CD30 CAR T-Cell Therapy for Lymphoma

Overseen By Caroline Babinec

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Corticosteroids, CYP1A2 inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration. In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. The purpose of this research study is to establish a safe dose of ATLCAR.CD30 cells to infuse after lymphodepleting chemotherapy and to estimate the number patients whose cancer does not progress for two years after ATLCAR.CD30 administration. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on the patient's cancer.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. You must not have received any investigational agents, tumor vaccines, or anti-CD30 antibody-based therapy within specific time frames before cell infusion. Additionally, you cannot use systemic corticosteroids at doses of 10 mg prednisone daily or more, and you must avoid strong inhibitors of CYP1A2 if you receive bendamustine for lymphodepletion.

Is CD30 CAR T-cell therapy safe for humans?

CD30 CAR T-cell therapy has shown some safety concerns, such as cytokine release syndrome (CRS), which can be serious but was mostly mild in studies. No severe brain-related side effects were observed, and the therapy is generally considered to have minimal toxicities in patients with CD30+ lymphoma. ^{1 2 3 4 5}

How is CD30 CAR T-Cell Therapy different from other treatments for lymphoma?

CD30 CAR T-Cell Therapy is unique because it uses genetically modified T-cells to specifically target and attack lymphoma cells that express the CD30 protein, which is common in certain types of lymphoma like Hodgkin lymphoma. This approach is different from traditional treatments as it involves reprogramming the patient's own immune cells to fight the cancer, offering a personalized and potentially more effective treatment option for those with relapsed or refractory lymphoma. ^{6 7 8 9 10}

What data supports the effectiveness of the CD30 CAR T-Cell treatment for lymphoma?

Research shows that CD30 CAR T-Cell treatment has been effective in some patients with relapsed or refractory CD30+ lymphomas, with a high overall response rate and some achieving complete remission. The treatment has shown promise, especially when combined with other therapies like PD-1 inhibitors, enhancing its effectiveness with minimal side effects. ^{2 6 9 11 12}

Who Is on the Research Team?

Anne Beaven, MD

Principal Investigator

Director, UNC Lineberger Lymphoma Program

Are You a Good Fit for This Trial?

This trial is for adults and children with certain types of lymphoma (HL and NHL) that have returned or resisted treatment. Participants must not be pregnant, should use birth control if applicable, cannot have severe infections like HIV/HCV/HTLV, no recent cancer vaccines or CD30 antibody therapy, and must have good organ function. They also shouldn't be on high-dose steroids or medications that interfere with the chemotherapy drug bendamustine.

Inclusion Criteria

My doctor thinks I am a good candidate for ATLCAR.CD30 treatment.

Informed consent explained to, understood by and signed by the subject or legal guardian for pediatric subjects; subject and/or legal guardian given a copy of informed consent form for procurement

My Hodgkin's or non-Hodgkin's lymphoma has returned after 2+ treatments.

Exclusion Criteria

My tumor is located where it could block my airway if it grows.

My tumor is located where it could block my airway if it grows.

I do not have active Hepatitis B infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Lymphodepletion with bendamustine and fludarabine for 3 consecutive days prior to ATLCAR.CD30 cell infusion

1 week

3 visits (in-person)

Treatment

Administration of ATLCAR.CD30 cells via intravenous injection, with potential for a second infusion at 6 weeks if partial response or stable disease is observed

6 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and adverse events, with follow-up for up to 15 years for RCR evaluation or until death

15 years

What Are the Treatments Tested in This Trial?

Interventions

• ATLCAR.CD30 cells

Trial Overview The study tests ATLCAR.CD30 cells in patients after chemotherapy to find a safe dose and see how well it prevents cancer progression over two years. These are T cells modified with a new gene to target CD30+ lymphoma cells more effectively by using a combination of antibodies and T cell mechanisms.

How Is the Trial Designed?

Group I: ATLCAR.CD30 cells Experimental Treatment 1 Intervention

Phase Ib: In adults, and separately, in children, two doses will be investigated 1x10\^8 cells/m2 and 2x10\^8 cells/m\^2. The study team will run two independent dose-escalation sequences, one for adults and another one for children. The study team plans to use the 3+3 design and start with a low dose of 1x10\^8 cells/m2. If there are no DLT in first 3 patients, the study team will go up to the dose of 2 x 10\^8 cells/m2. If there is toxicity in 1/3 patients in the initial cohort, the study team would expand to enroll up to 6 patients. If there are dose limiting toxicities (DLT) at the dose of 2 x 10\^8 cells/m\^2, the study team will initially decrease the dose to an intermediate dose of 1.5 x 10\^8 cells/m\^. Phase II: The study team planning to enroll 31 patients to contribute data. Sequential boundary will be used to monitor DLT rate.

ATLCAR.CD30 cells is already approved in United States, European Union for the following indications:

Approved in United States as CD30 CAR-T cells for:

• Relapsed or refractory classical Hodgkin lymphoma

Approved in European Union as CD30 CAR-T cells for:

• Relapsed or refractory classical Hodgkin lymphoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

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 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-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 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]

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]

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]

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 can effectively treat B cell malignancies but poses safety risks by also destroying healthy B cells that express the same antigen, leading to potential long-term tissue damage.

Research suggests that targeting activation-associated antigens, which are only temporarily present on stem cells, is safer than targeting lineage-associated antigens, which can harm tissue stem cells during their maturation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? Hombach, AA., Abken, H.[2017]

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 cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

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]

Citations

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

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

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. 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]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? [2017]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]

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

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