Immunotherapy for Lymphoma

Not yet recruiting at 1 trial location

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment for certain blood cancers, such as Hodgkin's and Non-Hodgkin's Lymphoma, that have not responded to previous treatments. The treatment, CD30 biAb-AATC, uses a patient's own T-cells, specially prepared to target cancer cells. Individuals who have experienced multiple relapses or whose cancer did not respond to other treatments might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that treatments like CD30 biAb-AATC, which use a special type of antibody to target cancer cells, show promise in terms of safety. For instance, other treatments using anti-CD30 antibodies have proven effective and generally safe for certain cancers. However, since researchers are testing CD30 biAb-AATC in humans for the first time, the research is still in its early stages.

The trial is in its first phase, focusing mainly on assessing the treatment's safety. This phase begins with low doses to observe the body's response, gradually increasing the dose while monitoring for side effects. This process helps researchers determine a safe dose range and identify any potential side effects.

In summary, while similar treatments have previously been safe, this specific therapy is new and is being carefully studied to ensure its safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for lymphoma, which often involves chemotherapy or radiation, CD30 biAb-AATC is a cutting-edge immunotherapy leveraging bi-specific antibodies. This treatment is designed to target CD30, a specific protein found on the surface of some lymphoma cells, offering a more precise attack on the cancer while sparing healthy cells. Additionally, the use of GM-CSF in conjunction with the antibody therapy potentially enhances the body's immune response, making it a promising option for patients. Researchers are particularly excited about its potential to improve outcomes with fewer side effects compared to traditional therapies.

What evidence suggests that CD30 biAb-AATC might be an effective treatment for lymphoma?

Research has shown that CD30 biAb-AATC is a promising new treatment for lymphoma, particularly for patients with CD30-positive cancers. This trial will explore different dose levels of CD30 biAb-AATC, which uses a special antibody to target CD30, a protein often found on cancer cells, and CD3, which helps activate T-cells to fight the cancer. Early studies on similar treatments, such as anti-CD30 CAR-T cells, showed encouraging results: 39% of patients experienced no cancer growth after one year, and 89% remained alive. These findings suggest that targeting CD30 can help control cancer and improve survival. While more research is needed to confirm these results, the CD30 biAb-AATC approach builds on these promising findings. ^{1 2 4 6 7}

Who Is on the Research Team?

Guru Subramanian Guru Murthy, MD, MS

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: CD30biAb-AATC Recommended Phase 2 Dose (RP2D) Experimental Treatment 2 Interventions

The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed.

Group II: CD30biAb-AATC (Dose Level 3 -- 160 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2) Experimental Treatment 2 Interventions

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Group III: CD30biAb-AATC (Dose Level 2 -- 120 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2) Experimental Treatment 2 Interventions

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Group IV: CD30biAb-AATC (Dose Level 1 -- 80 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2) Experimental Treatment 2 Interventions

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Group V: CD30biAb-AATC (Dose Level -1 -- 40 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2) Experimental Treatment 2 Interventions

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

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+

Published Research Related to This Trial

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10461807/

Novel anti-CD30/CD3 bispecific antibodies activate human ... Further, for patients with primary refractory or relapsed disease, outcomes are poor, with 5-year overall survival rates between 20%-31% (10, 11) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05544968

NCT05544968 | CD30biAb-AATC for CD30+ Malignancies This first-in-human trial will assess the safety, feasibility, and efficacy of an immunotherapy with a novel CD30 antibody conjugated to a CD3 antibody that ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11731380/

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... With the median follow-up range from 9.5 to 71.5 months, the 1-year PFS was 39% (95% CI 0.30–0.49, P = 0.04), and the 1-year OS was 89% (95% CI ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05544968?keyword=%22Lymphoma%3A%20Hodgkin%22

CD30biAb-AATC for CD30+ Malignancies Non-randomized, single arm, dose escalating, Phase I study evaluating the feasibility and safety of a novel anti-CD30 biAb-AATC product for adult patients ...

5. synapse.patsnap.com synapse.patsnap.com/drug/5ad447500e1e4b5698a605c6f2d8dd53

anti-CD30 Bispecific Antibody-armed anti-CD3-Activated ... Study to investigate the safety, tolerability, and preliminary efficacy of anti-CD30 bispecific antibody-armed anti-CD3-activated autologous T-cells.

6. trials.braintumor.org trials.braintumor.org/trials/NCT05544968

CD30biAb-AATC for CD30+ Malignancies - Clinical Trial Finder This first-in-human trial will assess the safety, feasibility, and efficacy of an immunotherapy with a novel CD30 antibody conjugated to a CD3 antibody that is ...

7. 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 ...