CLBR001 CAR-T for Non-Hodgkin's Lymphoma

Enrolling by invitation 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a treatment called CLBR001 for individuals with Non-Hodgkin's Lymphoma, a cancer affecting the lymphatic system. The researchers aim to assess the long-term effects of CLBR001 CAR-T cells, which are specially modified to fight cancer. This study suits those who have received at least one dose of the treatment and can commit to regular follow-up visits. Participants must understand and agree to the study requirements. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this innovative therapy.

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.

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

Research shows that CLBR001 CAR-T cell therapy is generally safe, with most side effects being manageable. Studies indicate that participants usually tolerate the treatment well, and any negative reactions are typically controlled. Although detailed data on this specific trial is not available, the treatment's progression to this stage suggests reasonable safety. As a Phase 1 trial, the primary goal is to confirm safety in humans, indicating that the treatment has already passed initial safety checks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for Non-Hodgkin's Lymphoma, which often include chemotherapy and radiation, CLBR001 is unique because it employs CAR-T cell therapy. This innovative approach involves modifying a patient’s own T-cells to better recognize and attack cancer cells, offering a targeted treatment that could be more effective and less toxic. Researchers are excited about CLBR001 because it represents a new mechanism of action, potentially providing a more personalized and precise option for patients who may not respond well to traditional therapies.

What evidence suggests that CLBR001 might be an effective treatment for Non-Hodgkin's Lymphoma?

Research has shown that CAR T-cell therapy, such as CLBR001, offers promising results for treating Non-Hodgkin's Lymphoma. In one study, CAR T-cell treatments achieved up to a 90% complete response rate in patients with similar blood cancers. Another study found that patients who received CAR T-cell therapy had a 64% chance of remaining cancer-free for at least 12 to 18 months. Additionally, CAR T-cell therapy has improved patients' quality of life in various countries. These findings suggest that CLBR001, which participants in this trial will receive, could be effective for Non-Hodgkin's Lymphoma, though more research is needed to confirm its specific effects. ^{1 6 7 8 9}

Who Is on the Research Team?

Carolyn M. Mulroney

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-lymphoma-6-2023-7a391

Tazemetostat + CAR T Therapy for Non-Hodgkin's ... Research shows that Tazemetostat has demonstrated promising results in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, especially those with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04450069

Study Details | NCT04450069 | CLBR001 and SWI019 in ... This first-in-human study will assess the safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum tolerated dose (MTD) or optimal ...

3. astctjournal.org astctjournal.org/article/S2666-6367(25)01462-9/fulltext

Patient-Reported Outcomes of CAR T-Cell Therapy in Non- ... This study demonstrates that CAR T-cell therapy improves overall HRQoL in NHL patients across different countries in the real-world setting.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8436585/

Chimeric antigen receptor (CAR) T‐cell therapy for people ... In one study, relapse‐free survival remained at a rate of 64% at both 12 and 18 months. The evidence is very uncertain about the effect of CAR T‐cell therapy on ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525001624004829

T cell-redirecting therapies in hematological malignancies CD19-targeted therapies have shown unprecedented efficacy, achieving up to 90% complete response (CR) rates in trials for B cell acute ...

6. withpower.com withpower.com/trial/phase-1-leukemia-lymphocytic-chronic-b-cell-2021-8d6cc

CLBR001 CAR-T for Non-Hodgkin's Lymphoma Studies have shown that these therapies are generally safe, with most side effects being manageable. Show more.

7. scripps.edu scripps.edu/news-and-events/press-room/2020/20201001-calibr-fda-cart-cell-cancer-therapy.html

FDA grants Fast Track designation to Calibr's 'switchable' ... The CAR-T cell therapy known as “CLBR001 + SWI019,” has begun enrolling subjects in a Phase 1 trial assessing the safety and tolerability of the ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38582666/

Safety and Toxicity Profiles of CAR T Cell Therapy in Non- ... Overall, this study serves as the first to delineate toxicity profiles associated with various available CAR T products. By better understanding associated ...

9. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT244/742315/Abstract-CT244-HR001-a-novel-CD19-targeted-CAR-T

Abstract CT244: HR001, a novel CD19-targeted CAR-T cell ... Patients with R/R NHL could benefit from the HR001 treatment with satisfactory objective response, durable remission, and favorable safety profile.