Immunotherapy for Lymphoma

Overseen By Clinical Trial Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Medical College of Wisconsin

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Uncontrolled infection, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment where a patient's immune cells are enhanced to better fight cancer. It targets adults whose CD30+ cancer has come back or resisted other treatments. The enhanced cells are designed to specifically attack cancer cells, making the immune system more effective against the disease.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any investigational agents within 14 days of enrollment, and you should not be on chronic systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial.

What data supports the effectiveness of the treatment CD30 biAb-AATC for lymphoma?

Research shows that treatments targeting CD30, like CD30-directed CAR-T cells and bispecific antibodies, have shown promise in treating Hodgkin lymphoma by effectively targeting cancer cells while sparing healthy cells. These treatments have demonstrated high response rates and low toxicity, suggesting that CD30 biAb-AATC could also be effective. ^{1 2 3 4 5}

Is the immunotherapy treatment CD30 biAb-AATC generally safe for humans?

The treatment involving CD30-targeted therapies, including CD30 biAb-AATC, has shown a favorable safety profile in clinical trials. Common side effects reported include chills, fever, and fatigue, but serious toxicities were not observed, and patients' physical function and symptom burden generally returned to baseline levels within a month after treatment. ^{2 4 6 7 8}

How is the treatment CD30 biAb-AATC different from other treatments for lymphoma?

CD30 biAb-AATC is unique because it uses bispecific antibodies to target both the CD30 antigen on lymphoma cells and the CD3 antigen on T cells, enhancing the body's immune response against the tumor. This approach aims to improve safety and effectiveness by using non-genetically modified T cells, unlike other treatments that may involve more complex genetic modifications. ^{1 2 5 9 10}

Research Team

Nathan Schloemer, MD

Principal Investigator

Medical College of Wisconsin / Children's Wisconsin

Eligibility Criteria

This trial is for people aged 12-39 with certain CD30+ cancers like lymphoma and leukemia, who have measurable disease and no effective standard treatments left. They must be in good health otherwise, not pregnant or breastfeeding, willing to use contraception, and haven't had some other cancer in the last 5 years.

Inclusion Criteria

My cancer cells test positive for CD30.

Life expectancy of >12 weeks

Patients must have specific bone marrow blast percentage for leukemias

Exclusion Criteria

I have not experienced severe side effects from previous treatments.

No known hypersensitivity to study components

Treatment with any investigational agent within 14 days of enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

T-cell Collection and Bridging Chemotherapy

T-cell collection followed by a recommended 21-day bridging chemotherapy while the CD30 biAb-AATC product is generated and quality control is assessed

3 weeks

Treatment

Weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF in 4-week cycles for a maximum of two total cycles

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• CD30 biAb-AATC

Trial Overview The trial tests a new immunotherapy using patients' own T-cells armed with a special CD30 antibody against their cancer. It's the first time this treatment is being tried on humans to see if it's safe and works.

Participant Groups

Group I: CD30biAb-AATC Experimental Treatment 1 Intervention

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF in 4-week cycles for a maximum of two total cycles.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Midwest Athletes Against Childhood Cancer

Collaborator

Trials

1

Recruited

40+

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]

CAR T cells targeting CD30 show promise in treating lymphoma without depleting healthy B cells, as they do not attack CD30(+) hematopoietic stem and progenitor cells (HSPCs).

The study demonstrated that anti-CD30 CAR T cells maintain normal blood cell levels in humanized mice, indicating a safer therapeutic profile compared to CD19-targeting CAR T cells, which can lead to lasting depletion of healthy B cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. Hombach, AA., Görgens, A., Chmielewski, M., et al.[2018]

In a phase I study involving 9 patients with relapsed/refractory Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL), CD30-targeted CAR T-cell therapy was found to be safe, with no observed toxicities related to the treatment.

The therapy resulted in significant clinical responses, including complete responses in 2 patients and stable disease in several others, suggesting that CD30.CAR-Ts could be an effective treatment option for these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. Ramos, CA., Ballard, B., Zhang, H., et al.[2022]

The bispecific antibody CD20-TCB is designed to enhance T-cell engagement, which could improve the effectiveness of immunotherapy in treating B-cell lymphoma, particularly in patients with relapsed or refractory non-Hodgkin lymphoma.

Preclinical models have shown promising activity for CD20-TCB, suggesting it may offer a new therapeutic option for patients who have not responded to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. Prakash, A., Diefenbach, CS.[2019]

The addition of the anti-CD20 monoclonal antibody rituximab to standard therapies has significantly improved overall survival rates in newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Innovative T-cell redirecting therapies, such as bispecific antibodies targeting both T-cell and B-cell antigens, have shown impressive efficacy in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma, leading to ongoing clinical trials exploring their combinations with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. Russler-Germain, DA., Ghobadi, A.[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. Switzerland pubmed.ncbi.nlm.nih.gov

Novel anti-CD30/CD3 bispecific antibodies activate human T cells and mediate potent anti-tumor activity. [2023]

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

Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. [2018]

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

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

5. Germany pubmed.ncbi.nlm.nih.gov

Immune recruitment by bispecific antibodies for the treatment of Hodgkin disease. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: a pilot study. [2021]

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

Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. [2022]

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

CD20-targeted T cells after stem cell transplantation for high risk and refractory non-Hodgkin's lymphoma. [2021]

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

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. [2023]