CAR-T Therapy for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Armin Ghobadi, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Other malignancy, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new CAR-T cell therapy (WS-CART-CS1) targeting CS1, a protein present in most patients with multiple myeloma, a cancer affecting plasma cells in the bone marrow. The trial aims to test the safety and effectiveness of this treatment for those who have tried at least three other therapies without success. It involves two parts: one to determine the right dose and another to expand that dose for more patients. Patients with multiple myeloma who have relapsed after several treatments might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic therapy for multiple myeloma at least 14 days before a specific procedure called leukapheresis. If you are on other investigational agents or have received cellular therapy recently, you may also need to stop those.

Is there any evidence suggesting that WS-CART-CS1 is likely to be safe for humans?

Research shows that WS-CART-CS1, a type of CAR-T cell therapy targeting CS1, might be safe and manageable for people with multiple myeloma. Other studies have demonstrated that CAR-T therapies can be safely administered in outpatient settings, allowing patients to avoid overnight hospital stays. This indicates that many patients can tolerate CAR-T treatments well.

Additionally, Elotuzumab, an approved treatment targeting CS1, has already demonstrated benefits for multiple myeloma, providing some confidence in the safety of targeting CS1. However, WS-CART-CS1 remains in the early stages of testing, and researchers are still assessing its safety in humans. Participants should consider this when deciding to join the trial. Consulting with a doctor is essential to determine if this trial is a suitable option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which typically involve chemotherapy, targeted therapies, or stem cell transplants, WS-CART-CS1 is a type of CAR-T cell therapy. This treatment is unique because it uses genetically engineered T-cells to specifically target and destroy myeloma cells. Researchers are excited about WS-CART-CS1 because it offers a highly personalized approach, potentially leading to more effective outcomes by harnessing the body's own immune system to fight the cancer. Additionally, this method may have the advantage of long-lasting effects, as the modified T-cells can persist in the body and continue to fight residual cancer cells.

What evidence suggests that WS-CART-CS1 might be an effective treatment for multiple myeloma?

Research has shown that CS1 is a promising target for treating multiple myeloma (MM) because it is present in most patients with this disease. Elotuzumab, an approved drug targeting CS1, has demonstrated the effectiveness of this approach. CAR-T cell therapy, which uses specially modified immune cells to fight cancer, has already succeeded in treating MM with other targets. In this trial, WS-CART-CS1 aims to specifically target CS1 using this method. Existing CAR-T treatments like ide-cel and cilta-cel have demonstrated success in MM, suggesting that WS-CART-CS1 could also be effective. Early results indicate that targeting CS1 with CAR-T cells could offer a new treatment option for MM patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Armin Ghobadi, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with multiple myeloma, a type of blood cancer. Participants should have tried other treatments that didn't work well enough. They must be healthy enough to undergo the procedure and not have any infections or immune system problems that could make it unsafe.

Inclusion Criteria

Measurable disease meeting specific criteria such as Serum M-protein, Urine M-protein, Serum FLC assay, biopsy-proven plasmacytoma, or Bone marrow plasma cells

Agreement to use adequate contraception for women of childbearing potential and men

My kidney, liver, lungs, and heart are all working well.

Exclusion Criteria

I have been treated with CS1-targeted therapies before.

I do not have any infections or serious conditions that would stop me from receiving treatment.

I received treatment for multiple myeloma less than 14 days before my planned leukapheresis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Pre-treatment

Participants undergo apheresis for WS-CART-CS1 manufacturing and may receive anti-multiple myeloma therapy before lymphodepleting chemotherapy

1-2 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy on days -5, -4, and -3

1 week

Treatment

WS-CART-CS1 infusion occurs three days after the last dose of lymphodepleting chemotherapy

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

15 years

What Are the Treatments Tested in This Trial?

Interventions

• WS-CART-CS1

Trial Overview The trial is testing WS-CART-CS1, a new CAR-T cell therapy targeting CS1 on cancer cells, combined with lymphodepleting chemotherapy which prepares the body for the CAR-T treatment by lowering immune cells.

How Is the Trial Designed?

Group I: Part B Dose Expansion: WS-CART-CS1 Experimental Treatment 2 Interventions

* Undergo apheresis procedure for WS-CART-CS1 manufacturing. * Anti-multiple myeloma therapy may be given after leukapheresis and up to one week prior to the start of lymphodepleting chemotherapy at the discretion of the treating physician. * Lymphodepleting chemotherapy on days -5, -4, and -3. * Three days following the last dose of lymphodepleting chemotherapy (on Day 0), WS-CART-CS1 will be infused. * Part B is the dose expansion portion of the study. The dose of WS-CART-CS1 will be determined in Part A of the study.

