ACE1831 Cell Therapy for B-Cell Lymphoma
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Acepodia Biotech, Inc.
Disqualifiers: CNS lymphoma, CNS disorder, infection, cardiovascular disease, HIV, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
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.
12345What 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.
678910How 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.
1241112Eligibility 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.
+2 more
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.
+8 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Treatment Group B (ACE1831 and obinutuzumab)Experimental Treatment4 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 Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Indiana University Simon Comprehensive Cancer CenterIndianapolis, IN
The University of Texas MD Anderson Cancer CenterHouston, TX
Emory UniversityAtlanta, GA
Norton Cancer InstituteLouisville, KY
More Trial Locations
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Who Is Running the Clinical Trial?
Acepodia Biotech, Inc.Lead Sponsor
References
A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma. [2023]Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody-cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma. ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab conjugation. The in vivo xenograft study demonstrated that ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed toxicity. Mass spectrometry analysis indicated that cell activation receptors including the TCR complex, integrins and cytokine receptors were conjugated with rituximab. Intriguingly, the antigen recognition of the ACC-linked antibody/receptor complex stimulated NFAT activation and contributed to ACE1831-mediated cytotoxicity against CD20-expressing cancer cells. This study elucidates the role of the ACC-linked antibody/receptor complex in cytotoxicity and supports the potential of ACE1831 as an off-the-shelf γδ2 cell therapy against relapsed/refractory B-cell lymphoma.
γδ T cells in immunotherapies for B-cell malignancies. [2023]Despite the advancements in therapy for B cell malignancies and the increase in long-term survival of patients, almost half of them lead to relapse. Combinations of chemotherapy and monoclonal antibodies such as anti-CD20 leads to mixed outcomes. Recent developments in immune cell-based therapies are showing many encouraging results. γδ T cells, with their potential of functional plasticity and their anti-tumoral properties, emerged as good candidates for cancer immunotherapies. The representation and the diversity of γδ T cells in tissues and in the blood, in physiological conditions or in B-cell malignancies such as B cell lymphoma, chronic lymphoblastic leukemia or multiple myeloma, provides the possibility to manipulate them with immunotherapeutic approaches for these patients. In this review, we summarized several strategies based on the activation and tumor-targeting of γδ T cells, optimization of expansion protocols, and development of gene-modified γδ T cells, using combinations of antibodies and therapeutic drugs and adoptive cell therapy with autologous or allogenic γδ T cells following potential genetic modifications.
V gamma 9 V delta 2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs--rituximab and trastuzumab. [2020]V gamma 9 V delta 2 T cells exert potent cytotoxicity toward various tumor cells and adoptive transfer of V gamma 9 V delta 2 T cells is an attractive proposition for cell based immunotherapy. V gamma 9 V delta 2 T cells expanded in the presence of Zoledronate and IL-2 express CD16 (Fc gamma RIII), which raises the possibility that V gamma 9 V delta 2 T cells could be used in conjunction with tumor targeting monoclonal antibody drugs to increase antitumor cytotoxicity by antibody dependent cellular cytotoxicity (ADCC). Cytotoxic activity against CD20-positive B lineage lymphoma or chronic lymphocytic leukemia (CLL) and HER2-positive breast cancer cells was assessed in the presence of rituximab and trastuzumab, respectively. Cytotoxicity of V gamma 9 V delta 2 T cells against CD20-positive targets was higher when used in combination with rituximab. Similarly, V gamma 9 V delta 2 T cells used in combination with trastuzumab resulted in greater cytotoxicity against HER2-positive cells in comparison with either agent alone and this effect was restricted to the CD16(+)V gamma 9 V delta 2 T cell population. Our results show that CD16(+)V gamma 9 V delta 2 T cells recognize monoclonal antibody coated tumor cells via CD16 and exert ADCC similar to that observed with NK cells, even when target cells are relatively resistant to monoclonal antibodies or V gamma 9 V delta 2 T cells alone. Combination therapy involving ex vivo expanded CD16(+)V gamma 9 V delta 2 T cells and monoclonal antibodies may enhance the clinical outcomes for patients treated with monoclonal antibody therapy.
Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell-specific Stimulation and Therapeutic Monoclonal Antibodies. [2020]Tumor antigen-targeting monoclonal antibodies (mAbs) are an important element of current cancer therapies. Some of these therapeutic mAbs enable antibody-dependent cell mediated cytotoxicity (ADCC) against tumor cells. However, cancer-related functional impairment of immune effector cells may limit the clinical efficacy of antibody treatments. We reckoned that combining mAbs with cell-based immunotherapies would provide a clinically relevant synergism and benefit for cancer patients. Here, we focus on γδ T cells, as earlier studies demonstrated that γδ T-cell-based therapies are safe and promising for several types of malignancies. Similar to natural killer cells, their antitumor effects can be enhanced using antibodies, and they could, therefore, become a versatile effector cell platform for use with a variety of licensed therapeutic mAbs against cancer. In this study, we explore the potential of a combination therapy of activated γδ T cells with rituximab and the more recently developed mAbs (obinutuzumab and daratumumab) in different B-cell malignancies in vitro. Obinutuzumab outperformed the other mAbs with regard to direct target cell lysis and ADCC by γδ T cells in several CD20 cell lines and primary lymphoma specimens. We demonstrate that comparatively few CD16 γδ T cells are sufficient to mediate a strong ADCC. Using Fc-receptor-positive B-cell lymphomas as target cells, ADCC cannot be blocked by high concentrations of immunoglobulins or anti-CD16 antibodies, but both substances can promote cell mediated target cell lysis. This study expands on earlier reports on the therapeutic potential of distinctive tumor antigen-targeting mAbs and facilitates the understanding of the mechanism and potential of ADCC by γδ T-cell subsets.
