Trial Summary
What is the purpose of this trial?The subject has a type of lymph gland cancer called Lymphoma.
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. 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 with germs. Both antibodies and T cells have been used to treat patients with cancers; they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together.
Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to test whether these genetically modified T cells given after chemotherapy will be more effective at killing cancer cells.
The gene that will be put into the T cells 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 receptor-activated T cells (CD30.CAR T cells) seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown.
Several studies suggest that the infused T cells need room to be able to multiply and grow to accomplish their functions, and that this may not happen if there are too many other T cells in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of circulating T cells prior to the CD30.CAR T cells infusion. This is called "lymphodepletion"
CD30.CAR T cells have previously been studied in lymphoma patients.
Is the treatment CD30 CAR T Cells a promising treatment for lymphoma?Yes, CD30 CAR T Cells are a promising treatment for lymphoma. They are designed to specifically target and destroy cancer cells in Hodgkin and non-Hodgkin lymphomas without harming healthy cells. This treatment has shown effectiveness in clinical trials and offers a new way to fight lymphoma by using the body's own immune cells.13489
What safety data is available for CAR T Cell Therapy for Lymphoma?CAR T Cell Therapy for Lymphoma, specifically targeting CD30, has shown effectiveness in treating Hodgkin lymphoma. However, it is associated with several adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity, which can lead to complications like infection or hemorrhage. CD30 CAR T cells have a superior therapeutic index as they do not attack healthy hematopoietic stem and progenitor cells, preserving normal blood cell levels. Ongoing research is focused on managing these adverse effects and optimizing safety.146710
What data supports the idea that CAR T Cell Therapy for Lymphoma is an effective treatment?The available research shows that CAR T Cell Therapy targeting CD30 has been effective in treating Hodgkin lymphoma. One study highlights that this therapy can specifically target and eliminate lymphoma cells without harming healthy cells, which is a significant advantage. Another study mentions that using a redesigned version of this therapy has shown improved results in fighting tumors. Additionally, combining CAR T Cell Therapy with other treatments, like immune checkpoint inhibitors, has shown promising results in enhancing its effectiveness. Overall, these studies suggest that CAR T Cell Therapy is a promising treatment for lymphoma, offering targeted action against cancer cells while sparing healthy ones.12459
Do I need to stop my current medications for the trial?The protocol does not specify if you need to stop your current medications. However, you cannot be on investigational agents, tumor vaccines, or systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of prednisone or higher. You also cannot have received anti-CD30 antibody-based therapy within the last 4 weeks.
Eligibility Criteria
This trial is for individuals aged 16-75 with relapsed/refractory Hodgkin's or Non-Hodgkin's Lymphoma, whose tumors express CD30 and have T cells available for modification. Participants must understand the consent form, have a certain level of physical fitness (Karnofsky/Lansky score >60%), stable organ function, no significant heart arrhythmias, not be pregnant or breastfeeding, and agree to use effective birth control.Inclusion Criteria
My tumor is CD30-positive.
My Hodgkin's or non-Hodgkin's lymphoma has come back or did not respond to treatment.
I am mostly able to care for myself but may need occasional help.
My T cells show at least 15% CD30CAR expression.
My lung function tests are at least half of what is expected for someone healthy.
I agree to use effective birth control during and 6 months after the study. I understand and have signed the informed consent.
My Hodgkin's or non-Hodgkin's lymphoma has returned or is not responding to treatment.
My kidney function is good.
Exclusion Criteria
I have severe heart disease that limits my daily activities.
My tumor is located where it could block my airway if it grows.
I am currently taking high doses of steroids.
My cancer has formed a large tumor or affects the area near my lungs.
I am currently experiencing bleeding when I urinate.
My cancer quickly worsened despite previous chemotherapy.
I currently have an active infection.
I currently have an active infection.
Treatment Details
The study tests genetically modified T cells called CD30.CAR T cells in patients who've had chemotherapy. These special T cells are designed to recognize and kill lymphoma cancer cells by targeting the CD30 molecule on their surface. The trial examines if these CAR T Cells can effectively fight cancer after reducing other circulating T cells through 'lymphodepletion' chemotherapy.
