CLBR001 CAR-T for Non-Hodgkin's Lymphoma

Recruiting at 7 trial locations

Overseen By Travis Young, Ph.D

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Calibr, a division of Scripps Research

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

Compensation: Varies

Number of Visits: 3

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves monitoring patients who received a special cancer treatment using their own modified immune cells. These patients are followed for an extended period to check for safety and effectiveness. The treatment works by reprogramming the patient's immune cells to better fight cancer and has shown promising results.

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 study team or your doctor.

What data supports the effectiveness of the treatment CLBR001 CAR-T for Non-Hodgkin's Lymphoma?

Research shows that similar CAR-T cell therapies targeting CD20 have been effective in treating B-cell non-Hodgkin lymphoma, with a high response rate and some patients achieving complete remission. This suggests that CLBR001 CAR-T, which is also a CAR-T cell therapy, may have potential effectiveness for this condition. ^{1 2 3 4 5}

Is CLBR001 CAR-T therapy safe for humans?

CAR-T therapies, including those targeting CD19 like CLBR001, have shown some common side effects such as cytokine release syndrome (a reaction causing fever and low blood pressure) and neurologic toxicities (affecting the nervous system), but these are usually treatable and reversible. Studies have shown that these therapies are generally safe, with most side effects being manageable. ^{6 7 8 9 10}

How is the CLBR001 CAR-T treatment different from other treatments for non-Hodgkin's lymphoma?

CLBR001 CAR-T treatment is a type of immunotherapy that uses specially modified T cells to target and destroy cancer cells, offering a novel approach for patients with non-Hodgkin's lymphoma who have not responded to standard treatments. Unlike traditional chemotherapy, CAR-T therapy is personalized and involves reprogramming a patient's own immune cells to fight the cancer. ^{6 9 10 11 12}

Research Team

Carolyn M. Mulroney

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for patients who have received at least one dose of CLBR001 CAR-T cells for various types of B-cell lymphomas and leukemias. Participants must be able to give informed consent and follow the study's visit schedule and requirements.

Inclusion Criteria

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

I have received at least one dose of CLBR001 cells and have either finished or stopped the treatment early.

Exclusion Criteria

There are no specific exclusion criteria for this study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Long-term Follow-up

Participants are monitored for safety, immunogenicity, and efficacy after receiving CLBR001 CAR-T cells

15 years

Monitoring

Regular monitoring of CLBR001 CAR+ cells in blood, bone marrow, and/or tissue specimens

24 months

Visits at 3, 6, 9, 12, and 24 months

Treatment Details

Interventions

• CLBR001

Trial Overview The study follows up long-term with patients treated with genetically modified autologous CLBR001 CAR-T cells, possibly in combination with SWI019, to monitor ongoing effects after their initial treatment.

Participant Groups

Group I: CLBR001 treated patients Experimental Treatment 1 Intervention

Patients who have been administered with CLBR001

Who Is Running the Clinical Trial?

Calibr, a division of Scripps Research

Lead Sponsor

Trials

9

Recruited

400+

Findings from Research

In a phase IIa trial involving 11 patients with relapsed or refractory CD20+ B-cell lymphoma, the use of CAR-modified T cells (CART-20) resulted in an impressive overall response rate of 81.8%, with 6 complete remissions and 3 partial remissions, indicating strong efficacy.

The treatment was well-tolerated with no severe toxicity reported, and the median progression-free survival was over 6 months, suggesting that CART-20 is a promising option for patients with difficult-to-treat lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Zhang, WY., Wang, Y., Guo, YL., et al.[2021]

CAR-T therapy is an innovative treatment that modifies T cells to target and attack cancer cells, such as those found in large B cell lymphoma.

In this case, a patient treated with CAR-T therapy for lymphoma developed myocarditis, highlighting a potential safety concern associated with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. Lee, DH., Jain, M., Lazaryan, A., et al.[2023]

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]

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]

Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising efficacy in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), with complete response rates of 40-60% in pivotal trials, and some patients achieving long-term remission.

While CAR-T therapy can lead to significant toxicities such as cytokine release syndrome and neurologic issues, these are generally treatable and reversible, making CAR-T a viable option for patients with poor prognosis in these lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR-T therapy for malignant lymphoma]. Shimoyama, T.[2023]

In a phase I study involving 10 patients with refractory diffuse large B-cell lymphoma (DLBCL), the anti-CD19 CAR T cell therapy (C-CAR011) demonstrated a 50% overall response rate at 12 weeks, indicating promising efficacy for this treatment.

The therapy showed a favorable safety profile, with 90% of patients experiencing cytokine release syndrome but no severe (grade ⩾ 3) cases or neurotoxicity, suggesting it is a safe option for patients with heavily treated DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. Fan, L., Wang, L., Cao, L., 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]

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]

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]

In a study of 129 adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) treated with CD19-directed CAR T therapy, 95.4% were hospitalized during treatment, with a median hospital stay of 17 days, highlighting the intensive care required during this therapy.

The estimated 6-month risk of requiring subsequent treatment after CAR T was 36.2%, indicating a significant chance of treatment failure, and emphasizing the need for effective salvage therapies for DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. Jalbert, JJ., Wu, N., Chen, CI., et al.[2022]

Lisocabtagene maraleucel (liso-cel), a CAR T-cell therapy targeting CD-19, achieved a 73% objective response rate and a 53% complete remission rate in patients with large B-cell lymphoma who had undergone a median of 3 prior therapies.

In the second-line treatment setting, liso-cel demonstrated superior event-free survival compared to standard care, highlighting its potential as a significant option for patients with relapsed or refractory large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. Mohty, R., Moreno Vanegas, Y., Chavez, JC., et al.[2023]

References

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

Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. [2023]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. Japan pubmed.ncbi.nlm.nih.gov

[CAR-T therapy for malignant lymphoma]. [2023]

7. China pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese 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. England pubmed.ncbi.nlm.nih.gov

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Lisocabtagene maraleucel for relapsed or refractory large B-cell non-Hodgkin lymphoma. [2023]