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

(CERTAIN Trial)

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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1 study to evaluate safety and dose-limiting toxicity of autologous CD30.CAR-T in subjects with relapsed or refractory CD30+ Non-Hodgkin Lymphoma

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.

What data supports the effectiveness of the CD30.CAR-T treatment for Non-Hodgkin's Lymphoma?

CD30-directed CAR-T cell therapy has shown high response rates and durable remissions in patients with relapsed or refractory CD30+ lymphomas, including Hodgkin lymphoma, with minimal toxicities. Additionally, combining CD30 CAR-T therapy with anti-PD-1 antibodies has enhanced its effectiveness, achieving a 100% overall response rate in a small group of patients. ^{1 2 3 4 5}

Is CD30 CAR-T cell therapy generally safe for humans?

CD30 CAR-T cell therapy has shown low rates of toxicity, including mild cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and no neurotoxicity (nerve damage) in some studies. Patient-reported outcomes indicate that physical function and symptom burden return to baseline levels within a month after treatment, suggesting a favorable safety profile. ^{1 3 6 7 8}

How is CD30.CAR-T treatment different from other treatments for non-Hodgkin's lymphoma?

CD30.CAR-T treatment is unique because it uses specially modified immune cells (CAR-T cells) to target the CD30 protein found on certain lymphoma cells, which is not present in most healthy tissues. This approach is promising for types of lymphoma that do not express the CD19 protein, which is the target of other CAR-T therapies. ^{2 4 9 10 11}

Research Team

Sairah Ahmed

Principal Investigator

MD Anderson

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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, 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in CD30-directed CAR-T cells against relapsed/refractory CD30+ lymphomas. [2023]

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. Switzerland 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Challenges of driving CD30-directed CAR-T cells to the clinic. [2020]

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

Dawn of Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. [2022]

7. Denmark pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. [2022]

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

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

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

CD19-directed CAR T-cell therapy in B-cell NHL. [2021]

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

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. [2022]