T-Cell Therapy for Non-Hodgkin's Lymphoma
(STARLIGHT-1 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Estrella Biopharma, Inc.
Must be taking: Anti-CD20, Anthracyclines
Must not be taking: Systemic steroids, Calcineurin inhibitors
Disqualifiers: CNS pathology, Cardiac disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of an autologous T-cell therapy (EB103) and to determine the Recommended Phase II Dose (RP2D) in adult subjects (≥ 18 years of age) who have relapsed/refractory (R/R) B-cell NHL. The study will include a dose escalation phase followed by an expansion phase.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic immunosuppressants or have had a recent live vaccine, you may need to discuss this with the trial team.
What data supports the effectiveness of the treatment EB103, CD19-Redirected ARTEMIS T-Cell Therapy for Non-Hodgkin's Lymphoma?
CD19-directed T-cell therapies, similar to EB103, have shown success in treating various B-cell cancers, including non-Hodgkin's lymphoma, with some patients experiencing long-term remission. These therapies have been recognized by the FDA for their potential, and they work by targeting specific markers on cancer cells, helping the immune system fight the disease more effectively.12345
Is T-Cell Therapy for Non-Hodgkin's Lymphoma generally safe in humans?
T-Cell Therapy, specifically CD19 CAR T-cell therapy, has been tested in humans and generally shows a good safety profile, with some patients experiencing mild to moderate side effects like cytokine release syndrome (a reaction where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (nerve damage). These side effects are usually manageable with proper medical care, although rare severe cases have been reported.678910
How is the EB103 treatment different from other treatments for non-Hodgkin's lymphoma?
EB103, also known as CD19-Redirected ARTEMIS T-Cell Therapy, is unique because it uses modified T-cells to specifically target and attack cancer cells that express the CD19 protein, which is common in B-cell malignancies like non-Hodgkin's lymphoma. This approach is part of a broader category of treatments called CAR T-cell therapies, which have shown promise in achieving long-term remissions in some patients by redirecting the body's own immune cells to fight cancer.1341112
Research Team
PW
Pei Wang, PhD
Principal Investigator
Eureka Therapeutics Inc.
Eligibility Criteria
Adults over 18 with relapsed/refractory B-cell Non-Hodgkin's Lymphoma can join this trial. They should understand the risks and benefits, have good organ function, and an ECOG score of ≤2 (which means they are able to carry out daily activities). Prior treatments must be completed with stable side effects not worse than Grade 1.Inclusion Criteria
I am 18 years old or older.
I understand the study's risks and benefits and have signed the consent form.
My condition is relapsed or refractory B-cell non-Hodgkin's lymphoma.
See 6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
A traditional dose escalation model (3+3 design) will be used to determine the Recommended Phase II Dose (RP2D)
21 months
Expansion
Additional subjects will be enrolled to further confirm the safety profile of EB103 at the RP2D and evaluate preliminary efficacy
Up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
90 days
Treatment Details
Interventions
- EB103 (CAR T-cell Therapy)
Trial OverviewThe trial is testing EB103, a new T-cell therapy for those whose lymphoma has returned or didn't respond to treatment. It starts by finding the best dose and then checks how well it works in more people at that dose.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: EB103Experimental Treatment1 Intervention
Approximately six (6) subjects will be treated to determine the RP2D. At the designated RP2D, approximately fifteen (15) additional subjects will be treated.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, DavisSacramento, CA
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Who Is Running the Clinical Trial?
Estrella Biopharma, Inc.
Lead Sponsor
Trials
1
Patients Recruited
20+
Eureka Therapeutics Inc.
Industry Sponsor
Trials
12
Patients Recruited
160+
References
CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies. [2023]Adoptive cell immunotherapy is a novel tool in the fight against cancer. Serving both effector and memory functions for the immune system, T cells make an obvious candidate for adoptive cell immunotherapy. By modifying native T cells with a chimeric antigen receptor (CAR), these cells can theoretically be targeted against any extracellular antigen. To date, the best-studied and clinically validated CAR T cells recognize CD19, a cell surface molecule on B cells and B cell malignancies. These CD19-directed T cells have shown clinical utility in chronic lymphocytic leukemia, acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphomas, with some patients achieving long-term disease remissions after treatment. This review will briefly summarize the current data supporting the use of adoptively transferred CAR T cells for the treatment of CD19-positive malignancies. Given these exciting results, the Food and Drug Administration has granted a 'breakthrough' designation for several variations of CD19-directed CAR T cells for treatment of adult and pediatric relapsed/refractory ALL.
Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage? [2021]For years, patients with B-cell non-Hodgkin lymphoma (NHL) have been treated with traditional first-line therapies with a fairly acceptable outcome. However, some individuals with relapsed or resistant lymphoma do not respond to those treatments, including chemotherapy, immunotherapy, radiotherapy, and (or) autologous stem cell transplantation. Based on the acquired immunotherapy knowledge, T-cells genetically engineered with chimeric antigen receptors (CARs) seem to offer complete, enduring clinical responses to patients with refractory or relapsed lymphomas. Currently, four autologous CD19-directed CAR T-cell therapies have gained approval by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma, while further CAR T-cell immunotherapies have entered the clinical trials pipeline. This review aims to summarize the efficacy and safety of the FDA-approved CAR T-cell treatments for the relapsed or refractory lymphomas.
T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. [2023]Several key advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL) over the past two decades have strategically exploited B-cell lineage markers suitable for targeting by immunotherapies. First, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab to a range of standard therapies conferred remarkable outcomes improvements in diverse settings, perhaps most prominently an overall survival advantage in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Subsequently, multiple chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have revolutionized the treatment of relapsed/refractory (rel/ref) DLBCL and are active in other B-NHL subtypes as well. Most recently, the longstanding aspiration to exploit patients' endogenous T-cells to combat lymphoma has been achieved via T-cell redirecting therapies such as bispecific antibodies (BsAbs) that incorporate dual targeting of a T-cell antigen such as CD3 plus a B-cell antigen such as CD19 or CD20 expressed by the tumor. These novel agents have demonstrated impressive activity as monotherapies in patients with heavily pre-treated, rel/ref B-NHL of a variety of subtypes. Now, myriad clinical trials are exploring combinations of T-cell redirectors with targeted therapies, antibody-drug conjugates, conventional chemotherapy, and even new immunotherapies. Here, we highlight key landmarks in the development of T-cell redirecting therapies for the treatment of B-NHL, emerging evidence and lessons from recent clinical trials, and exciting new directions in this arena.
Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. [2022]CD19CAR T cells facilitate a transformational treatment in various relapsed and refractory aggressive B-lineage cancers. In general, encouraging response rates have been observed in B-lineage-derived non-Hodgkin's lymphomas treated with CD19CAR T cells. The major cause of death in heavily pretreated NHL patients is lymphoma progression and lymphoma recurrence. Inefficient CAR T cell therapy is the result of the limited potency of the CAR T cell product or is due to loss of the targeted antigen. Target antigen loss has been identified as the key factor that can be addressed stringently by dual- or multitargeted CAR T cell approaches. We have developed a versatile adapter CAR T cell technology (AdCAR) that allows multitargeting. Screening of three different B-lineage lymphoma cell lines has revealed distinct immune target profiles. Cancer-specific adapter molecule combinations may be utilized to prevent antigen immune escape. In general, CD19CAR T cells become non-functional in CD19 negative lymphoma subsets; however, AdCAR T cells can be redirected to alternative target antigens beyond CD19, such as CD20, CD22, CD79B, and ROR-1. The capability to flexibly shift CAR specificity by exchanging the adapter molecule's specificity broadens the application and significantly increases the anti-leukemic and anti-lymphoma activity. The clinical evaluation of AdCAR T cells in lymphoma as a new concept of CAR T cell immunotherapy may overcome treatment failure due to antigen immune escape in monotargeted conventional CAR T cell therapies.
Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. [2021]On July 1, 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to CTL019, the anti-CD19 chimeric antigen receptor T-cell therapy developed at the University of Pennsylvania. This is the first personalized cellular therapy for cancer to be so designated and occurred 25 years after the first publication describing genetic redirection of T cells to a surface antigen of choice. The peer-reviewed literature currently contains the outcomes of more than 100 patients treated on clinical trials of anti-CD19 redirected T cells, and preliminary results on many more patients have been presented. At last count almost 30 clinical trials targeting CD19 were actively recruiting patients in North America, Europe, and Asia. Patients with high-risk B-cell malignancies therefore represent the first beneficiaries of an exciting and potent new treatment modality that harnesses the power of the immune system as never before. A handful of trials are targeting non-CD19 hematological and solid malignancies and represent the vanguard of enormous preclinical efforts to develop CAR T-cell therapy beyond B-cell malignancies. In this review, we explain the concept of chimeric antigen receptor gene-modified T cells, describe the extant results in hematologic malignancies, and share our outlook on where this modality is likely to head in the near future.
Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.
CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lymphoma effect, overall survival in patients with NHL after HCT remains short. Therefore, novel treatment modalities are urgently needed. Chimeric antigen receptor (CAR)-T cells, a new class of cellular immunotherapy involving ex vivo genetic modification of T cells to incorporate an engineered CAR have been used in clinical trials. In the majority of studies, B cell malignancies treated with CD19 targeting CAR-T cells have been analyzed. Recently, results from 2 CD19 directed CAR-T cell trials with an increased follow-up of patients led to Food and Drug Administration and European Medicines Agency approval of tisagenlecleucel and axicabtagene ciloleucel. Common adverse events (AEs) include cytokine release syndrome and neurological toxicity, which may require admission to an intensive care unit, B cell aplasia and hemophagocytic lymphohistiocytosis. These AEs are manageable when treated by an appropriately trained team following established algorithm. In this review, we summarize the results of 3 large phase II CD19 CAR-T cell trials and focus on AEs. We also provide a perspective of ongoing activity in this field with the intend to improve the potency of this emerging novel therapy.
Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma. [2022]Treatment with CD19-directed (CAR) T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30% to 40% of patients treated with axicabtagene-ciloleucel (axi-cel), usually within the first 4 weeks after administration of the dose and usually responding well to steroids. We describe a case of progressive central neurotoxicity occurring 9 months after axi-cel infusion in a patient with r/r LBCL who had undergone a prior allogeneic hematopoietic cell transplant. Despite extensive systemic and intrathecal immunosuppression, neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T-cell DNA copy numbers and elevated levels of interleukin-1 (IL-1) and IL-6 were found in the cerebral spinal fluid as clinical symptoms emerged, and CAR T-cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected, devastating, late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.
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.
CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). [2020]Relapsed and chemotherapy-refractory B-cell acute lymphoblastic leukemia (B-ALL) remain significant causes of cancer-associated morbidity and mortality for children and adults. Development of new molecularly targeted treatment strategies for patients with high-risk B-ALL is thus a major preclinical and clinical priority. Adoptive cellular therapy with patient-derived human T cells genetically engineered to express CD19 redirected chimeric antigen receptors (CD19 CAR T cells) is one immunotherapeutic modality that has recently demonstrated remarkable efficacy in re-inducing remission in patients with multiply relapsed B-ALL. Investigative teams at several major cancer centers are currently conducting phase I clinical trials in children and/or adults with relapsed/refractory B-ALL to assess the safety and to identify the maximally tolerated dose of each group's CD19 CAR T-cell product. All groups have reported major clinical toxicities associated with CD19 CAR T-cell treatment, including cytokine release syndrome (CRS) and macrophage activation syndrome, neurologic dysfunction and aplasia of normal B lymphocytes, while CD19 CAR T cells persist in vivo. Toxicities have generally been transient or manageable with supportive care measures. Some patients with life-threatening CD19 CAR T-cell induced sequelae have received anti-cytokine receptor antibody treatment to diminish CRS symptoms and/or corticosteroids to terminate CAR T-cell proliferation. Remarkably, 67-90% of children and adults with B-ALL treated with CD19 CAR T cells in these trials have achieved morphologic leukemia remission with many patients also in molecular remission. The duration of CD19 CAR T cell persistence in vivo has varied appreciably among treated patients and likely reflects differences in the CD19 CAR constructs utilized at each institution. CD19-positive and CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients. Phase II trials to assess the efficacy of CD19 CAR T-cell immunotherapy in larger cohorts of patients with relapsed/refractory B-ALL are ongoing or planned.
CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]Cellular immunotherapy with CD19-directed chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for aggressive B-cell non-Hodgkin lymphoma (B-NHL). Three CAR T-cell therapies are commercially avai.
Adoptive T-cell therapy for Hodgkin lymphoma. [2022]Although CAR T-cell therapy is US Food and Drug Administration-approved for B-cell non-Hodgkin lymphomas, the development of adoptive immunotherapy for the treatment of classic Hodgkin lymphoma (cHL) has not accelerated at a similar pace. Adoptive T-cell therapy with Epstein-Barr virus-specific cytotoxic T lymphocytes and CD30 CAR T cells have demonstrated significant clinical responses in early clinical trials of patients with cHL. Additionally, CD19 and CD123 CAR T cells that target the immunosuppressive tumor microenvironment in cHL have also been investigated. Here we discuss the landscape of clinical trials of adoptive immunotherapy for patients with cHL with a view toward current challenges and novel strategies to improve the development of CAR T-cell therapy for cHL.