Overseen ByAnne Beaven, MD
Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: UNC Lineberger Comprehensive Cancer Center
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration.
In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.
The purpose of this research study is to establish a safe dose of ATLCAR.CD30 cells to infuse after lymphodepleting chemotherapy and to estimate the number patients whose cancer does not progress for two years after ATLCAR.CD30 administration. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on the patient's cancer.
Is CD30 CAR T-Cell Therapy a promising treatment for lymphoma?Yes, CD30 CAR T-Cell Therapy is a promising treatment for lymphoma. It targets a protein called CD30, which is found in many types of lymphoma, including Hodgkin lymphoma. Early studies show it can be effective and safe, with ongoing research expected to improve its success.1451011
What data supports the idea that CD30 CAR T-Cell Therapy for Lymphoma is an effective treatment?The available research shows that CD30 CAR T-Cell Therapy is effective for treating relapsed or refractory CD30+ lymphomas, including Hodgkin lymphoma. In one study, 11 out of 12 patients responded to the treatment, with 6 achieving complete remission, meaning their cancer was no longer detectable. Another study reported that 7 out of 18 patients experienced partial remission, where their cancer shrank but did not disappear completely. These results suggest that CD30 CAR T-Cell Therapy can be a promising option for patients who have not responded to other treatments. Additionally, combining this therapy with another treatment called anti-PD-1 improved its effectiveness, with 100% of patients in one group responding to the combination.13479
What safety data is available for CD30 CAR T-Cell Therapy for Lymphoma?CD30 CAR T-Cell Therapy has shown some safety concerns, including cytokine release syndrome (CRS) and neurotoxicity, although these are not as severe as in some other CAR T-cell therapies. In a phase II trial, CRS was observed in 4 out of 12 patients, with only one experiencing severe grade 3 CRS, which was managed with glucocorticoid and tocilizumab. No CAR-T-related encephalopathy syndrome was reported. The therapy is generally well-tolerated with minimal toxicities, and third-generation CAR T-cells have shown minor side effects. Additionally, CD30 CAR T-cells do not target CD30+ hematopoietic stem and progenitor cells, reducing the risk of 'on-target off-tumor' toxicity.267812
Do I need to stop my current medications for the trial?The trial protocol does not specify if you must stop all current medications. However, you cannot use systemic corticosteroids at doses ≥10 mg prednisone daily, strong inhibitors of CYP1A2, or have received certain treatments like investigational agents, tumor vaccines, or anti-CD30 antibody-based therapy within specific timeframes before the trial. It's best to discuss your current medications with the trial team to ensure eligibility.
Eligibility Criteria
This trial is for adults and children with certain types of lymphoma (HL and NHL) that have returned or resisted treatment. Participants must not be pregnant, should use birth control if applicable, cannot have severe infections like HIV/HCV/HTLV, no recent cancer vaccines or CD30 antibody therapy, and must have good organ function. They also shouldn't be on high-dose steroids or medications that interfere with the chemotherapy drug bendamustine.Inclusion Criteria
I can care for myself but may not be able to do active work or play.
I am either between 3 to 17 years old and weigh at least 10kg, or I am 18 years or older.
My blood, liver, and kidney functions meet the required levels.
My tumor is not located where it could block my airway if it grows.
I am not taking strong CYP1A2 inhibitors like fluvoxamine or ciprofloxacin.
I do not have any ongoing serious infections.
I have had hepatitis B but it hasn't reactivated since my initial test.
My liver, kidneys, and lungs are functioning well according to recent tests.
My blood counts, liver and kidney functions are within normal ranges, and I can breathe well on my own.
I haven't had any cancer treatment not required by the study before my second infusion.
My liver and kidney functions are within normal limits, and I can breathe well on my own.
I am not pregnant, or I am post-menopausal or have not started menstruating.
I am mostly able to care for myself and carry out daily activities.
My kidney function, measured by serum creatinine, is within the required range for my age and gender.
