CAR-T Cell Therapy for Lymphoma

Overseen By Caroline Babinec

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Brentuximab vedotin

Must not be taking: Systemic corticosteroids, CYP1A2 inhibitors

Disqualifiers: Pregnancy, HIV, HBV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using lab-modified immune cells to target and kill cancer cells in patients with certain types of lymphoma that haven't responded to other treatments. The modified cells are designed to better locate and destroy cancer cells. This new approach extends the capacity of the patient's own immune cells to detect and eliminate cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use strong inhibitors of CYP1A2 (like fluvoxamine or ciprofloxacin) during certain parts of the study. Also, you cannot be on systemic corticosteroids at doses of 10mg or more of prednisone daily.

What data supports the effectiveness of this treatment for lymphoma?

Research shows that CD30-directed CAR-T cells, which are part of this treatment, have shown promising results in targeting lymphoma cells, particularly in Hodgkin lymphoma and other CD30+ lymphomas. These studies indicate that the treatment can effectively target and destroy cancer cells, although improvements in persistence and expansion of the CAR-T cells are needed to enhance long-term effectiveness. ^{1 2 3 4 5}

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

CAR-T cell therapy targeting CD30 has been shown to be generally safe in humans, with studies indicating it is well tolerated and has minor side effects. However, long-term follow-up is important to monitor any late toxicity. ^{4 6 7 8 9}

What makes the CAR-T cell therapy treatment for lymphoma unique?

This treatment uses specially engineered T-cells to target the CD30 protein found on certain lymphoma cells, offering a new option for patients whose cancer does not respond to traditional therapies. It is unique because it combines the CD30 target with CCR4, potentially enhancing the T-cells' ability to find and attack cancer cells. ^{3 6 10 11 12}

Research Team

Natalie S. Grover

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with certain types of lymphoma, like Mycosis fungoides or Sezary syndrome, that have not improved after at least two treatments. Participants must have CD30+ disease and adequate organ function. They cannot be on strong CYP1A2 inhibitors, have uncontrolled infections, or be pregnant. Those with HIV, HTLV, HCV or active hepatitis B are excluded.

Inclusion Criteria

Subjects must have one of the following diagnoses by WHO criteria: Classic Hodgkin Lymphoma, Mycosis fungoides, Sezary syndrome, Primary cutaneous CD30 positive T cell lymphoproliferative disorder including lymphomatoid papulosis or primary cutaneous anaplastic large cell lymphoma, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin Lymphoma (Grey Zone Lymphoma), Diagnosis of recurrent lymphoma in subjects who have failed ≥2 prior treatment regimens (including brentuximab vedotin), Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study, CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells)

I am willing to have a biopsy after receiving cell infusion.

I have signed the consent form for the CAR T-cell therapy trial before starting lymphodepletion.

Exclusion Criteria

I have another cancer that is growing and needs treatment.

I do not have an active HIV, HTLV, or HCV infection.

I do not have any ongoing serious infections.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Up to 300 mL total of peripheral blood will be obtained for cell procurement, with leukapheresis performed if necessary.

1-2 weeks

Up to 3 visits (in-person)

Lymphodepletion

Subjects will receive lymphodepletion with bendamustine and fludarabine for 3 days prior to CAR-T cell infusion.

1 week

3 visits (in-person)

Treatment

Administration of ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells, with potential for a second infusion.

1-2 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including long-term follow-up for replication competent retrovirus (RCR) evaluation.

15 years

Treatment Details

Interventions

• ATLCAR.CD30 (CAR T-cell Therapy)
• ATLCAR.CD30.CCR4 (CAR T-cell Therapy)
• Bendamustine (Alkylating agents)
• Fludarabine (Anti-metabolites)

Trial Overview The study tests new cancer treatments using T cells genetically modified to target CD30+ lymphoma cells. One group receives ATLCAR.CD30.CCR4 cells designed to navigate towards tumors; another gets these plus additional ATLCAR.CD30 cells. The goal is to find the safest dose for these therapies.

Participant Groups

Group I: ATLCAR.CD30.CCR4 & ATLCAR.CD30 Experimental Treatment 4 Interventions

A 3+3 design in adult subjects. Subjects in the first dose level will receive ATLCAR.CD30.CCR4 cells alone, once safety has been established, the initial dose of ATLCAR.CD30.CCR4 will be combined with a fixed dose of ATLCAR.CD30 cells in the next dose level. Every time the dose of ATLCAR.CD30.CCR4 is escalated, subjects in that dose level will receive ATLCAR.CD30.CCR4 alone prior to subsequent dose level enrolling subjects to receive a combination of fixed dose ATLCAR.CD30 and the selected dose level of ATLCAR.CD30.CCR4. The six dose levels will consist of: dose level 1 = 2 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 2 = 1 × 10\^8 ATLCAR.CD30 cells/m2 and 2 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 3 = 5 × 10\^7/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 4 = 1 × 10\^8 ATLCAR.CD30 cells/m2 and 5 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 5 = 1 × 10\^8/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 6 = 1 × 108 ATLCAR.CD30 cells/m2 and 1 × 108 ATLCAR.CD30.CCR4 cells/m2.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University Cancer Research Fund at Lineberger Comprehensive Cancer Center

Collaborator

Trials

5

Recruited

150+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

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]

The combination of autologous stem-cell transplantation (ASCT) and CAR30 T-cell therapy was found to be safe and effective in treating relapsed/refractory CD30+ lymphoma, with 83.3% of patients achieving a complete response after treatment.

In a pilot study involving 6 patients, all of whom had previously poor prognoses, the treatment resulted in successful engraftment and maintained responses over a median follow-up of 20.4 months, indicating promising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. Zhang, P., Yang, X., Cao, Y., 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]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

CAR T cell therapy has become an important treatment for certain blood cancers, with three types of anti-CD19 CAR-T cells already approved for use in the Czech Republic, and more trials underway for targeting other cancer-specific antigens.

While the management of CAR-T cell therapy has improved, including updated guidelines for early toxicity, long-term follow-up is essential due to potential late toxicities, highlighting the need for ongoing research to enhance efficacy and reduce side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. Jana, M., Tomáš, J., Michal, K., et al.[2022]

The study demonstrates that CD30-targeted CAR-T cell therapy is effective in treating recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL), showing significant tumor suppression in both laboratory and mouse model experiments.

The engineered 9C11-2 CAR T cells exhibited strong cytotoxic effects against CD30-positive cancer cells, indicating their potential as a promising therapeutic option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. Wu, Y., Chen, D., Lu, Y., 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]

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30(+) cutaneous lymphoma cells. [2020]

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

CD30 as a therapeutic target in adult haematological malignancies: Where are we now? [2023]

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

CARs and cancers: questions and answers. [2021]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. [2022]

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

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. [2022]

9. 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]

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

Chimeric Antigen Receptor-Engineered T Cell Therapy in Lymphoma. [2020]

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

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

12. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]