recruited

110+

Published Research Related to This Trial

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

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]

In a study of 39 Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL), CAR-T therapy achieved a high complete remission rate of 92.3%, with a median overall survival of 14.0 months, indicating its efficacy as a treatment option.

The therapy was associated with a high incidence of cytokine release syndrome (97.4%) and other adverse events, with higher levels of bone marrow blasts predicting worse survival and increased risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients. Li, L., Liu, J., Xu, M., et al.[2022]

Dual-targeting CAR-T cell therapy shows promising efficacy in treating B cell malignancies, with a 77% overall response rate and 52% complete response rate in patients with B cell non-Hodgkin lymphoma (B-NHL), and a 92% complete response rate in patients with B cell acute lymphoblastic leukemia (B-ALL).

The therapy has a manageable safety profile, with grade ≥3 cytokine release syndrome occurring in 14% of B-NHL patients and 11% of B-ALL patients, indicating that while there are risks, the benefits may outweigh them for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis. Yu, M., Zhang, Q., Kong, F., et al.[2023]

CAR-based therapies for T-cell malignancies show promising clinical responses above 50%, but most studies have short follow-up periods, making long-term efficacy unclear.

Specific toxicities, such as cytokine release syndrome (CRS) and graft-versus-host disease (GvHD), are associated with CAR-T treatments, with CRS being more common in antiCD7 CAR-T cells, though generally mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. Polgárová, K., Otáhal, P., Šálek, C., et al.[2022]

Anti-CD19 CAR T-cell therapy has demonstrated significant clinical activity in treating B-cell non-Hodgkin lymphoma (NHL), with objective response rates ranging from 50-83% for relapsed diffuse large B-cell lymphoma (DLBCL), 83-93% for follicular lymphoma (FL), and 93% for mantle cell lymphoma (MCL).

This therapy represents a promising treatment option for patients with poor-risk refractory B-cell NHLs, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions. Chavez, JC., Yassine, F., Sandoval-Sus, J., et al.[2022]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

CAR-T cell therapy has shown promising results in treating patients with refractory or relapsed B-cell non-Hodgkin lymphoma (B-NHL), addressing a significant unmet medical need as many patients do not respond to existing therapies.

Experts from Brazil and the United States are collaborating to provide recommendations for the use of CAR-T cells in B-NHL, especially with the anticipated approval of this therapy in Brazil, which could greatly improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. III: anti-CD19 CAR-T cell therapy for patients with non-Hodgkin lymphoma. Alencar, AJ., Hirayama, AV., Clé, DV., et al.[2021]

CD19-directed CAR-T therapy has shown promising long-term results, achieving durable remissions in nearly 50% of patients with relapsed/refractory large B-cell lymphoma, significantly improving their prognosis compared to the previous median survival of about 6 months with standard treatments.

The success of CAR-T therapy in large B-cell lymphoma has led to its expansion into other types of lymphomas, such as mantle cell and follicular lymphoma, and ongoing development of new CAR-T platforms aimed at enhancing efficacy and reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indications and platforms for CAR-T therapy in lymphomas beyond DLBCL. Iqbal, M., Savani, BN., Hamadani, M.[2023]

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]

CAR-T cell therapy demonstrated a high overall response rate of 85.2% in 27 patients with relapsed/refractory B cell non-Hodgkin lymphoma, with a complete response rate of 63.0% after a median follow-up of 32 months.

While adverse reactions like cytokine release syndrome and myelosuppression were common, they were manageable, and patients achieving a complete response had significantly better long-term survival rates compared to those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy of CAR-T cell therapy for patients with relapsed/refractory B cell non-Hodgkin lymphoma. Fu, S., Hu, Y., Huang, H.[2022]

Cellular therapies, including CAR T cells and allogeneic stem cell transplantation, have shown significant effectiveness in treating aggressive non-Hodgkin lymphomas, particularly in patients with poor prognoses.

The article discusses the clinical approach to selecting patients for CD19-directed CAR T cell therapy, emphasizing its growing importance in lymphoma management and the potential of newer cell therapies to enhance immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with cells. Chong, EA., Porter, DL.[2023]

In a study comparing CD19-directed CAR T-cell treatment and allogeneic hematopoietic cell transplantation (alloHCT) for patients with multiply relapsed/refractory large B-cell lymphoma, CAR T-cell therapy showed a median overall survival of 475 days compared to 285 days for alloHCT, indicating a potential advantage in survival outcomes.

CAR T-cell treatment had significantly lower nonrelapse mortality (3% vs 21%) compared to alloHCT, suggesting it may be a safer option for patients, while overall outcomes were not inferior, supporting the use of CAR T cells as a preferred first-line cellular immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells or allogeneic transplantation as standard of care for advanced large B-cell lymphoma: an intent-to-treat comparison. Dreger, P., Dietrich, S., Schubert, ML., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov

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Efficacy and safety of second-generation CAR T-cell therapy ...

The present study conducted a meta-analysis that showed highly favorable outcomes [objective response rate (ORR): 69%; complete remission (CR): 49%] in B-cell ...

3.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00070-7/fulltext

Treatment of non-Hodgkin lymphoma with point-of-care ...

After a median duration of follow up from CAR T-cell infusion of 24.5 months (IQR 17–32) among the event-free, 7 patients relapsed and 10 died.

4.

ashpublications.org

ashpublications.org/blood/article/140/Supplement%201/4639/488362/CAR-T-Cell-Therapy-Remain-Effective-in-Patients

CAR T-Cell Therapy Remain Effective in Patients with ...

CAR T-cell therapy remain effective in patients with relapse/refractory B-cell non-Hodgkin lymphoma after bispecific antibodies exposure.

5.

nature.com

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CAR-T cell therapy for cancer: current challenges and ...

2-targeted CAR has proven effective in treating gastrointestinal tumors in a study including 37 patients (NCT04196413), with an overall response ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS7580

CRC-403: A phase 1/2 study of bbT369, a dual targeting ...

Background: Although CD19 directed CAR T cell therapies have improved outcomes for non-Hodgkin's lymphoma (NHL) patients, only about 30-40% of ...

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withpower.com

withpower.com/trial/phase-2-lymphoma-non-hodgkin-2022-cadea

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

The safety data for CAR T-Cell Therapy, including variations like bbT369, shows that it generally has a manageable safety profile. In a study using Sleeping ...

8.

moffitt.org

moffitt.org/endeavor/archive/can-gene-edited-car-t-improve-non-hodgkin-lymphoma-outcomes/

Can Gene-Edited CAR T Improve Non-Hodgkin Lymphoma ...

While chimeric antigen receptor T-cell therapy, or CAR T, has improved outcomes for patients with non-Hodgkin lymphoma, only 30% to 40% of ...

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sec.gov/Archives/edgar/data/1860782/000186078222000011/ex991bbt369aacrpressrelease.htm

2seventy bio Presents New Preclinical Data on bbT369, ...

bbT369 outperformed CD19 CAR T cells in cell-based and mouse models, with increased IL-2 secretion and prolonged duration of tumor remission, ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11070555/

Novel and multiple targets for chimeric antigen receptor-based ...

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 in B-cell non-Hodgkin lymphoma (NHL) validates the utility of CAR-based therapy for lymphomatous ...