CAR T-cells for Hodgkin's Lymphoma

Overseen By Lauren Harrison, MSN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: New York Medical College

Disqualifiers: Age, Performance score, others

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

Compensation: Varies

Number of Visits: Unknown

21 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

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

Research shows that CD30 CAR T-cell treatment can be effective for Hodgkin's Lymphoma, with some patients experiencing partial remission or stable disease. The treatment is generally safe, with low toxicity, and patients often return to their baseline health within a month after treatment. ^{1 2 3 4 5}

Is CD30 CAR T-cell therapy safe for humans?

CD30 CAR T-cell therapy for Hodgkin's Lymphoma has shown to be generally safe with low rates of side effects, including mild cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and no observed neurotoxicity (nerve damage). Patient-reported outcomes indicate that physical function and symptom burden return to baseline levels within a month after treatment. ^{1 4 5 6 7}

How does the CD30 CAR T-cell treatment differ from other treatments for Hodgkin's Lymphoma?

The CD30 CAR T-cell treatment is unique because it uses genetically modified T-cells to specifically target the CD30 protein found on Hodgkin's Lymphoma cells, which is not present in most healthy tissues. This approach aims to improve the effectiveness of treatment by enhancing the T-cells' ability to locate and attack cancer cells, offering a novel option for patients with relapsed or refractory Hodgkin's Lymphoma. ^{1 2 3 4 8}

What is the purpose of this trial?

Patients with poor risk classical Hodgkin Lymphoma (cHL) will undergo myeloablative chemotherapy (MAC) with autologous stem cell transplantation (AutoHSCT) and subsequently receive autologous CD30+ CAR T-cells.

Eligibility Criteria

This trial is for individuals with a high-risk form of Hodgkin Lymphoma who have undergone intense chemotherapy and stem cell transplant. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments.

Inclusion Criteria

I am between 6 and 29 years old.

I can do most activities but may need help.

I meet at least two risk factors for my condition based on specific health scores and cancer characteristics.

Exclusion Criteria

Not meeting the inclusion criteria

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Collection of peripheral blood mononuclear cells (PBMC) for CD30+ CAR T-cell manufacturing and autologous stem cells (PBSC) for future AutoHSCT

2-4 weeks

Myeloablative Conditioning and AutoHSCT

Patients receive BEAM conditioning followed by autologous stem cell transplantation (AutoHSCT)

3-6 weeks

CAR T-cell Infusion

Patients receive autologous CD30+ CAR T-cell infusion between days 21-42 post AutoHSCT

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and toxicities

2 years

Treatment Details

Interventions

• CD30 CAR T-cell

Trial Overview The study tests the use of CD30 CAR T-cells in patients after they've received myeloablative chemotherapy followed by an autologous stem cell transplant to treat poor-risk classical Hodgkin Lymphoma.

Participant Groups

Group I: CD30 CAR T-cells Experimental Treatment 1 Intervention

Patients will receive autologous CD30 CAR T-cells post autologous stem cell transplant between days 21-42.

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

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]

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]

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]

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]

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]

References

1. 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]

2. United States 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. [2022]

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

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

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

The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

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

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

7. 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]

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

Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. [2023]