CRISPR CAR-T Cell Therapy for B-Cell Lymphoma

Recruiting at 36 trial locations

Overseen By Socorro Portella, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Caribou Biosciences, Inc.

Must not be taking: Corticosteroids

Disqualifiers: CNS lymphoma, Seizure disorder, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CB-010, a type of CAR-T cell therapy, for individuals with B-cell non-Hodgkin lymphoma, a blood cancer unresponsive to standard treatments. The study aims to assess the safety and effectiveness of this treatment in the body. Participants will receive CB-010 following a preparation step involving specific medications. This trial may suit those whose B-cell non-Hodgkin lymphoma has recurred or who have not found success with other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroid therapy or have a thyroid disorder not controlled with stable hormone replacement, you may not be eligible to participate.

Is there any evidence suggesting that CB-010 is likely to be safe for humans?

Research has shown that CB-010, a type of gene-edited cell therapy, has a manageable safety profile. While some side effects occur, they are usually mild and can be handled by medical teams. Studies have found that people with relapsed or hard-to-treat B-cell lymphoma (a type of blood cancer) tolerated CB-010 fairly well. Promising results have emerged regarding both safety and effectiveness, even for aggressive forms of this cancer.

In summary, although CB-010 remains under study, early findings suggest it could be a safe option for those with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CB-010 because it uses cutting-edge CRISPR technology to enhance CAR-T cell therapy for treating B-cell lymphoma. Unlike standard treatments like chemotherapy and radiation, which target cancer cells more broadly, CB-010 precisely modifies the patient's T-cells to better recognize and attack cancerous B-cells. This precision could potentially lead to more effective outcomes with fewer side effects. Additionally, CRISPR allows for more durable and persistent T-cell responses, which might improve long-term remission rates compared to existing therapies.

What evidence suggests that CB-010 might be an effective treatment for B-cell lymphoma?

Research has shown that CB-010, a new cell therapy, offers promising results for treating B-cell non-Hodgkin lymphoma, particularly when the cancer returns or resists other treatments. In this trial, participants will receive CB-010 after lymphodepletion. Earlier studies found that patients generally tolerated CB-010 well and considered it safe. More importantly, the treatment effectively reduced cancer, even in aggressive cases. This therapy specifically targets a protein called CD19 on the surface of cancerous cells, making it a focused and potentially strong treatment option. Overall, these early findings suggest that CB-010 could be a promising choice for people with hard-to-treat B-cell lymphomas. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory B cell non-Hodgkin lymphoma who've had standard treatments can join. They must be fairly healthy, able to perform daily activities (ECOG status 0 or 1), and have good organ function. Excluded are those needing steroids, with certain neurological or autoimmune diseases, previous anti-CD19 therapy, stem cell transplants, CNS lymphoma/malignancy, primary immunodeficiency, active thyroid disorders (except stable hypothyroidism), and other recent cancers.

Inclusion Criteria

My blood, kidney, liver, heart, and lung functions are all within normal ranges.

My non-Hodgkin lymphoma has returned or didn't respond after standard treatment.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had any other cancers in the last 2 years, except those fully treated or unlikely to come back.

Unwillingness to follow extended safety monitoring

You have a weakened immune system from a medical condition you were born with.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion with cyclophosphamide and fludarabine before receiving CB-010

1 week

Dose Escalation

Participants receive CB-010 in a dose-escalation format to determine the optimal dose

28 days

Multiple visits for monitoring

Expansion

Participants receive CB-010 at the determined optimal dose

Up to 12 months

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CB-010
• Cyclophosphamide
• Fludarabine

Trial Overview The ANTLER trial is testing CB-010 after a pre-treatment ('lymphodepletion') with fludarabine and cyclophosphamide in adults with advanced B cell non-Hodgkin lymphoma. It aims to assess the safety of this CRISPR-edited CAR-T therapy as well as its potential effectiveness and how the body processes it.

How Is the Trial Designed?

Group I: Expansion of CB-010 Experimental Treatment 3 Interventions

Patients with relapsed or refractory non-Hodgkin lymphoma will receive CB-010 following lymphodepletion.

Group II: Dose Escalation of CB-010 Experimental Treatment 3 Interventions

Patients with relapsed or refractory non-Hodgkin lymphoma will receive CB-010 following lymphodepletion.

CB-010 is already approved in United States for the following indications:

Approved in United States as CB-010 for:

• Relapsed/Refractory Large B Cell Lymphoma (LBCL)
• Relapsed/Refractory B Cell Non-Hodgkin Lymphoma (B-NHL)

Who Is Running the Clinical Trial?

Caribou Biosciences, Inc.

Lead Sponsor

Trials

5

Recruited

360+

Published Research Related to This Trial

CRISPR/Cas9 gene editing technology is a powerful tool that enhances immune cell therapy for treating lymphoid cancers, such as lymphoma and leukemia.

