CAR T Cell Therapy for Lymphoma

(RELY-30 Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Carlos Ramos, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Baylor College of Medicine

Must not be taking: Investigational agents, Corticosteroids

Disqualifiers: HIV, Rapidly progressive disease, others

No Placebo Group

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any investigational agents or have received anti-CD30 antibody-based therapy recently. You also cannot use high-dose corticosteroids.

What data supports the effectiveness of the treatment CD30 CAR T Cells for lymphoma?

Research shows that CD30 CAR T-cell therapy can effectively target and eliminate CD30-positive lymphoma cells, including Hodgkin lymphoma, without harming healthy cells. This approach has shown promise in improving outcomes for patients with these types of lymphomas. ^{1 2 3 4 5}

Is CAR T Cell Therapy for Lymphoma safe for humans?

CAR T Cell Therapy, including CD30 CAR T cells, has shown effectiveness in treating lymphoma but can cause side effects like cytokine release syndrome (CRS) and immune-related issues. However, studies suggest that CD30 CAR T cells may have a better safety profile, as they do not harm healthy blood cells in the long term. ^{1 3 6 7 8}

How is CD30 CAR T Cell Therapy different from other treatments for lymphoma?

CD30 CAR T Cell Therapy is unique because it uses specially engineered T cells to target and destroy cancer cells expressing the CD30 protein, which is common in certain lymphomas. Unlike some other treatments, it does not harm healthy blood cells, making it a safer option for patients. ^{1 3 5 9 10}

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, tested in a certified lab.

Hgb ≥ 7.0 (may be a transfused value)

My tumor is CD30-positive.

Exclusion Criteria

I have severe heart disease that limits my daily activities.

I have not had anti-CD30 therapy in the last 4 weeks.

My tumor is located where it could block my airway if it grows.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive chemotherapy to decrease the level of circulating T cells prior to CD30.CAR T cells infusion

1 week

Treatment

Participants receive one injection of CD30.CAR T cells and are monitored for up to 3 hours post-injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood draws at specified intervals

15 years

Regular visits every 3 months for 1 year, every 6 months for 4 years, then yearly

Optional Extension

Participants with stable disease or reduction in lymphoma size may receive up to six additional doses of T cells at 8 to 12 weeks intervals

Variable

Treatment Details

Interventions

• CD30 CAR T Cells (CAR T-cell Therapy)
• Cyclophosphamide (Alkylating agents)
• Fludarabine (Anti-metabolites)

Trial Overview 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.

Participant Groups

Group I: CD30.CAR T Cells Experimental Treatment 1 Intervention

Each patient will receive one infusion of CAR modified T cells.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Texas Children's Hospital Houston, TX

Houston Methodist Hospital Houston, TX

Who Is Running the Clinical Trial?

Baylor College of Medicine Lead Sponsor

The Methodist Hospital Research Institute Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

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).

2. Australia pubmed.ncbi.nlm.nih.gov

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.

3. United States pubmed.ncbi.nlm.nih.gov

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.

4. Netherlands pubmed.ncbi.nlm.nih.gov

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.

5. England pubmed.ncbi.nlm.nih.gov

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.

6. Denmark pubmed.ncbi.nlm.nih.gov

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.

7. Switzerland pubmed.ncbi.nlm.nih.gov

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.

8. Switzerland pubmed.ncbi.nlm.nih.gov

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.

9. United States pubmed.ncbi.nlm.nih.gov

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.

10. Netherlands pubmed.ncbi.nlm.nih.gov

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.).