CAR T Cell Therapy for Lymphoma

(RELY-30 Trial)

Recruiting at 1 trial location

Overseen By Carlos Ramos, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Investigational agents, Corticosteroids

Disqualifiers: HIV, Rapidly progressive disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 1 day

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for lymphoma, a cancer affecting the lymph glands, using a special type of immune cell called a T cell. Researchers are testing whether T cells modified to carry an antibody—a protein that can attach to and help destroy cancer cells—can better fight the cancer after patients undergo a specific type of chemotherapy. This approach aims to make T cells more effective at targeting and killing cancer cells. Individuals with relapsed or resistant forms of lymphoma and tumors with a specific marker (CD30) might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CD30 CAR T cells could aid in treating lymphoma. These specially modified immune cells are designed to better locate and attack cancer cells. Reports suggest that this treatment can yield positive results for some patients, with long-lasting remissions in certain cases.

However, some studies have identified significant side effects. Patients have experienced issues such as skin rashes and prolonged low blood cell counts, which can sometimes be severe. Despite these challenges, other evidence indicates that the therapy can be effective and is generally considered safe for treating certain types of lymphoma.

Considering these factors is crucial when deciding to join a clinical trial for this treatment. Discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, which often include chemotherapy, radiation, and targeted therapies, CD30 CAR T cell therapy offers a unique approach by engineering a patient's own immune cells to target and destroy cancer cells. This treatment uses chimeric antigen receptor (CAR) technology to modify T cells to specifically recognize and attack CD30, a protein found on the surface of certain lymphoma cells. Researchers are excited about this therapy because it has the potential to provide a more personalized and precise treatment option with fewer side effects compared to traditional therapies. Additionally, CAR T cell therapy may offer hope for patients who have not responded to other treatments, providing a potentially powerful new weapon in the fight against lymphoma.

What evidence suggests that CD30 CAR T Cells might be an effective treatment for lymphoma?

Research has shown that CD30 CAR T cells, which participants in this trial will receive, could be helpful in treating lymphoma. These special immune cells are designed to find and destroy cancer cells by recognizing a marker called CD30. Studies have demonstrated high success rates, with some patients experiencing long-lasting improvements. However, these T cells sometimes don't remain active long enough to continue fighting the cancer, which can limit their effectiveness. In this trial, participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine before the infusion of CD30 CAR T cells. This process might enhance the effectiveness of CD30 CAR T cells by providing more room for them to grow and attack the cancer. While these results are promising, more research is needed to understand their long-term effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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.

My tumor is CD30-positive.

Hgb ≥ 7.0 (may be a transfused value)

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CD30 CAR T Cells
• Cyclophosphamide
• Fludarabine

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.

How Is the Trial Designed?

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

Each patient will receive one infusion of CAR modified T cells. Unless post autologous transplant, patients will receive lymphodepleting chemotherapy as three daily doses of cyclophosphamide (Cy: 500mg/m2/day) together with fludarabine (Flu:30mg/m2/day) from 48 hours to 2 weeks before T cell infusion. Clofarabine (20 mg/m2/day) may be substituted for fludarabine.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10394544/

Patient-reported outcomes in CD30-directed CAR-T cells ... Chimeric antigen receptor (CAR)-T cells targeting CD30 have demonstrated high response rates with durable remissions observed in a subset of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11731380/

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... Safety and efficacy of anti-CD30 CAR-T cell therapy in relapsed/refractory classic Hodgkin lymphoma: a systematic review and meta-analysis.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02917083

Study Details | NCT02917083 | CD30 CAR T Cells, ... 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 ...

4. ashpublications.org ashpublications.org/blood/article-abstract/145/16/1788/535236/HSP-CAR30-with-a-high-proportion-of-less?redirectedFrom=fulltext

HSP-CAR30 with a high proportion of less-differentiated T ... CD30-directed chimeric antigen receptor T-cell therapy (CART30) has limited efficacy in relapsed or refractory patients with CD30+ lymphoma, ...

5. nature.com nature.com/articles/s41598-022-14523-0

The third-generation anti-CD30 CAR T-cells specifically ... CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL).

6. ashpublications.org ashpublications.org/bloodadvances/article/8/3/802/498655/Transient-responses-and-significant-toxicities-of

Transient responses and significant toxicities of anti-CD30 ... Anti-CD30 CAR T cells had low efficacy in patients with CD30-expressing lymphoma. Rashes and prolonged cytopenias were frequent and severe in some cases, ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT03049449

T Cells Expressing a Fully-Human Anti-CD30 Chimeric ... We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing ...

8. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-13400-5

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... Current evidence suggests that anti-CD30 CAR-T cell therapy is effective and safe in treating R/R cHL and is worth considering as a viable therapeutic option.