CS1-CAR T Therapy for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: Active infection, CNS pathology, others

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

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CS1-CAR T therapy for individuals with multiple myeloma, a type of blood cancer that has returned or resists other treatments. The trial aims to determine the optimal dose and assess side effects of this therapy, which uses modified immune cells to target and destroy cancer cells. Participants will first undergo chemotherapy followed by CS1-CAR T therapy. This trial may suit those with multiple myeloma that has relapsed or remains refractory despite several standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Do I need to stop taking 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 participate if you are receiving other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. Also, dependence on corticosteroids greater than or equal to 10 mg/day of prednisone or equivalent is not allowed, except for topical and inhaled corticosteroids or physiologic replacement for adrenal insufficiency.

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 participate if you are receiving other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. It's best to discuss your specific medications with the trial team.

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

Research has shown that CS1-CAR T therapy can target and kill multiple myeloma cells in lab tests and early human studies. In these studies, patients generally tolerated the treatment well, although, like many cancer treatments, it can cause side effects. Common side effects include fever, low blood cell counts, and tiredness. More serious side effects can occur but are less common.

Researchers closely monitor patients in these trials to manage any side effects. As this is an early-stage trial, the main focus is on determining the best dose and checking for safety issues. This means there may still be risks, as the treatment has not yet been fully tested in large groups. However, reaching this stage suggests that earlier findings support its potential safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which often include chemotherapy and targeted therapies, CS1-CAR T therapy is a type of immunotherapy that reprograms a patient’s own T cells to target and attack cancer cells. Researchers are excited about this treatment because it offers a personalized approach, potentially leading to more effective and longer-lasting responses. Additionally, CAR T therapy has shown promise in rapidly reducing cancer burden, which could be a game-changer for patients who have not responded well to traditional therapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that CS1-CAR T therapy, which participants in this trial will receive, could be a promising treatment for multiple myeloma. Studies have found that CS1-CAR T cells can effectively find and destroy multiple myeloma cells. These cells are specially designed to recognize a protein called CS1 on the surface of myeloma cells, enabling them to attack the cancer directly. Importantly, CS1 is mostly found on myeloma cells and not on healthy ones, making this treatment potentially safer. Early results suggest that CS1-CAR T cells might outperform some current treatments, demonstrating strong effectiveness in initial tests. This makes CS1-CAR T therapy a hopeful option for patients whose myeloma has returned or isn't responding to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Myo Htut

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with CS1 positive multiple myeloma that has relapsed or is refractory. Participants must have a good performance status, life expectancy of at least 16 weeks, and meet specific blood count and organ function criteria. They should not be on other treatments or have certain infections, autoimmune diseases, severe heart conditions, or CNS involvement by malignancy.

Inclusion Criteria

I am able to care for myself but may not be able to do active work.

You have been diagnosed with CS1+ MM by City of Hope (COH) Pathology Core.

Your AST levels are not more than 2.5 times the upper limit of normal.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I had a stem cell transplant using my own cells less than 3 months ago.

Prospective subjects who may not be able to comply with all study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Patients undergo leukapheresis over 2-4 hours to collect immune cells

1 day

1 visit (in-person)

Chemotherapy

Patients receive cyclophosphamide IV on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3

3-5 days

Daily visits (in-person) for chemotherapy administration

CS1-CAR T Therapy

Patients undergo CS1-CAR T therapy over 10-15 minutes on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

1 day, at least every 2 days for up to 14 days, weekly for 1 month, monthly for 1 year, then periodically

What Are the Treatments Tested in This Trial?

Interventions

• CS1-CAR T Therapy
• Cyclophosphamide
• Fludarabine
• Leukapheresis

Trial Overview The trial tests the safety and optimal dose of CS1-CAR T therapy after chemotherapy in treating relapsed/refractory multiple myeloma. It involves modifying immune cells to recognize and kill cancer cells using a lentiviral vector called CS1.

How Is the Trial Designed?

Group I: Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy) Experimental Treatment 4 Interventions

Patients undergo leukapheresis over 2-4 hours. Beginning 3-4 weeks, patients receive cyclophosphamide IV on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients then undergo CS1-CAR T therapy over 10-15 minutes on day 0.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study developed novel chimeric antigen receptors (CAR) targeting CS1 for treating multiple myeloma, showing that these CAR T cells effectively attack tumor cells in mice.

Combining lenalidomide with CS1 CAR T cells significantly enhanced their immune functions and antitumor activity, suggesting a promising approach for future clinical trials in treating relapsed multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma. Wang, X., Walter, M., Urak, R., et al.[2023]

Chimeric antigen receptor (CAR) T cell therapies targeting specific antigens like BCMA and CD19 are showing promise in treating relapsed/refractory multiple myeloma, indicating a potential shift in treatment strategies for this challenging disease.

