CAR-T Cell Therapy for Non-Hodgkin's Lymphoma

(CERTAIN Trial)

Not currently recruiting at 3 trial locations

Overseen By Tessa Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tessa Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, HIV, HBV, HCV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new therapy called CD30.CAR-T, a type of CAR-T cell therapy, for individuals with certain types of Non-Hodgkin's Lymphoma that have not responded to other treatments. The main goal is to determine the therapy's safety and identify the optimal dose. Suitable candidates have CD30-positive Non-Hodgkin's Lymphoma, have tried other treatments without success, and have at least one measurable tumor. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking immunosuppressive drugs and chronic systemic corticosteroids before participating. If you are on these medications, you will need to discontinue them.

Is there any evidence suggesting that CD30.CAR-T is likely to be safe for humans?

Research has shown that CD30.CAR-T cell therapy is generally safe and effective for treating certain types of lymphoma. Patients with relapsed or resistant Hodgkin's Lymphoma, which is similar to Non-Hodgkin's Lymphoma, have tolerated this treatment well.

The therapy uses special immune cells called T cells, combined with antibodies, to fight cancer. Many patients have experienced high response rates, with their cancer shrinking or disappearing temporarily. While there are risks, the therapy has demonstrated promising safety results so far.

This trial is in its early stages (Phase 1), focusing primarily on safety and determining the best dose. Safety data is still being collected. However, existing studies provide a hopeful outlook for those considering participation in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, such as chemotherapy and immunotherapy, CD30.CAR-T cell therapy offers a novel approach by genetically modifying a patient's own T-cells to target and destroy cancer cells expressing the CD30 protein. This personalized therapy harnesses the body's immune system to fight cancer more precisely, potentially leading to fewer side effects compared to traditional therapies. Researchers are excited because CD30.CAR-T therapy could provide a more effective and targeted treatment option for patients with CD30-positive subtypes of Non-Hodgkin's Lymphoma, such as ALCL and DLBCL, which might not respond well to conventional therapies.

What evidence suggests that CD30.CAR-T might be an effective treatment for Non-Hodgkin's Lymphoma?

Research has shown that CAR-T cell therapy targeting CD30 holds promise for treating Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). Studies have found high success rates, with some patients experiencing long-lasting remission. This therapy uses specially modified T cells, part of the immune system, to locate and attack cancer cells with the CD30 protein. The goal is to generate a strong immune response against the cancer. In this trial, participants with CD30-positive Non-Hodgkin's Lymphoma subtypes will receive this therapy. Although researchers are still testing its effectiveness in Non-Hodgkin's Lymphoma, early results suggest it could offer similar benefits. ^{3 5 6 7 8}

Who Is on the Research Team?

Sairah Ahmed

Principal Investigator

MD Anderson

Are You a Good Fit for This Trial?

Adults aged 18-75 with certain types of Non-Hodgkin Lymphoma that have relapsed or are not responding to treatment can join. They should be relatively healthy, able to perform daily activities, and have a life expectancy over 12 weeks. People with severe kidney issues, low blood counts, significant liver problems, active bleeding disorders, poor lung function or those on strong immune-suppressing drugs cannot participate.

Inclusion Criteria

My cancer is one of the specified types of lymphoma.

My CD30-positive NHL cancer did not respond to standard treatments.

Signed Informed Consent Form

Exclusion Criteria

Total bilirubin > 1.5 x ULN (>2 x ULN for patients with Gilbert's syndrome)

You have previously received an experimental treatment called CD30.CAR-T.

HIV positive

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with Bendamustine and Fludarabine prior to CD30.CAR-T cell infusion

1-2 weeks

Treatment

CD30.CAR-T cells are infused once following lymphodepleting chemotherapy

1 day

Follow-up

Participants are monitored for safety, dose-limiting toxicities, and effectiveness after CD30.CAR-T infusion

5 years

What Are the Treatments Tested in This Trial?

Interventions

• CD30.CAR-T

Trial Overview The trial is testing a new therapy called CD30.CAR-T cells in patients whose lymphoma cells express the CD30 marker and who haven't responded well to other treatments. It's an early-phase study focusing on safety and what doses are safe without causing too many side effects.

How Is the Trial Designed?

Group I: CD30 positive NHL subtypes Experimental Treatment 1 Intervention

(ALCL, PTCL-NOS, ENKTCL, DLBCL-NOS, PMBCL) Dose Level 1 Dose Level 2 Dose Level 3

Who Is Running the Clinical Trial?

