ACE1831 Cell Therapy for B-Cell Lymphoma

Recruiting at 7 trial locations

Overseen By Stephanie Chien

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Acepodia Biotech, Inc.

Disqualifiers: CNS lymphoma, CNS disorder, infection, cardiovascular disease, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 month

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing ACE1831, a cell therapy made from healthy donors' immune cells, in patients with CD20-expressing Non-Hodgkin lymphoma. The therapy aims to use special immune cells to target and kill cancer cells with the CD20 marker. Rituximab, a monoclonal antibody targeting CD20, has been widely used in treating B-cell malignancies such as non-Hodgkin's lymphoma.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the ACE1831 treatment for B-Cell Lymphoma?

Research shows that ACE1831, which combines rituximab with gamma delta T cells, effectively kills B-cell lymphoma cells, even those resistant to rituximab alone. In animal studies, this treatment slowed tumor growth and increased survival without causing harm, suggesting it could be a promising option for patients with relapsed or hard-to-treat B-cell lymphoma. ^{1 2 3 4 5}

What safety data exists for ACE1831 Cell Therapy for B-Cell Lymphoma?

The safety data for similar CAR-T cell therapies, which ACE1831 may be related to, shows that common side effects include cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), each occurring in about 33% of patients. B-cell aplasia (loss of normal B cells) was also noted in 54% of cases, indicating potential risks associated with this type of treatment. ^{6 7 8 9 10}

How is the ACE1831 treatment different from other treatments for B-cell lymphoma?

ACE1831 is unique because it uses a novel technology to attach rituximab, a cancer-targeting antibody, to gamma delta T cells without genetic modification, making it an off-the-shelf treatment. This approach enhances the T cells' ability to attack B-cell lymphoma, including rituximab-resistant cells, and avoids the high costs and safety concerns associated with traditional CAR-T therapies. ^{1 2 4 11 12}

Eligibility Criteria

This trial is for adults with certain types of B-cell Non-Hodgkin's Lymphoma that have tried at least two other treatments without success. Participants should be relatively healthy, able to perform daily activities with ease (ECOG 0-1), and not have a history of central nervous system lymphoma or other significant health issues like active infections or severe heart disease.

Inclusion Criteria

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

Oxygen saturation via pulse oxygenation ≥ 92% at rest on room air

My B-cell NHL has not improved after 2 treatments.

Exclusion Criteria

I have been treated with a gene-modified therapy targeting CD20.

I currently have a serious infection.

I have HIV, active hepatitis B, or hepatitis C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a lymphodepleting regimen followed by escalating doses of ACE1831, with or without obinutuzumab

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in physical examination, lab tests, urinalysis, vital signs, and ECG results

1 year

Long-term follow-up

Participants are monitored for objective response rate and pharmacodynamics of ACE1831

2 years

Treatment Details

Interventions

• ACE1831

Trial Overview The study tests ACE1831, an experimental cell therapy made from donor T cells targeting CD20 in B-cell malignancies. It's given alongside standard drugs Cyclophosphamide, Fludarabine, and Obinutuzumab to see how safe it is and how well it works against the cancer.

Participant Groups

Group I: Treatment Group B (ACE1831 and obinutuzumab) Experimental Treatment 4 Interventions

ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.

Group II: Treatment Group A (ACE1831) Experimental Treatment 3 Interventions

ACE1831 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE1831.

ACE1831 is already approved in United States for the following indications:

Approved in United States as ACE1831 for:

• None approved yet; under investigation for CD20-expressing B-cell malignancies

Who Is Running the Clinical Trial?

Acepodia Biotech, Inc.

Lead Sponsor

Trials

3

Recruited

80+

Findings from Research

ACE1831, a novel therapy using rituximab-conjugated γδ2 T cells, demonstrated superior effectiveness against B-cell lymphoma, including rituximab-resistant cells, compared to non-conjugated γδ2 T cells.

In vivo studies showed that ACE1831 significantly inhibited tumor growth and improved survival in mice without causing toxicity, highlighting its potential as a safe and effective off-the-shelf treatment for relapsed/refractory B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma. Li, HK., Wu, TS., Kuo, YC., et al.[2023]

Despite improvements in treatment for B cell malignancies, nearly 50% of patients experience relapse, highlighting the need for more effective therapies.

γδ T cells show promise as a novel immunotherapy for B cell cancers due to their anti-tumoral properties and ability to be manipulated for targeted treatment, with various strategies being explored to enhance their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

γδ T cells in immunotherapies for B-cell malignancies. Rimailho, L., Faria, C., Domagala, M., et al.[2023]

V gamma 9 V delta 2 T cells, when expanded with Zoledronate and IL-2, can express CD16, allowing them to enhance the effectiveness of monoclonal antibodies like rituximab and trastuzumab in targeting tumor cells.

