ACE1831 Cell Therapy for B-Cell Lymphoma

Recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called ACE1831 (Rituximab-conjugated gamma delta T cells) for individuals with specific types of B-cell lymphoma, a cancer affecting certain white blood cells that have a protein called CD20. Researchers aim to determine if ACE1831 is safe and effective, both alone and in combination with another drug, obinutuzumab. Individuals with Non-Hodgkin lymphoma that has not responded to at least two treatments might be suitable for this study. Participants must have at least one measurable tumor and should not have certain heart or nervous system issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ACE1831, a cell therapy for B-cell lymphoma, has promising safety results from early studies. In tests on mice, the treatment significantly slowed cancer growth without noticeable side effects, indicating potential safety in humans.

ACE1831 has effectively killed B-cell lymphoma cells, even those resistant to common treatments like rituximab, suggesting it works well without causing harm. Although limited safety data exists on using ACE1831 with obinutuzumab, researchers are carefully studying its effects.

As a Phase 1 study, this is the first time the treatment is being tested in humans, with the main focus on safety. Doctors are closely monitoring to ensure the treatment is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for B-cell lymphoma rely on chemotherapy and targeted therapies like rituximab. But ACE1831 works differently, targeting cancer cells using engineered immune cells. Researchers are excited about ACE1831 because it involves a novel method of using modified cells that can directly attack B-cell lymphoma. Additionally, in one treatment arm, ACE1831 is combined with obinutuzumab, potentially enhancing its effectiveness by using two different mechanisms to combat the cancer. This innovative approach could offer a new avenue for patients who have not responded well to existing treatments.

What evidence suggests that ACE1831 might be an effective treatment for B-cell lymphoma?

Research has shown that ACE1831, a ready-to-use therapy using gamma delta T-cells, has potential in fighting B-cell lymphoma, a type of cancer. In lab studies, ACE1831 effectively killed B-cell lymphoma cells, even those unresponsive to rituximab, a common treatment. Animal tests demonstrated that it significantly slowed tumor growth and extended survival. In this trial, participants in Treatment Group A will receive ACE1831 as a monotherapy, while those in Treatment Group B will receive ACE1831 combined with obinutuzumab. The combination might enhance effectiveness against these cancer cells. Although still early, these findings suggest ACE1831 could be a promising new option for treating this cancer. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7251/528600/A-Phase-1-Open-Label-Multicenter-Study-of

A Phase 1, Open-Label, Multicenter Study of Treatment with ... ACE1831 persistence was evaluated by flow cytometry analysis using anti-Vδ2 TCR (γδT marker) antibody recognizing both patients' γδT cells and ...

2. cgtlive.com cgtlive.com/view/first-patient-with-nhl-receives-t-cell-therapy-in-phase-1-trial

First Patient With NHL Receives γδ T-Cell Therapy in ... Acepodia has dosed the first patient in the phase 1 trial (NCT05653271) evaluating ACE1831 for the treatment of non-Hodgkin lymphoma (NHL).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571679/

A Novel Allogeneic Rituximab-Conjugated Gamma Delta T ... ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37835538/

A Novel Allogeneic Rituximab-Conjugated Gamma Delta T ... ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed ...

5. targetedonc.com targetedonc.com/view/study-of-potential-car-t-alternative-for-relapsed-refractory-b-cell-malignancies-commences

Study of Potential CAR T Alternative for Relapsed/ ... A phase 1 study is exploring gamma delta T-cell therapy for the first time in patients with relapsed or refractory B-cell malignancies.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05653271

Study Details | NCT05653271 | ACE1831 in Adult Subjects ... The ACE1831-001 study is an open-label, Phase I, first-in-human (FIH) study that aims to evaluate the safety and tolerability, pharmacokinetics and ...