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

Recruiting at 3 trial locations

Overseen By Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 1/2 Study of bbT369, a dual targeting CAR T cell drug product with a gene edit, in Relapsed and/or Refractory B cell Non-Hodgkin's Lymphoma.

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.

What data supports the idea that CAR T-Cell Therapy for Non-Hodgkin's Lymphoma is an effective treatment?

The available research shows that CAR T-Cell Therapy is a promising treatment for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, meaning it works well for those who haven't responded to other treatments. One study found that patients who received CAR T-Cell Therapy had a longer median overall survival of 475 days compared to 285 days for those who underwent an alternative treatment called alloHCT. Additionally, after receiving CAR T-Cell Therapy, 68% of patients were still alive after 12 months, compared to 54% for those who had alloHCT. This suggests that CAR T-Cell Therapy can be more effective than some other treatments for this type of lymphoma. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment bbT369 for Non-Hodgkin's Lymphoma?

Research shows that CAR T-cell therapy, which includes treatments like bbT369, has been promising for patients with relapsed or refractory B-cell non-Hodgkin lymphoma, offering significant improvements in survival compared to other therapies. ^{1 2 3 4 5}

What safety data is available for 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 Beauty CD19 CAR T-cells, no serious adverse events were directly attributed to the treatment, with only mild cytokine release syndrome (CRS) and no neurotoxicity reported. Another study on a novel PD-1 armored anti-CD19 CAR T-cell reported grade ≥3 CRS and neurotoxicity in 11.1% of patients. A systematic review found that in B-NHL patients, grade ≥3 CRS occurred in 14% and neurotoxicity in 5% of cases. Overall, while some severe adverse events like CRS and neurotoxicity can occur, they are relatively infrequent, and the therapy is considered safe with proper management. ^{6 7 8 9 10}

Is CAR T-Cell Therapy safe for treating Non-Hodgkin's Lymphoma?

CAR T-Cell Therapy has shown a generally good safety profile in treating Non-Hodgkin's Lymphoma, with some patients experiencing mild to moderate cytokine release syndrome (a reaction that can cause fever and low blood pressure) and rare cases of neurotoxicity (nerve damage). Most studies report that serious side effects are uncommon, and the treatment is well-tolerated. ^{6 7 8 9 10}

Is the treatment bbT369 a promising treatment for Non-Hodgkin's Lymphoma?

Yes, bbT369, which is a type of CAR T-cell therapy, is a promising treatment for Non-Hodgkin's Lymphoma. CAR T-cell therapy has shown impressive results, especially for patients whose disease has returned or not responded to other treatments. It has changed the treatment landscape and offers hope for better outcomes. ^{1 2 11 12 13}

How is the treatment bbT369 different from other treatments for non-Hodgkin's lymphoma?

The treatment bbT369 is a type of CAR T-cell therapy, which is a novel approach that uses genetically modified immune cells to target and destroy cancer cells. This therapy is particularly promising for patients with relapsed or refractory non-Hodgkin's lymphoma, offering hope where other treatments have failed. ^{1 2 11 12 13}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Brazil 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions. [2022]

3. China pubmed.ncbi.nlm.nih.gov

Long-term efficacy of CAR-T cell therapy for patients with relapsed/refractory B cell non-Hodgkin lymphoma. [2022]

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

Immunotherapy with cells. [2023]

5. United States 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. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

7. England 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. [2022]

8. United States 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. [2021]

9. United States 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. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. [2022]

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

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

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

New Indications and platforms for CAR-T therapy in lymphomas beyond DLBCL. [2023]

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

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