I can care for myself but may not be able to do active work or play.
Exclusion Criteria
My tumor is located where it could block my airway if it grows.
My tumor is located where it could block my airway if it grows.
I do not have an active, poorly controlled HIV, HTLV, or HCV infection.
I am not taking medications like fluvoxamine or ciprofloxacin that strongly affect drug metabolism.
I have not had anti-CD30 antibody therapy in the last 4 weeks.
Participant Groups
The study tests ATLCAR.CD30 cells in patients after chemotherapy to find a safe dose and see how well it prevents cancer progression over two years. These are T cells modified with a new gene to target CD30+ lymphoma cells more effectively by using a combination of antibodies and T cell mechanisms.
1Treatment groups
Experimental Treatment
Group I: ATLCAR.CD30 cellsExperimental Treatment1 Intervention
Phase Ib: In adults, and separately, in children, two doses will be investigated 1x10\^8 cells/m2 and 2x10\^8 cells/m\^2. The study team will run two independent dose-escalation sequences, one for adults and another one for children. The study team plans to use the 3+3 design and start with a low dose of 1x10\^8 cells/m2. If there are no DLT in first 3 patients, the study team will go up to the dose of 2 x 10\^8 cells/m2. If there is toxicity in 1/3 patients in the initial cohort, the study team would expand to enroll up to 6 patients. If there are dose limiting toxicities (DLT) at the dose of 2 x 10\^8 cells/m\^2, the study team will initially decrease the dose to an intermediate dose of 1.5 x 10\^8 cells/m\^.
Phase II: The study team planning to enroll 31 patients to contribute data. Sequential boundary will be used to monitor DLT rate.
ATLCAR.CD30 cells is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as CD30 CAR-T cells for:
- Relapsed or refractory classical Hodgkin lymphoma
🇪🇺 Approved in European Union as CD30 CAR-T cells for:
- Relapsed or refractory classical Hodgkin lymphoma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, NC
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Who is running the clinical trial?
UNC Lineberger Comprehensive Cancer CenterLead Sponsor
References
T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor (CAR). The CAR contains an antigen recognition part (originating from an antibody), a T-cell receptor transmembrane and cytoplasmic signalling part, and one or more co-stimulatory domains. While CAR T-cells can be directed against any tumour target, most experience thus far has been obtained with targeting of the B-cell antigen CD19 that is expressed by B-cell acute lymphocytic leukaemia, chronic lymphocytic leukaemia and other B-cell lymphomas. The first clinical results are promising, although there are profound differences in response between patients with different haematological malignancies. Treatment-related side effects have been observed that require specific management. This review will explain the mechanism of action, summarise the experience to date and point out future directions for this hopeful new addition to the therapeutic armamentarium in the treatment of lymphoproliferative B-cell malignancies.
Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? [2017]Label="INTRODUCTION" NlmCategory="BACKGROUND">Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such 'on-target off-tumor' toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Areas covered: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field. Expert commentary: Targeting an activation associated antigen which is transiently expressed by stem cells seems to be safe, like CAR T cells targeting CD30 spare CD30+ hematopoietic stem and progenitor cells while eliminating CD30+ lymphoma cells, whereas targeting lineage associated antigens which increase in expression during cell maturation, like folate receptor-β and CD123, is of risk to destruct tissue stem cells.
Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial. [2022]Purpose: Relapsed or refractory Hodgkin lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory Hodgkin lymphoma.Experimental Design: Patients with relapsed or refractory Hodgkin lymphoma received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative PCR (qPCR).Results: Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions and received a mean of 1.56 × 107 CAR-positive T cell per kg (SD, 0.25; range, 1.1-2.1) in total during infusion. CART-30 cell infusion was tolerated, with grade ≥3 toxicities occurring only in two of 18 patients. Of 18 patients, seven achieved partial remission and six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites and reduction of the expression of CD30 in tumors.Conclusions: CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment. Clin Cancer Res; 23(5); 1156-66. ©2016 AACR.