Tessa Therapeutics

Lead Sponsor

Trials

4

Recruited

460+

Published Research Related to This Trial

In a study of 38 classical Hodgkin's Lymphoma (cHL) specimens, only 5.2% of Reed-Sternberg cells expressed both CD19 and CD30, indicating a limited population eligible for combined CAR T-cell therapy.

A patient treated with low doses of anti-CD19 and CD30 CAR T-cells did not experience severe adverse events and achieved long-term progression-free survival, suggesting that this approach may be safe and effective for high-risk relapsing/refractory cHL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. Xue, Y., Lai, X., Li, R., et al.[2022]

In a multi-center phase II clinical trial involving 12 patients with relapsed/refractory CD30+ lymphoma, the combination of anti-CD30 CAR-T therapy and PD-1 inhibitors resulted in a high overall response rate of 91.7%, with 50% of patients achieving complete remission.

The treatment demonstrated minimal toxicity, with only 4 patients experiencing cytokine release syndrome, and no cases of CAR-T-related encephalopathy syndrome, indicating a favorable safety profile alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma. Sang, W., Wang, X., Geng, H., et al.[2022]

A 61-year-old male patient with intravascular large B-cell lymphoma and CNS involvement achieved complete remission after receiving CAR T-cell therapy following a conditioning regimen and autologous stem cell transplantation.

The treatment was associated with only mild side effects, specifically grade 1 cytokine release syndrome, and no serious adverse events like neurotoxicity or pseudoprogression, suggesting that CAR T-cell therapy can be safely administered to patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. Yagi, Y., Kanemasa, Y., Ohigashi, A., et al.[2022]

CAR T-cell therapy, particularly anti-CD19 CAR T cells, shows strong efficacy in treating resistant forms of B-cell lymphomas, achieving durable complete remissions lasting over 2 years in some patients with refractory diffuse large-B-cell lymphoma (DLBCL).

Despite their effectiveness, CAR T-cell therapies can lead to severe toxicities, such as cytokine-release syndrome and neurological issues, highlighting the need for careful management and ongoing research into safer CAR designs and treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. Brudno, JN., Kochenderfer, JN.[2022]

CD30-directed CAR-T cells show promise as a treatment for relapsed or refractory lymphomas, particularly classical Hodgkin lymphoma, with early clinical trials indicating minimal toxicity and some preliminary efficacy.

Enhancing the persistence and expansion of CAR-T cells is crucial for improving treatment outcomes, with ongoing research focusing on optimizing treatment regimens and combining therapies to boost effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of driving CD30-directed CAR-T cells to the clinic. Grover, NS., Savoldo, B.[2020]

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]

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.

Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-directed CAR T-cell therapy in B-cell NHL. Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]

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]

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 therapies have shown high response rates in treating relapsed and refractory large cell lymphomas, with some patients experiencing long-lasting benefits.

The review emphasizes the importance of patient selection and the need for strategies to prevent relapse, as well as ongoing research into new CAR T cell therapies and their mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dawn of Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma. Perica, K., Palomba, L., Brentjens, RJ.[2021]

Citations

1. 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02917083

Study Details | NCT02917083 | CD30 CAR T Cells, ... This research study combines two different ways of fighting disease: antibodies and T cells. T cells, also called T lymphocytes, are special infection-fighting ...

3. 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 ...

4. ashpublications.org ashpublications.org/ashclinicalnews/news/3401/Evaluating-CD30-Targeted-CAR-T-Cell-Therapy-in

Evaluating CD30-Targeted CAR T-Cell Therapy in Patients ... Targeting CD30 with CD30-directed CAR T cells offers the opportunity to rapidly generate tumor-specific T cells in all patients with HL or ALCL.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04526834

Phase 1 Study of Autologous CD30.CAR-T in Relapsed or ... Adult patients with relapsed or refractory CD30-positive Non-Hodgkin Lymphoma who have failed standard available therapies and who meet eligibility criteria ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39806291/

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 ...

7. 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.

8. ashpublications.org ashpublications.org/blood/article/145/16/1788/535236/HSP-CAR30-with-a-high-proportion-of-less

HSP-CAR30 with a high proportion of less-differentiated T ... HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30 + lymphoma.