The review discusses both current and future applications of CRISPR/Cas9 in engineering immune cells, while also addressing challenges and optimizations needed for effective use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of CRISPR/Cas9 gene editing in cellular therapies for lymphoid malignancies. Mehravar, M., Roshandel, E., Salimi, M., et al.[2021]

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]

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 clinical trial involving 21 adults with relapsed/refractory B cell non-Hodgkin's lymphoma, the virus-free CAR-T cell therapy PD1-19bbz showed promising efficacy, with 18 out of 21 patients achieving complete response and a median progression-free survival of 19.5 months.

The treatment had a manageable safety profile, with no dose-limiting toxicities reported, although some patients experienced low-grade cytokine release syndrome and hematologic toxicities, indicating that PD1-19bbz could be a safer alternative to traditional CAR-T therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of CRISPR-based non-viral PD1 locus specifically integrated anti-CD19 CAR-T cells in patients with relapsed or refractory Non-Hodgkin's lymphoma: a first-in-human phase I study. Hu, Y., Zu, C., Zhang, M., et al.[2023]

CAR-T-cell therapy has shown significant promise in treating relapsed or refractory B-cell malignancies, such as B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia, by targeting specific antigens like CD19 and BCMA.

The review highlights both the efficacy and toxicity of CD19- and BCMA-targeted CAR-T-cell therapies, indicating that while these treatments can be effective, they also come with potential side effects that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data. Roex, G., Feys, T., Beguin, Y., et al.[2020]

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]

The study demonstrated that using CRISPR/Cas9 to knock out the TCR gene in ARI-0001 CAR-T cells can effectively disrupt the TCR without significantly altering the T cell phenotype, achieving over 80% efficiency.

While this method shows promise for creating allogeneic CAR-T cells with maintained anti-tumor activity, there are potential safety risks due to possible large deletions in the genome that require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. Maldonado-Pérez, N., Tristán-Manzano, M., Justicia-Lirio, P., 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]

In a study involving 3 patients with relapsed/refractory B-cell malignancies, the novel CD19-KIRS2/Dap12-BB CAR-T cells showed significant short-term efficacy, achieving complete remission in one patient with B-cell acute lymphoblastic leukemia and partial remission in two patients with non-Hodgkin's lymphoma.

While the treatment resulted in manageable adverse reactions, including cytokine release syndrome and hematologic issues, the overall survival rates were promising, with patients living 282, 430, and 338 days post-treatment, indicating potential but highlighting the need for further research on long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors]. Ji, SW., Hua, T., Wang, JJ., et al.[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]

Allogeneic CAR-T therapies, derived from healthy donors, offer a promising alternative to autologous CAR-Ts by providing ready-to-use products that are standardized and potentially more effective due to their ability to bypass the immunosuppressive tumor environment.

While allogeneic CARs show encouraging preliminary results in early-phase clinical trials, they require genomic editing to prevent complications like graft versus host disease (GvHD), highlighting the need for further research to ensure their safety and feasibility in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Chimeric Antigen Receptor Therapy in Lymphoma. Khurana, A., Lin, Y.[2022]

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]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7025

A CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy ... Conclusions: CB-010 showed a manageable safety profile and promising efficacy for treatment of pts with r/r B-NHL, including aggressive subtypes ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04637763

CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy ... CB010A is a study evaluating safety, emerging efficacy, pharmacokinetics and immunogenicity of CB-010 in adults with relapsed/refractory B cell non-Hodgkin ...

3. investor.cariboubio.com investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-reports-positive-clinical-data-dose

Release details The data set includes all 16 patients treated in dose escalation with CB-010, an allogeneic anti-CD19 CAR-T cell therapy being evaluated in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6466472/

CAR T-cell therapy for B-cell lymphomas: clinical trial results ... Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B ...

5. jrheum.org jrheum.org/content/52/Suppl_1/147.3

A PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF CB ... GALLOP is a Phase 1 clinical trial evaluating CB-010 in the treatment of LN and ERL, which has the potential to overcome key barriers to access to CAR-T cell ...

6. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

7. cariboubio.com cariboubio.com/file.cfm/67/docs/cb-010_antler_phase_1_data_poster_eha%202022.pdf

CB-010 ANTLER Phase 1 trial design In ANTLER Phase 1 study, CB-010, an allogeneic CD19-directed CAR-T cell therapy with a PD-1 KO, demonstrated promising preliminary safety and efficacy in ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39946666/

Allogeneic Chimeric Antigen Receptor T-Cell ... - PubMed - NIH Allogeneic CD19 CAR T cells demonstrated promising overall and durable CR rates with a manageable safety profile in CD19 CAR T-naïve patients with R/R LBCL.