CAR-T Cell Therapy for Hodgkin Lymphoma

Not currently recruiting at 4 trial locations

Overseen By Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Tessa Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CD30.CAR-T, a type of CAR-T cell therapy, for individuals with classical Hodgkin Lymphoma that hasn't responded to at least three other treatments. The trial aims to determine the safety and effectiveness of this treatment. It targets patients whose lymphoma persists or recurs and who have CD30-positive tumors. This trial may suit those who have struggled with treatments like chemotherapy or stem cell transplants and still have a measurable tumor. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive drugs or chronic systemic corticosteroids, and you must not have received certain treatments like anti-CD30 antibody-based therapy or investigational agents within specific time frames before the trial.

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

Research has shown that anti-CD30 CAR-T cell therapy is generally safe for individuals with relapsed or hard-to-treat classical Hodgkin Lymphoma. Studies have found that this treatment is usually well-tolerated, with few side effects. For instance, in one study, all patients survived for at least two years, indicating good safety results. Another study reported that patients responded well to the treatment, which proved effective with minimal side effects. Overall, current evidence supports the safety of CD30.CAR-T therapy for these patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CD30.CAR-T is unique because it uses a patient's own immune cells, which are genetically engineered to specifically target and destroy cancer cells expressing the CD30 protein, commonly found in Hodgkin Lymphoma. Unlike the standard treatments such as chemotherapy, radiation, or stem cell transplants, which broadly attack cancer and healthy cells alike, CD30.CAR-T offers a more targeted approach, potentially reducing side effects. Researchers are excited because this precision targeting could offer new hope for patients who have not responded to multiple previous treatments.

What evidence suggests that CD30.CAR-T might be an effective treatment for Hodgkin Lymphoma?

Research shows that CD30.CAR-T cell therapy, which participants in this trial will receive, can effectively treat classical Hodgkin Lymphoma that has returned or resisted other treatments. Studies have found high success rates, with some patients experiencing long-lasting improvements. For example, one study found that one patient had a complete response, and four others had partial responses, with these improvements lasting an average of 7.8 months. Another source notes that even after previous treatments, many patients still respond well to this therapy. Overall, these findings suggest that CD30.CAR-T therapy could be a promising option for those who haven't had success with other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Helen Heslop, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals aged 12-75 with relapsed or refractory classical Hodgkin Lymphoma, who have tried at least three prior therapies. They must have CD30-positive tumors, measurable lesions, adequate organ function and no severe heart or lung issues. Excluded are those with CNS lymphoma involvement, recent other cancer treatments, active infections like HIV/HBV/HCV, ongoing immunosuppression therapy, certain cardiovascular diseases or pregnancy.

Inclusion Criteria

My kidney function is good.

Signed Informed Consent Form

Hgb ≥ 8.0 g/dL

Exclusion Criteria

I am currently taking drugs that suppress my immune system or long-term steroids.

I do not have active seizures, stroke, brain blood flow issues, severe memory loss, balance disorders, or autoimmune diseases affecting my brain.

I have a bleeding condition that is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Bridging Chemotherapy

Blood is drawn for CD30.CAR-T cell manufacturing; bridging chemotherapy may be administered

3-4 weeks

Lymphodepletion and CD30.CAR-T Infusion

Lymphodepletion with fludarabine and bendamustine followed by CD30.CAR-T infusion

1 week

3 visits (in-person) for lymphodepletion, 1 visit (in-person) for infusion

Treatment Monitoring

Participants are closely monitored for safety and efficacy until the end of study visit at Month 24

24 months

Long-term Follow-up

Participants enter long-term follow-up for survival, safety, efficacy, and biomarker assessments

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• CD30.CAR-T

Trial Overview The CHARIOT study tests the safety and effectiveness of a personalized immune cell therapy called autologous CD30.CAR-T cells in patients with specific types of Hodgkin Lymphoma that haven't responded to previous treatments. It's an open-label trial where all participants receive the same experimental treatment without a comparison group.

How Is the Trial Designed?

Group I: CD30 positive r/r classical Hodgkin Lymphoma Experimental Treatment 3 Interventions

Patients with relapsed or refractory classical Hodgkin Lymphoma who have failed 3 prior lines of treatment, which may include a prior autologous and/or allogeneic stem cell transplant. Patients will be treated with autologous CD30.CAR-T cells.

Who Is Running the Clinical Trial?

Tessa Therapeutics

Lead Sponsor

Trials

4

Recruited

460+

Published Research Related to This Trial

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]

Third-generation anti-CD30 CAR T-cells (CD28BBz) show long-term persistence and strong anti-tumor activity in models of Hodgkin lymphoma and anaplastic large cell lymphoma, outperforming second-generation CAR T-cells (CD28z).

These CAR T-cells are well tolerated with minimal side effects, indicating they are a safe and effective treatment option for patients with Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. Zhang, S., Gu, C., Huang, L., et al.[2022]

Chimeric antigen receptor (CAR)-transduced T cells targeting CD30 have shown to be safe and effective in treating Hodgkin lymphoma (HL).

The review also highlights the challenges and ongoing trials of using CAR-T cells targeting CD5 and CD7 in T-cell lymphomas (TCL), indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. Muhsen, IN., Hill, LC., Ramos, CA.[2023]

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]

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]

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]

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-targeting CAR T cell therapy was found to be safe and feasible for patients with relapsed or refractory Hodgkin lymphoma, with only two out of 18 patients experiencing severe toxicities.

Of the 18 patients treated, 7 achieved partial remission and 6 had stable disease, indicating that while the therapy shows promise, responses varied, particularly with lymph nodes responding better than lung lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial. Wang, CM., Wu, ZQ., Wang, Y., et al.[2022]

Citations

1. 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.

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10656097/

CAR-T Cell Therapy for Classical Hodgkin Lymphoma One patient achieved a complete response and 4 patients achieved partial responses with a median duration of response of 7.8 months.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04268706

Phase 2 Study Evaluating Autologous CD30.CAR-T Cells ... This is a two-part, Phase 2, multicenter, open-label, single arm study to evaluate the safety and efficacy of autologous CD30.CAR-T in adult and pediatric ...

5. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/12723/493011/Clinical-Activity-of-Anti-PD-1-Therapy-Following

Clinical Activity of Anti-PD-1 Therapy Following CD30 CAR-T ... Clinical efficacy appears strong, with high response rates and durable remissions observed even if most patients had prior exposure to anti-PD-1 ...

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

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... Conclusion: 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 ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3465/529134/Safety-and-Efficacy-of-CD30-Directed-Chimeric

Safety and Efficacy of CD30-Directed Chimeric Antigen ... The estimated 2-year overall survival (OS) was 100% and the median OS for all cHL patients has not been reached. Expansion and/or persistence of ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302624000644

Anti-CD30 CAR T cells as consolidation after autologous ... Anti-CD30 CAR T-cell infusion as consolidation after BEAM and autologous HSCT is safe, with low rates of toxicity and encouraging preliminary activity.