CS1-CAR T Therapy for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

Overseen by Myo Htut

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 CS1 positive multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Immune cells can be engineered to kill multiple myeloma cells by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells using a lentiviral vector such as CS1, that allows them to recognize multiple myeloma cells. These engineered immune cells, CS1-CAR T cells, may kill multiple myeloma cells.

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.

What data supports the idea that CS1-CAR T Therapy for Multiple Myeloma is an effective treatment?

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 target and kill multiple myeloma cells, leading to reduced tumor growth in animal models. Additionally, when combined with the drug lenalidomide, the effectiveness of CS1-CAR T cells is enhanced, showing improved immune functions and increased persistence in fighting the cancer. This combination has shown promising results in preclinical trials, suggesting it could be a powerful treatment option for multiple myeloma. Compared to other treatments, CS1-CAR T Therapy offers a targeted approach that can potentially overcome some of the limitations seen with other therapies, such as relapse due to antigen loss. ^{1 2 3 4 5}

What safety data is available for CS1-CAR T Therapy in treating multiple myeloma?

The safety data for CS1-CAR T Therapy in treating multiple myeloma includes findings from various studies. One study on bispecific CS1-BCMA CAR-T cells in relapsed or refractory multiple myeloma patients reported cytokine release syndrome in 38% of patients, with most cases being mild (grade 1-2). No neurological toxicities were observed. Common severe adverse events were hematological, including leukopenia, neutropenia, lymphopenia, and thrombocytopenia. Another consensus report from the European Myeloma Network highlights common adverse events with CAR T-cell therapies, such as cytokine release syndrome, neurotoxicity, cytopenias, and infections, and provides recommendations for their prevention and management. These include premedication, monitoring, corticosteroids, and tocilizumab for cytokine release syndrome, as well as antiviral and antibacterial drugs to prevent infections. ^{1 3 4 6 7}

Is CS1-CAR T Therapy, Cyclophosphamide, and Fludarabine a promising treatment for multiple myeloma?

Yes, CS1-CAR T Therapy is a promising treatment for multiple myeloma. Research shows that it effectively targets and kills myeloma cells, and when combined with other drugs like lenalidomide, it enhances the immune response and improves treatment outcomes. This therapy has shown success in animal studies and provides a strong basis for future clinical trials. ^{1 2 3 4 8}

Research Team

Myo Htut

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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.

You have a disease that can be measured using specific criteria.

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

Treatment Details

Interventions

• CS1-CAR T Therapy (CAR T-cell Therapy)
• Cyclophosphamide (Alkylating agents)
• Fludarabine (Nucleoside Analogues)
• Leukapheresis (Procedure)

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.

Participant Groups

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+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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-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]

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]

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]

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]

References

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

Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma. [2021]

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

Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A compound chimeric antigen receptor strategy for targeting multiple myeloma. [2019]

5. China pubmed.ncbi.nlm.nih.gov

[Eukaryotic expression, protein purification and biological effects research of human CS1-Fc fusion protein]. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. [2023]

7. England 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Recent updates on CAR T clinical trials for multiple myeloma. [2023]