Group II: Part A Dose Escalation: WS-CART-CS1 Experimental Treatment 2 Interventions

* Undergo apheresis procedure for WS-CART-CS1 manufacturing. * Anti-multiple myeloma therapy may be given after leukapheresis and up to one week prior to the start of lymphodepleting chemotherapy at the discretion of the treating physician. * Lymphodepleting chemotherapy on days -5, -4, and -3. * Three days following the last dose of lymphodepleting chemotherapy (on Day 0), WS-CART-CS1 will be infused. * Part A is the dose escalation portion of the study with the starting dose of 0.5 x 10\^6 cells/kg of WS-CART-CS1.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Paula C. & Rodger O. Riney Blood Cancer Research

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

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]

In a phase I clinical trial involving 30 multiple myeloma patients, anti-BCMA CAR T cells showed favorable safety with no high-grade cytokine release syndrome and only one case of low-grade neurologic toxicity.

The treatment demonstrated significant efficacy, with 10 out of 15 patients with measurable disease achieving a partial response or better, and 4 patients converting to minimal residual disease-negative complete response, indicating strong antimyeloma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. Garfall, AL., Cohen, AD., Susanibar-Adaniya, SP., et al.[2023]

In a study involving 113 patients with relapsed or refractory multiple myeloma, a single infusion of cilta-cel resulted in a remarkable overall response rate of 97%, with 67% achieving a stringent complete response, indicating its high efficacy in this challenging patient population.

While cilta-cel demonstrated significant therapeutic benefits, it was associated with common hematological adverse events and cytokine release syndrome in 95% of patients, though most cases were manageable, highlighting the importance of monitoring for these effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Berdeja, JG., Madduri, D., Usmani, SZ., et al.[2021]

Targeting the distal V domain of the CS1 protein with CAR-T therapy shows promise for effectively killing myeloma cells in both laboratory and mouse model studies.

Creating a fratricide-resistant version of CAR-T cells by deleting CS1 did not enhance the treatment's effectiveness, indicating that the original CAR-T design remains optimal for targeting myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+CS1 expressing CAR-T cells. O'Neal, J., Ritchey, JK., Cooper, ML., et al.[2023]

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]

Chimeric antigen receptor (CAR)-modified T cell therapy has shown promising efficacy in treating refractory or relapsed multiple myeloma (MM) in both preclinical and clinical studies, indicating a potential new treatment avenue for this incurable disease.

The toxicities associated with CAR-T cell therapy are manageable, suggesting that this innovative approach could be a safe option for patients with MM, especially as research continues to identify effective targets and improve technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapies for multiple myeloma. Wu, C., Zhang, L., Brockman, QR., et al.[2020]

In a study of 21 patients with relapsed and refractory multiple myeloma treated with BCMA-chimeric antigen receptor T cells (CART), 17 patients showed effective responses, including 10 achieving complete remission, indicating a promising efficacy of this treatment.

The treatment was associated with manageable adverse reactions, primarily cytokine release syndrome (CRS), which occurred in 20 patients but was mostly mild (Grade 1 or 2), demonstrating that BCMA-CART can be safely administered with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma]. Zhang, XY., Ding, HY., Gang, DX., et al.[2022]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06185751

Safety and Efficacy of CS1 CAR-T (WS-CART-CS1) in ... The investigators are testing the safety and preliminary anti-myeloma efficacy of WS-CART-CS1, a CAR-T cell therapy targeting CS1. Official Title. Phase 1 Dose- ...

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

CAR‐T cells in the treatment of multiple myeloma The study demonstrated that bispecific CD19-BCMA CAR T cells were feasible, safe, and effective in patients with relapsed or refractory MM.

3. nature.com nature.com/articles/s41408-024-01191-8

CAR-T cell therapy in Multiple Myeloma: current status and ... Updated results after 33 months follow-up reported an impressive median PFS of 34.9 months with an estimated 63% OS at 36 months [28]. In cohort ...

4. ashpublications.org ashpublications.org/blood/article/146/14/1677/537756/Remission-conversion-drives-outcomes-after-CAR-T

Remission conversion drives outcomes after CAR T-cell ... Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19541

Outcomes with non-BCMA CAR T cell therapy for multiple ... At 9 months, Zhang et al. reported a progression-free survival (PFS) of 87.5% (95% CI 38.7-98.1). Conclusions: GPRC5D can be an effective non- ...

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

WS-CART-CS1 for the Treatment of Patients with Recurrent ... Giving WS-CART-CS1 may be safe, tolerable and effective in treating patients with relapsed or refractory multiple myeloma. Eligibility Criteria. Inclusion ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11101341/

CAR T therapies in multiple myeloma: unleashing the future Due to its safety, 25% of the treatments were administered on an outpatient basis. The development of P-BCMA-101 CAR T-cells brings hope for ...