Challenges of driving CD30-directed CAR-T cells to the clinic. [2020]Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas. Preclinical studies with CD30-directed CAR-T cells support the feasibility of this approach. Recently, two clinical trials of CD30-directed CAR-T cells in relapsed/refractory CD30+ lymphomas, including Hodgkin lymphoma, have been reported with minimal toxicities noted and preliminary efficacy seen in a proportion of patients. However, improving the persistence and expansion of CAR-T cells is key to further enhancing the efficacy of this treatment approach. Future directions include optimizing the lymphodepletion regimen, enhancing migration to the tumor site, and combination with other immune regulators. Several ongoing and upcoming clinical trials of CD30-directed CAR-T cells are expected to further enhance this approach to treat patients with relapsed and refractory CD30+ lymphomas.
Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. [2022]Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL).
CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. [2022]In clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin's Lymphoma (cHL).
Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma. [2022]Anti-CD30 CAR-T is a potent candidate therapy for relapsed/refractory (r/r) CD30+ lymphomas with therapy limitations, and the efficacy needed to be further improved. Herein a multi-center phase II clinical trial (NCT03196830) of anti-CD30 CAR-T treatment combined with PD-1 inhibitor in r/r CD30+ lymphoma was conducted. After a lymphocyte-depleting chemotherapy with fludarabine and cyclophosphamide, 4 patients in cohort 1 and 3 patients in cohort 2 received 106/kg and 107/kg CAR-T cells, respectively, and 5 patients in cohort 3 received 107/kg CAR-T cells combined with anti-PD-1 antibody. The safety and the efficacy of CAR-T cell therapy were analyzed. Cytokine release syndrome (CRS) was observed in 4 of 12 patients, and only 1 patient (patient 9) experienced grade 3 CRS and was treated with glucocorticoid and tocilizumab. No CAR-T-related encephalopathy syndrome was observed. Only two patients in cohorts 2 and 3 experienced obviously high plasma levels of IL-6 and ferritin after CD30 CAR-T cell infusion. The overall response rate (ORR) was 91.7% (11/12), with 6 patients achieving complete remission (CR) (50%). In cohorts 1 and 2, 6 patients got a response (85.7%), with 2 patients achieving CR (28.6%). In cohort 3, 100% ORR and 80% CR were obtained in 5 patients without ≥3 grade CRS. With a median follow-up of 21.5 months (range: 3-50 months), the progression-free survival and the overall survival rates were 45 and 70%, respectively. Of the 11 patients who got a response after CAR-T therapy, 7 patients (63.6%) maintained their response until the end of follow-up. Three patients died last because of disease progression. Taken together, the combination of anti-PD-1 antibody showed an enhancement effect on CD30 CAR-T therapy in r/r CD30+ lymphoma patients with minimal toxicities.
The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. [2022]CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.
Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. [2022]Long-term outcome is unfavourable for relapsed/refractory (r/r) lymphoma patients who are resistant to salvage chemotherapy, even after subsequent autologous stem-cell transplantation (ASCT). Although anti-CD30 chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is relatively limited.
Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. [2023]The authors review the current use of chimeric antigen receptor (CAR)-transduced T cells (CAR-T) in Hodgkin lymphoma (HL) and T-cell lymphomas (TCL) and discuss the data on CD30-targeting CAR-T cells, which seem to be safe and effective in HL. In addition, the authors examine the use of CAR-T cells targeting CD30, CD5, or CD7 in TCL, while highlighting the unique challenges of their use in this subset of lymphomas. Furthermore, the authors present future directions and ongoing trials investigating the use of CAR-T cells in TCL and HL.
Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy.
Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective treatment in those with refractory or relapsed lymphoma. CD19 CAR-T cell therapy can cause direct and indirect toxic adverse effects and increased risk for infection. Infectious complications and optimal antimicrobial prophylaxis strategies are an ongoing area of investigation.