1Treatment groups
Experimental Treatment
Group I: CD30.CAR T CellsExperimental Treatment1 Intervention
Each patient will receive one infusion of CAR modified T cells.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Texas Children's HospitalHouston, TX
Houston Methodist HospitalHouston, TX
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Who is running the clinical trial?
Baylor College of MedicineLead Sponsor
The Methodist Hospital Research InstituteCollaborator
References
Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. [2018]Recent clinical trials with chimeric antigen receptor (CAR) redirected T cells targeting CD19 revealed particular efficacy in the treatment of leukemia/lymphoma, however, were accompanied by a lasting depletion of healthy B cells. We here explored CD30 as an alternative target, which is validated in lymphoma therapy and expressed by a broad variety of Hodgkin's and non-Hodgkin's lymphomas. As a safty concern, however, CD30 is also expressed by lymphocytes and hematopoietic stem and progenitor cells (HSPCs) during activation. We revealed that HRS3scFv-derived CAR T cells are superior since they were not blocked by soluble CD30 and did not attack CD30(+) HSPCs while eliminating CD30(+) lymphoma cells. Consequently, normal hemato- and lymphopoiesis was not affected in the long-term in the humanized mouse; the number of blood B and T cells remained unchanged. We provide evidence that the CD30(+) HSPCs are protected against a CAR T-cell attack by substantially lower CD30 levels than lymphoma cells and higher levels of the granzyme B inactivating SP6/PI9 serine protease, which furthermore increased upon activation. Taken together, adoptive cell therapy with anti-CD30 CAR T cells displays a superior therapeutic index in the treatment of CD30(+) malignancies leaving healthy activated lymphocytes and HSPCs unaffected.
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.
Chimeric Antigen Receptor-Engineered T Cell Therapy in Lymphoma. [2020]Chimeric antigen receptor (CAR) T cells are a form of adoptive therapy employing autologous T cells engineered with an artificial receptor, able to recognize tumor antigens through an HLA-independent mechanism. We will review data on safety and efficacy outcomes with CAR T cell therapy in 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).
Memory stem T cells modified with a redesigned CD30-chimeric antigen receptor show an enhanced antitumor effect in Hodgkin lymphoma. [2022]Label="OBJECTIVES" NlmCategory="OBJECTIVE">Adoptive cell therapy (ACT) with mature T cells modified with a chimeric antigen receptor has demonstrated improved outcome for B-cell malignancies. However, its application for others such as Hodgkin lymphoma remains a clinical challenge. CD30 antigen, expressed in Hodgkin lymphoma cells, is absent in most healthy tissues, representing an ideal target of ACT for this disease. Despite that, efficacy of CD30-chimeric antigen receptor (CAR) T cells for Hodgkin lymphoma remains modest. Here, we have developed and tested a novel CD30-CAR T to improve efficacy of CD30-CAR therapy, using a targeting epitope within the non-cleavable part of CD30 receptor, and memory stem T cells (TSCM) to improve engraftment, persistence and antitumor activity.
Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma. [2022]Patients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable.
Double systemic cytokine release syndrome following sequential infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T cells after autologous hematopoietic stem cell transplantation for a central diffuse large B-cell lymphoma patient: A case report and literature review. [2023]Chimeric Antigen Receptor T cell(CAR T-cell) therapy has been a great success in relapsed/refractory acute B lymphoblastic leukemia and B-cell lymphoma. At the same time, there are also related adverse reactions, especially cytokine release syndrome(CRS) and immune effector cell associated neurotoxicity syndrome(ICANS). However, Double CRS caused by CRA T cells are very rare.
Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. [2023]Chimeric antigen receptor T cells (CAR-T) therapy is a novel therapeutic approach that modifies T cells to attack cancer cells, including lymphoma. We present a case of large B cell lymphoma with intracardiac involvement treated with CAR-T in a patient who later experienced myocarditis after CAR-T therapy. (Level of Difficulty: Advanced.).
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.