CAR-T Cell Therapy for Multiple Myeloma

(LMY-920-002 Trial)

Overseen By Leland Metheny, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Luminary Therapeutics

Must not be taking: Immunosuppressants, others

Disqualifiers: CNS involvement, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Since CAR-T cell treatment of refractory myeloma has shown success, based on preclinical data, we posit that CAR-T cells expressing B-cell activating factor (BAFF) can become another strategy to treat refractory myeloma, even after relapse following BCMA targeting CAR-T cell treatment. This will be phase 1 study of BAFF ligand CAR-T cells in relapsed and refractory myeloma.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that more than 28 days must have passed since any prior treatment with investigational agents before lymphocyte collection, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the treatment Autologous CAR-T cell therapy expressing the BAFF-ligand for multiple myeloma?

Research shows that BAFF ligand-based CAR-T cells can effectively target and kill multiple B cell cancers, including multiple myeloma, by binding to specific receptors on cancer cells. This suggests potential effectiveness for treating multiple myeloma. ^{1 2 3 4 5}

What safety data exists for CAR-T cell therapy in humans?

CAR-T cell therapy has shown manageable safety concerns, including cytokine-release syndrome (a condition where the immune system releases too many proteins into the blood too quickly), different types of cytopenia (low blood cell counts), infections, and neurotoxicity (nerve damage). Efforts are being made to improve safety, such as incorporating a suicide gene safety system to control the therapy if needed. ^{3 4 6 7 8}

How is the BAFF-ligand CAR-T cell treatment different from other treatments for multiple myeloma?

This treatment is unique because it uses a special type of immune cell called CAR-T cells that are engineered to target three specific receptors (BAFF-R, BCMA, and TACI) on cancer cells, which helps prevent the cancer from escaping treatment. This approach is different from other treatments that typically target only one receptor. ^{1 2 5 6 9}

Research Team

Leland Metheny, MD

Principal Investigator

University Hospitals Seidman Cancer Center

Eligibility Criteria

This trial is for adults over 18 with myeloma that's come back or hasn't responded after at least three treatments, including specific drugs. They must have measurable disease, be in relatively good health (ECOG ≤ 2), and not pregnant or breastfeeding. Participants need functioning major organs and can't have had certain other cancers or heart, lung, liver problems.

Inclusion Criteria

My heart pumps well and I don't have fluid around it.

My oxygen level is 92% or higher without extra oxygen.

I agree to not have sex or use birth control and not donate sperm.

Exclusion Criteria

I have another cancer that needs treatment through the bloodstream.

Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.

I have an autoimmune disease and needed strong medication for it within the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dose-escalation treatment with BAFF ligand CAR-T cells (LMY-920) to determine the maximum tolerated dose

24 months

Follow-up

Participants are monitored for safety, effectiveness, and response rates after treatment

24 months

Treatment Details

Interventions

• Autologous CAR-T cell therapy expressing the BAFF-ligand

Trial Overview The study tests a new CAR-T cell therapy using BAFF-ligand on patients whose myeloma has relapsed or is refractory to treatment. It's an early-phase trial to see how well these modified immune cells work against cancer that didn’t respond to previous therapies like BCMA targeting CAR-T cells.

Participant Groups

Group I: LMY-920 dose escalation Experimental Treatment 1 Intervention

Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.

Who Is Running the Clinical Trial?

Luminary Therapeutics

Lead Sponsor

Trials

3

Recruited

70+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Findings from Research

CAR T cell therapy, originally successful for treating leukemia, is now being explored for multiple myeloma, targeting specific antigens like BCMA and CD138.

Preliminary results from clinical trials indicate that CAR T cell therapy shows promise in treating multiple myeloma, although only a limited number of patients have been treated so far.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs in the Lead Against Multiple Myeloma. Ormhøj, M., Bedoya, F., Frigault, MJ., et al.[2018]

BAFF CAR-T cells, developed using a non-viral gene delivery method, effectively target and kill various B cell cancers, including mantle cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia, both in laboratory settings and in animal models.

These CAR-T cells bind to three different BAFF receptors, which helps reduce the risk of cancer cells escaping treatment by losing the targeted antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. Wong, DP., Roy, NK., Zhang, K., et al.[2023]

In a phase 1 study of 33 patients with relapsed or refractory multiple myeloma, the CAR T-cell therapy bb2121 demonstrated a high objective response rate of 85%, with 45% of patients achieving complete responses.

While bb2121 showed promising antitumor activity, it also had significant safety concerns, with 76% of patients experiencing cytokine release syndrome and 42% experiencing neurological toxic effects, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. Raje, N., Berdeja, J., Lin, Y., et al.[2021]

Chimeric antigen receptor (CAR)-T cell therapy shows promising efficacy and manageable toxicity in heavily pretreated multiple myeloma patients, with over 50 ongoing clinical trials exploring various CAR-T designs and targets.

The most effective CAR-T therapy so far targets B cell maturation antigen, but challenges remain, including the duration of response and the risk of prolonged cytopenia, necessitating further research to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of CAR-T cell therapies for multiple myeloma. Gagelmann, N., Riecken, K., Wolschke, C., et al.[2021]

In a phase II trial involving 69 patients with relapsed or refractory multiple myeloma, the combination of anti-BCMA and anti-CD19 CAR T cells resulted in a high overall response rate of 92%, with 60% achieving a complete response.

The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine release syndrome, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. Wang, Y., Cao, J., Gu, W., et al.[2022]

Chimeric antigen receptor (CAR) T-cell therapy shows great promise for treating relapsed/refractory multiple myeloma (RRMM), building on its success in other blood cancers like acute lymphocytic leukemia and diffuse large B-cell lymphoma.

The review highlights six potential target antigens for CAR T-cell therapy in multiple myeloma and discusses the safety profiles of existing CAR T-cell treatments, indicating a significant advancement in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. Huang, H., Wu, HW., Hu, YX.[2020]

CAR T-cell therapy targeting B-cell maturation antigen (BCMA) has shown promising results in treating multiple myeloma, with high-quality responses observed in heavily pretreated patients, and ongoing Phase 3 trials are comparing its efficacy against standard treatments.

While CAR T-cell therapy can lead to sustained responses in some patients, most eventually relapse due to factors like loss of CAR T cells or antigen expression, prompting research into improving CAR design and safety measures, such as suicide gene systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for multiple myeloma: state of the art and prospects. van de Donk, NWCJ., Usmani, SZ., Yong, K.[2021]

CD229 CAR T cells have shown strong activity against multiple myeloma (MM) plasma cells and related cells in both laboratory and animal studies, suggesting they could be a promising treatment option for this challenging cancer.

Importantly, CD229 CAR T cells do not harm normal T cells during production, as they selectively target MM cells while sparing functional T cells that express low or no CD229, which may enhance safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Radhakrishnan, SV., Luetkens, T., Scherer, SD., et al.[2021]

In a study of five patients with relapsed multiple myeloma receiving anti-BCMA CAR-T cell therapy, four achieved complete remission within one month, indicating strong efficacy of this treatment.

The levels of soluble BCMA (sBCMA) in plasma decreased significantly after CAR-T infusion, suggesting that sBCMA could serve as a useful biomarker for monitoring treatment response in multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma. Seipel, K., Porret, N., Wiedemann, G., et al.[2023]

References

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

CARs in the Lead Against Multiple Myeloma. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. [2023]

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

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. [2021]

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

Development of CAR-T cell therapies for multiple myeloma. [2021]

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

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. [2020]

7. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for multiple myeloma: state of the art and prospects. [2021]

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

CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma. [2023]