The combination of CD16(+) V gamma 9 V delta 2 T cells with these antibodies significantly increases cytotoxicity against resistant tumor cells, suggesting that this approach could improve clinical outcomes in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

V gamma 9 V delta 2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs--rituximab and trastuzumab. Tokuyama, H., Hagi, T., Mattarollo, SR., et al.[2020]

Combining activated γδ T cells with the monoclonal antibody obinutuzumab significantly enhances the ability to kill B-cell malignancies through antibody-dependent cell-mediated cytotoxicity (ADCC), outperforming other tested antibodies like rituximab and daratumumab.

The study shows that even a small number of CD16 γδ T cells can effectively mediate strong ADCC, and that high concentrations of immunoglobulins can actually enhance the lysis of target cells rather than inhibit it, suggesting a promising strategy for improving cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell-specific Stimulation and Therapeutic Monoclonal Antibodies. Hoeres, T., Pretscher, D., Holzmann, E., et al.[2020]

A patient with Richter transformation, who was resistant to multiple lines of immunochemotherapy, achieved complete remission after receiving a novel therapy combining haploidentical γδ T cells and the monoclonal antibody obinutuzumab.

This case suggests that γδ T cell therapy is a promising and safe treatment option for aggressive lymphomas, warranting further clinical trials to explore its efficacy in larger patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical γδ T Cells Induce Complete Remission in Chemorefractory B-cell Non-Hodgkin Lymphoma. Bold, A., Gaertner, J., Bott, A., et al.[2023]

In a phase II trial involving 21 patients with refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL), coadministration of anti-CD19 and anti-CD20 CAR-T cells resulted in an impressive objective response rate of 81%, with 52.4% achieving a complete response, indicating high efficacy of this combined therapy.

The treatment was associated with manageable toxicity, as 28.5% of patients experienced grade 3-4 cytokine release syndrome, and 9.5% had neurologic events, suggesting that while the therapy is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. Sang, W., Shi, M., Yang, J., et al.[2021]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

Transducing T cells with anti-CD19 or anti-CD38 chimeric antigen receptors (CARs) resulted in over 60% efficiency and strong cytotoxic effects against B-cell non-Hodgkin lymphoma (B-NHL) cells, indicating a promising strategy for targeted cancer immunotherapy.

The combination of CAR-expressing T cells with rituximab showed enhanced and persistent tumor-suppressing activity in xenografted mice for over 2 months, supporting the potential for clinical testing in aggressive or relapsed B-NHL cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma. Mihara, K., Yanagihara, K., Takigahira, M., et al.[2017]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CAR T-cell therapy has shown remarkable success in treating B-cell acute lymphoblastic leukemia by targeting the CD19 marker, which is present on most B-cell tumors.

The therapy is being explored for other B-cell malignancies, including chronic lymphocytic leukemia and various types of lymphoma, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Pegram, HJ., Smith, EL., Rafiq, S., et al.[2018]

In a study of 7 patients with primary cutaneous B-cell lymphoma who had relapsed after chemotherapy, the combination of intravenous rituximab and single-dose cyclophosphamide resulted in an impressive overall response rate of 85.7%, with 5 patients achieving complete remission.

The treatment was well tolerated, and after a median follow-up of 13 months, most patients remained disease-free for significant durations, indicating promising efficacy and safety for this approach in managing relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. Fierro, MT., Savoia, P., Quaglino, P., et al.[2019]

TRU-015, a compact single-chain immunotherapeutic targeting CD20, shows potent direct signaling and effective antitumor activity against B-cell lymphoma, outperforming traditional rituximab in certain aspects.

In nonhuman primates, TRU-015 demonstrated rapid and durable depletion of peripheral blood B cells, suggesting it could enhance CD20-directed therapy while minimizing unwanted complement activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD20-directed small modular immunopharmaceutical, TRU-015, depletes normal and malignant B cells. Hayden-Ledbetter, MS., Cerveny, CG., Espling, E., et al.[2015]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

γδ T cells in immunotherapies for B-cell malignancies. [2023]

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

V gamma 9 V delta 2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs--rituximab and trastuzumab. [2020]

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

Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell-specific Stimulation and Therapeutic Monoclonal Antibodies. [2020]

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

Haploidentical γδ T Cells Induce Complete Remission in Chemorefractory B-cell Non-Hodgkin Lymphoma. [2023]

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

Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma. [2017]

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

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]

10. England pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? [2018]

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

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. [2019]

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

CD20-directed small modular immunopharmaceutical, TRU-015, depletes normal and malignant B cells. [2015]