Haploidentical γδ T Cells Induce Complete Remission in Chemorefractory B-cell Non-Hodgkin Lymphoma. [2023]The transformation of chronic lymphocytic leukemia to an aggressive lymphoma, called Richter transformation, is often accompanied by resistance to chemotherapy and high mortality. Thus, novel therapeutic strategies are required for the successful treatment of these patients. One possibility is cellular immunotherapy with chimeric antigen receptor T cells. However, the time delay until cells are available and the limited number of effector cells due to the impaired immune system of these patients potentially compromises the efficacy of this approach. Another promising attempt might be the therapy with γδ T cells. Once activated, they exhibit various antitumor effects against several types of malignancies. Furthermore, they can be safely used in an allogeneic setting and can be multiplied in vivo as already demonstrated in clinical studies. In vitro data, in addition, show that the cytotoxicity of γδ T cells can be significantly enhanced by monoclonal antibodies. Here we present a patient, who suffered from Richter transformation and did not respond to several lines of immunochemotherapy. Due to the lack of further therapy options, we conducted an individual therapy with adoptive transfer of haploidentical γδ T cells combined with the application of the monoclonal antibody obinutuzumab. A histologically confirmed complete remission was achieved through this therapy approach, whereby relevant side effects were not seen. This case highlights the potential of γδ T cells and the feasibility of this therapeutic approach for further clinical trials.
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]Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti-CD19 and anti-CD20 CAR-T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity.
Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. [2023]Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195). Major adverse events were cytokine release syndrome 33%, neurotoxicity 33% and B-cell aplasia 54%. Collectively, the results indicate encouraging response in relapsed/refractory B lymphoma and leukemia, especially in acute lymphoblastic leukemia (ALL) patients.
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]Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.
Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]Adoptive cellular immunotherapy with anti CD19 chimeric antigen receptor (CAR)-T cell has changed the treatment landscape in relapsed/refractory B cell lymphomas. They have emerged as effective therapy in patients with multiple relapsed/refractory disease, capable of sustaining durable remissions. Two CAR-T cell products (axicabtagene ciloleucel and tisagenlecleucel) are currently approved by the United States Food and Drug Administration. A third anti CD19 CAR-T cell, lisocabtagene ciloleucel is currently being evaluated in large clinical trials and may also be United States Food and Drug Administration-approved soon. CAR-T cell-related toxicities, including infections, cytokine release syndrome, and neurotoxicity are potential complications of therapy. With increasing use of CAR-T cells, the mechanism of toxicities and mitigation strategies needs to be developed. Additionally, reasons for CAR-T cell failure and progression following this therapy needs to be further studied. We describe the recent developments in this field, with emphasis on the complications of therapy and factors contributing to toxicities, efficacy, and resistance. We also describe the ongoing research in this field and the newer CAR-T cell constructs that are being developed to counter the challenges that have been identified in this field.
CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? [2018]Chimeric antigen receptor (CAR) T-cell therapy has recently come into the spotlight due to impressive results in patients with B-cell acute lymphoblastic leukemia. By targeting CD19, a marker expressed most B-cell tumors, as well as normal B cells, CAR T-cell therapy has been investigated as a treatment strategy for B-cell leukemia and lymphoma. This review will discuss the successes of this therapy for the treatment of B-cell acute lymphoblastic leukemia and the challenges to this therapeutic strategy. We will also discuss application of CAR T-cell therapy to chronic lymphocytic leukemia and other B-cell malignancies including a follicular lymphoma, diffuse large B-cell lymphoma, as well as acute and plasma cell malignancies.
Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. [2019]Rituximab, a chimeric antibody directed against CD20, has a high therapeutic value in refractory/relapsed low-grade or follicular B-cell non-Hodgkin's lymphomas as a monotherapy or in combination with polychemotherapy.
CD20-directed small modular immunopharmaceutical, TRU-015, depletes normal and malignant B cells. [2015]CD20-directed therapy with rituximab is effective in many patients with malignant lymphoma or follicular lymphoma. However, relapse frequently occurs within 1 year, and patients become increasingly refractory to retreatment. Our purpose was to produce a compact, single-chain CD20-targeting immunotherapeutic that could offer therapeutic advantages in the treatment of B-cell lymphoma.