MUC1-Activated T-Cells for Multiple Myeloma

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Steroids, Investigational agents

Disqualifiers: CNS metastases, Plasma cell leukemia, others

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

Compensation: Varies

Number of Visits: 5

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment using modified T cells to target a specific protein on cancer cells in patients with difficult-to-treat multiple myeloma. The goal is to see if these specially trained cells can help the immune system kill cancer cells more effectively. This new method for cancer treatment shows promise in treating multiple myeloma.

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, patients on chronic high-dose steroids or other investigational cancer treatments are excluded, so you may need to adjust those if applicable.

What data supports the effectiveness of the treatment MUC1-Activated T-Cells for Multiple Myeloma?

Research shows that MUC1, a protein found on myeloma cells, can be targeted by the immune system. Studies have demonstrated that T-cells activated against MUC1 can recognize and attack myeloma cells, suggesting potential effectiveness in treating multiple myeloma. ^{1 2 3 4 5}

Is MUC1-activated T-cell therapy safe for humans?

Clinical trials using MUC1-based vaccines have shown that they are generally safe, with some patients experiencing mild to moderate side effects. In a study of a similar T-cell therapy for multiple myeloma, the treatment was well tolerated with only two patients experiencing temporary, moderate infusion-related reactions. ^{1 4 6 7 8}

What makes the MUC1-activated T-cells treatment unique for multiple myeloma?

This treatment is unique because it uses the patient's own T-cells, which are activated to specifically target the MUC1 protein found on multiple myeloma cells, potentially enhancing the immune system's ability to fight the cancer. ^{1 2 4 9 10}

Research Team

Leif Bergsagel, M.D.

Principal Investigator

Mayo Clinic Hospital in Arizona

Eligibility Criteria

This trial is for adults over 18 with recurrent or treatment-resistant multiple myeloma that expresses MUC1. Participants must have tried at least three prior therapies, including a proteasome inhibitor, an IMiD, and a CD38 antibody. They should be in good general health with stable vital signs and able to provide consent. Pregnant or nursing individuals and those unwilling to use birth control are excluded.

Inclusion Criteria

I am willing to have a procedure to collect blood components.

Your oxygen level is 90% or higher when you breathe normally.

My cancer outside the bone marrow meets the required size criteria.

Exclusion Criteria

I need high doses of steroids every day for my condition.

I had a heart attack more than 6 months ago or I am being treated for heart failure.

I do not have any uncontrolled illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Chemotherapy

Patients receive cyclophosphamide intravenously over 60 minutes on days -5, -4, -3

1 week

3 visits (in-person)

Autologous Stem Cell Transplantation

Patients receive MUC1-activated T-cells intravenously over 10 minutes to 1 hour on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits on days 1, 2, 3, 7, 28 and every 90 days

Treatment Details

Interventions

• Autologous MUC1-activated T-cells
• Cyclophosphamide

Trial Overview The trial tests genetically engineered T-cells designed to target the MUC1 marker on cancer cells in patients with multiple myeloma. It aims to find the safest dose of these modified T-cells when combined with Cyclophosphamide, assessing how well they help the immune system fight cancer.

Participant Groups

Group I: Treatment (cyclophosphamide, MUC1-activated T-cells) Experimental Treatment 2 Interventions

LD CHEMOTHERAPY: Patients receive cyclophosphamide IV over 60 minutes on days -5, -4, -3. ASCT: Patients receive MUC1-activated T-cells IV over 10 minutes to 1 hour on day 0.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving six multiple myeloma patients, cytotoxic T lymphocyte (CTL) lines were successfully induced from two patients, demonstrating the potential to target MUC1, a tumor-associated antigen, in myeloma and breast carcinoma cells.

The CTL lines showed effective cytotoxicity against MUC1+ cancer cells, and their activity was specifically inhibited by antibodies targeting MUC1, indicating that these CTLs can recognize and attack cancer cells expressing this antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic T lymphocytes derived from bone marrow mononuclear cells of multiple myeloma patients recognize an underglycosylated form of MUC1 mucin. Noto, H., Takahashi, T., Makiguchi, Y., et al.[2019]

An autologous T cell therapy targeting multiple tumor-associated antigens (mTAAs) was tested in 21 patients with high-risk, relapsed or refractory multiple myeloma, showing good tolerance with only two cases of transient grade III adverse events.

Patients receiving this therapy experienced longer than expected progression-free survival, with some achieving objective responses, indicating that this approach may provide a promising long-term benefit for difficult-to-treat multiple myeloma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma. Lulla, PD., Tzannou, I., Vasileiou, S., et al.[2021]

Monoclonal antibodies like elotuzumab and daratumumab have advanced the treatment of multiple myeloma, while CAR T cell therapy is emerging as a promising option for patients with relapsed/refractory multiple myeloma, offering hope for those with limited treatment options.

Despite its potential efficacy, CAR T cell therapy can lead to severe adverse events and toxic deaths, highlighting the need for better understanding and management strategies for these toxicities in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies. Zhou, X., Rasche, L., Kortüm, KM., et al.[2021]

References

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

Cytotoxic T lymphocytes derived from bone marrow mononuclear cells of multiple myeloma patients recognize an underglycosylated form of MUC1 mucin. [2019]

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

Mucin 1-specific active cancer immunotherapy with tecemotide (L-BLP25) in patients with multiple myeloma: an exploratory study. [2021]

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

Lentiviral transduction of primary myeloma cells with CD80 and CD154 generates antimyeloma effector T cells. [2017]

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

Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Cellular Immunotherapies for Multiple Myeloma: Current Status, Challenges, and Future Directions. [2022]

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

The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies. [2021]

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

A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1. [2019]

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

The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. [2022]

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

MUC1/KL-6 expression confers an aggressive phenotype upon myeloma cells. [2019]