MUC1-Activated T-Cells for Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment using MUC1-activated T-cells to help the immune system combat multiple myeloma, a type of blood cancer, especially when it has returned or isn't responding to existing treatments. The study examines the safety and optimal dosage of these T-cells, which are specially modified to target a specific protein (MUC1) found in cancer cells. Participants will also receive a chemotherapy drug called cyclophosphamide. Individuals with multiple myeloma who have a confirmed presence of the MUC1 protein and have tried at least three other treatments without success might be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative 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, patients on chronic high-dose steroids or other investigational cancer treatments are excluded, so you may need to adjust those if applicable.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MUC1-based treatments are usually safe. Some studies reported that patients experienced only mild to moderate side effects, such as fatigue or flu-like symptoms. MUC1-activated T-cells remain in early testing stages, where researchers focus on identifying possible side effects and determining the optimal dose. As this is phase 1 research, the safety information may not yet be comprehensive. However, earlier trials have generally found these treatments to be safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which typically include chemotherapy, targeted therapy, and stem cell transplants, the MUC1-activated T-cells offer a novel approach by harnessing the body's immune system directly. These T-cells are engineered to recognize and attack cancer cells expressing the MUC1 protein, which is often overexpressed in multiple myeloma. This targeted immune response could potentially improve effectiveness and reduce side effects compared to traditional therapies. Researchers are excited because this method represents a shift towards personalized medicine, offering a new hope for patients with multiple myeloma.

What evidence suggests that MUC1-activated T-cells could be an effective treatment for multiple myeloma?

Research has shown that specially designed T-cells can recognize and attack myeloma cells, potentially aiding in the treatment of multiple myeloma. These T-cells target a protein called MUC1 found on myeloma cells. In lab studies, these T-cells slowed tumor growth. This trial will evaluate the effectiveness of MUC1-activated T-cells, administered with cyclophosphamide, in enhancing the immune system's ability to find and destroy cancer cells. Although researchers are still studying this treatment, early results are promising for individuals with multiple myeloma that has returned or is not responding to other treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

Leif Bergsagel, M.D.

Principal Investigator

Mayo Clinic Hospital in Arizona

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05411497

Genetically Engineered Cells (MUC1-Activated T-Cells) for ... This phase I trial tests the safety, side effects and best dose of MUC1-activated T cells in treating patients with multiple myeloma that has come back ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20533789

Genetically Engineered Cells (MUC1-Activated T-Cells) for ... Primary Goal: To determine the toxicity of in-house, manufactured MUC1-activated T cells in patients with relapsed/refractory MUC1-expressing multiple myeloma.

3. withpower.com withpower.com/trial/phase-1-recurrent-plasma-cell-myeloma-6-2022-1d323

MUC1-Activated T-Cells for Multiple Myeloma Studies have demonstrated that T-cells activated against MUC1 can recognize and attack myeloma cells, suggesting potential effectiveness in treating multiple ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5358667/

Engineered CAR T Cells Targeting the Cancer-Associated ... Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and ...

5. nature.com nature.com/articles/s41417-024-00750-2

CAR T therapies in multiple myeloma: unleashing the future In terms of efficacy, CAR + T cells remained detectable in 81% of patients at 6 months and 60% at 12 months post-infusion. Among patients ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-03111

Genetically Engineered Cells (MUC1-Activated T-Cells) for ... This phase I trial tests the safety, side effects and best dose of MUC1-activated T cells in treating patients with multiple myeloma that has come back ...