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}

Research Team

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

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.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Paul Klotman

Baylor College of Medicine

Chief Executive Officer since 2010

MD, PhD

James Versalovic

Baylor College of Medicine

Chief Medical Officer since 2020

MD from Baylor College of Medicine

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Dr. John P. Cooke

The Methodist Hospital Research Institute

Chief Medical Officer since 2013

MD, PhD

Dr. Jenny Chang

The Methodist Hospital Research Institute

Chief Executive Officer

MBBChir from University of Cambridge, MHCM from Johns Hopkins University

Findings from Research

In a study involving 41 heavily pretreated patients with relapsed or refractory Hodgkin lymphoma, CD30-targeted CAR T-cell therapy demonstrated a high overall response rate of 72%, with 59% achieving complete responses after fludarabine-based lymphodepletion.

The therapy showed a favorable safety profile, with most adverse events being grade 3 or higher hematologic issues and only mild cytokine release syndrome observed, indicating that CAR T-cell therapy can be safely extended to treat Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. Ramos, CA., Grover, NS., Beaven, AW., et al.[2022]

The study developed a novel CD30-chimeric antigen receptor (CAR) T cell therapy using memory stem T cells (TSCM), which showed improved persistence and antitumor activity against Hodgkin lymphoma in mouse models.

CD30-CAR TSCM-like cells effectively eradicated Hodgkin lymphoma tumors in vivo, demonstrating a survival advantage and enhanced tumor infiltration compared to more differentiated CAR T cells.

NCBI (Pubmed)

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. Alvarez-Fernández, C., Escribà-Garcia, L., Caballero, AC., et al.[2022]

CAR T cells targeting CD30 show promise in treating lymphoma without depleting healthy B cells, as they do not attack CD30(+) hematopoietic stem and progenitor cells (HSPCs).

The study demonstrated that anti-CD30 CAR T cells maintain normal blood cell levels in humanized mice, indicating a safer therapeutic profile compared to CD19-targeting CAR T cells, which can lead to lasting depletion of healthy B cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. Hombach, AA., Görgens, A., Chmielewski, M., et al.[2018]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

In a study of 133 patients with relapsed or refractory lymphomas receiving CAR-T-cell therapy, severe cytopenias (neutropenia, anemia, and thrombocytopenia) were common, occurring in 71%, 30%, and 41% of patients, respectively, particularly in the early phase after treatment.

Severe cytopenias were linked to higher rates of infections and poorer survival outcomes, suggesting that better patient selection and management of cytokine release syndrome (CRS) could reduce these adverse effects and improve overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma. Zhou, J., Zhang, Y., Shan, M., et al.[2022]

This case report describes the first known instance of double cytokine release syndrome (CRS) occurring in a patient with secondary central diffuse large B-cell lymphoma after receiving sequential CAR T-cell therapy, highlighting the potential for severe adverse reactions even in successful treatments.

The patient's symptoms of double CRS were effectively managed with tocilizumab and glucocorticoids, leading to complete resolution of symptoms and a significant reduction in the lymphoma, demonstrating the importance of early detection and appropriate treatment strategies for CRS in CAR T-cell therapy.

NCBI (Pubmed)

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. Zheng, J., Xiao, Y., Wu, XQ., et al.[2023]

CAR T cell therapy targeting CD19 has shown high efficacy in treating relapsed or refractory aggressive B cell non-Hodgkin lymphoma, leading to durable remissions in many patients, as demonstrated in multicenter trials.

The most common side effects of this therapy include cytokine release syndrome and neurotoxicity, highlighting the need for ongoing research to improve safety and explore its use in earlier treatment stages and other types of B cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Engineered T Cell Therapy in Lymphoma. Strati, P., Neelapu, SS.[2020]

CAR-T therapy is an innovative treatment that modifies T cells to target and attack cancer cells, such as those found in large B cell lymphoma.

In this case, a patient treated with CAR-T therapy for lymphoma developed myocarditis, highlighting a potential safety concern associated with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. Lee, DH., Jain, M., Lazaryan, A., et al.[2023]

References

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

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. [2022]

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]

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]

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

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

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]

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

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

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

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma. [2022]

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]

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

Chimeric Antigen Receptor-Engineered T Cell Therapy in Lymphoma. [2020]

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

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. [2023]