Ongoing clinical trials are exploring dual-target CAR T cells, which may enhance treatment efficacy by targeting multiple antigens simultaneously, offering hope for improved outcomes in patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent updates on CAR T clinical trials for multiple myeloma. Lin, Q., Zhao, J., Song, Y., et al.[2023]

The study developed novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells that specifically target multiple myeloma cells, showing effective tumor cell killing in laboratory tests and in live models.

These CAR-T cells not only killed multiple myeloma cells but also secreted IFN-gamma, indicating a strong immune response, and they successfully inhibited tumor growth in vivo, paving the way for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma. Golubovskaya, V., Zhou, H., Li, F., et al.[2021]

CS1 CAR-T cell immunotherapy shows promise for treating relapsed refractory multiple myeloma, leveraging the specific biomarker CS1 found on myeloma cells.

The development of a CS1-Fc fusion protein allows for effective detection of CS1 CAR expression and enhances the activation and proliferation of CS1 CAR-T cells, potentially improving the efficacy of this immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eukaryotic expression, protein purification and biological effects research of human CS1-Fc fusion protein]. Chen, R., Wang, X., Li, Y., et al.[2020]

The study introduces a novel CAR T-cell design that targets two different antigens, BCMA and CS1, on multiple myeloma cells, showing consistent and potent anti-tumor activity in mouse models.

This dual-targeting approach resulted in superior survival rates in treated mice compared to traditional CAR T-cells that only target a single antigen, suggesting it could help overcome the issue of relapse due to antigen loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A compound chimeric antigen receptor strategy for targeting multiple myeloma. Chen, KH., Wada, M., Pinz, KG., et al.[2019]

CS1-targeted CAR T cells demonstrated enhanced activation and cytotoxicity against multiple myeloma (MM) cells in vitro and ex vivo, indicating their potential effectiveness in treating this cancer.

In mouse models, the use of CS1-CAR T cells significantly suppressed the growth of human MM cells and improved survival, suggesting that targeting CS1 could be a promising therapeutic strategy for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells. Chu, J., He, S., Deng, Y., et al.[2021]

In a study involving 16 patients with relapsed or refractory multiple myeloma, the bispecific CS1-BCMA CAR-T cells showed a high overall response rate of 81%, with 38% achieving a stringent complete response, indicating strong efficacy in targeting this challenging cancer.

The treatment had a manageable safety profile, with 38% of patients experiencing mild cytokine release syndrome and significant hematological adverse events, but no neurological toxicities were reported, suggesting a favorable safety outcome for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Li, C., Xu, J., Luo, W., et al.[2023]

T-cell redirecting bispecific antibodies and CAR T cells are effective treatments for multiple myeloma but are associated with significant adverse events, including cytokine release syndrome and neurotoxicity.

The European Myeloma Network recommends specific management strategies for these adverse events, such as premedication, corticosteroids, and monitoring for symptoms, to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Ludwig, H., Terpos, E., van de Donk, N., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03710421

Study Details | NCT03710421 | CS1-CAR T Therapy ... This phase I trial studies the side effects and best dose of CS1-chimeric antigen receptor (CAR) T therapy after chemotherapy in treating patients who have ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8533376/

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T ... These data for the first time demonstrate that novel CS1 and bispecific CS1-BCMA-CAR-T cells are effective in targeting MM cells and provide a basis for future ...

3. cancer.gov cancer.gov/clinicaltrials/NCI-2024-04623

WS-CART-CS1 for the Treatment of Patients with Recurrent ... WS-CART-CS1 is a CAR-T, a type of cancer immunotherapy. It involves altering the genes inside immune cells to help them attack the cancer.

4. nature.com nature.com/articles/s41375-022-01559-4

CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) ... High CS1 (SLAMF7) expression on myeloma cells and limited expression on normal cells makes it a promising target for CAR-T therapy. The CS1 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11897482/

CAR‐T cells in the treatment of multiple myeloma Preclinical data on CS1-CAR T cell therapy have shown superior efficacy compared to elotuzumab (49), and it is currently being investigated in ...

6. withpower.com withpower.com/trial/phase-1-multiple-myeloma-1-2019-7e892

CS1-CAR T Therapy for Multiple Myeloma The available research shows that CS1-CAR T Therapy is effective in treating multiple myeloma. Studies have demonstrated that CS1-CAR T cells can specifically ...