CAR T-cell Therapy for Multiple Myeloma

Overseen By Koen van Besien, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: David Wald

Must not be taking: Immunosuppressants, others

Disqualifiers: CNS involvement, Active malignancy, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if UF-KURE-BCMA (B-Cell Maturation Antigen) chimeric antigen receptor T cells (CAR-T cells) can be used to treat relapsed or treatment refractory multiple myeloma (RRMM). This treatment uses T cells already present within the body that have been modified outside of the body by a virus and then returned by an infusion to fight cancer. The investigators are evaluating UF-KURE-BCMA because it uses a manufacturing process that is shorter than other Food and Drug Administration (FDA) approved CAR-T cells and only requires a simple blood draw. The standard treatments require weeks to manufacture the cells as well a special procedure to get an individual's cells. While the shorter manufacture time can be an advantage, the safety of this approach has not been demonstrated. The use of UF-KURE-BMCA is investigational and is not approved by the FDA outside of clinical trials. This is the first study of UF-KURE-BCMA in patients. Participants will give a pint of blood, which is the amount one would provide if they were to donate blood. The blood will be used to make the UF-KURE-BCMA cells. Participants will then receive chemotherapy followed by a one-time infusion of the experimental modified CAR-T cells. After this infusion, participants will be watched for side effects and follow up will continue for up to 15 years.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there must be a minimum of 2 weeks since your last radiation or systemic therapy before blood collection for CAR-T manufacturing, unless it was investigational, which requires 4 weeks.

What data supports the effectiveness of the treatment UF-KURE-BCMA CAR-T Cells for multiple myeloma?

Research shows that CAR T-cell therapies targeting BCMA, like UF-KURE-BCMA, have shown strong potential in treating multiple myeloma, with studies reporting high response rates and significant reduction of cancer cells in patients who have tried many other treatments. These therapies have been effective in achieving remission in patients with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for treating multiple myeloma?

CAR T-cell therapy for multiple myeloma has shown a manageable safety profile in clinical trials, with common side effects including cytokine release syndrome (a reaction causing fever and flu-like symptoms) and low blood cell counts. These side effects are generally mild to moderate, and severe neurological issues are rare. ^{6 7 8 9 10}

How is the treatment UF-KURE-BCMA CAR-T Cells different from other treatments for multiple myeloma?

UF-KURE-BCMA CAR-T Cells are unique because they involve genetically modifying a patient's T cells to specifically target and attack multiple myeloma cells by recognizing a protein called BCMA, which is found on these cancer cells. This approach is different from traditional treatments as it uses the body's own immune system to fight the cancer, offering a novel mechanism of action. ^{1 2 3 4 11}

Research Team

Koen van Besien, MD, PhD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for individuals with relapsed or treatment-resistant multiple myeloma. Participants must be able to provide a pint of blood and undergo chemotherapy before receiving the experimental CAR-T cell therapy. Specific inclusion and exclusion criteria details are not provided, but typically involve health status and prior treatments.

Inclusion Criteria

It has been at least 2 weeks since my last cancer treatment before giving blood for CAR-T therapy.

Total bilirubin ≤ 1.52X institutional upper limit of normal

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

My multiple myeloma has spread to my brain.

My tests show early signs of a bone marrow disorder.

I have severe heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-infusion

Multiple myeloma testing, preCAR-T evaluation, and cell collection

1 week

Chemotherapy

Participants undergo lymphodepletion chemotherapy

1 week

CAR-T Cell Infusion

Inpatient CAR T-cell infusion and monitoring for dose limiting toxicity

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Treatment Details

Interventions

• UF-KURE-BCMA CAR-T Cells

Trial Overview The study tests UF-KURE-BCMA CAR-T cells, which are modified T cells designed to target cancer in patients with multiple myeloma. The process involves taking a patient's blood, modifying the T cells outside the body, then infusing them back into the patient after chemotherapy.

Participant Groups

Group I: UF-KURE-BCMA T cell-based immunotherapy Experimental Treatment 3 Interventions

Pre-infusion will include multiple myeloma testing, preCAR-T evaluation, and cells will be collected. Participants will undergo lymphodepletion and inpatient CAR T-cell infusion. Patients will be monitored closely during a 28 day dose limiting toxicity (DLT) period.

Who Is Running the Clinical Trial?

David Wald

Lead Sponsor

Trials

3

Recruited

40+

Findings from Research

B-cell maturation antigen (BCMA) CAR T cells are emerging as a highly effective treatment for multiple myeloma, showing promise for inclusion in first-line therapy based on clinical and preclinical data.

Advancements in patient stratification through genomic analysis and improvements in CAR T-cell manufacturing are enhancing early diagnosis, management of side effects, and overall access to this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? Rasche, L., Hudecek, M., Einsele, H.[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]

In a first-in-humans clinical trial involving 16 patients with heavily treated multiple myeloma, CAR-BCMA T cells demonstrated an impressive overall response rate of 81%, with 63% achieving very good partial or complete responses.

The treatment was associated with significant anti-myeloma activity, including eradication of bone marrow myeloma and resolution of soft-tissue plasmacytomas, although some patients experienced severe but reversible cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. Brudno, JN., Maric, I., Hartman, SD., et al.[2019]

Chimeric antigen receptor T cells targeting the BCMA protein show promise as a potent treatment for multiple myeloma, based on preliminary results from an ongoing phase I clinical trial in China.

The therapy was well tolerated by patients and led to complete and durable responses in those with relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sending CAR T Cells After Multiple Myeloma. [2018]

Anti-BCMA CAR T cells derived from healthy donors showed better T-cell fitness and cytotoxic activity against multiple myeloma cells compared to those derived from patients, indicating a potential advantage in using allogeneic T cells for treatment.

The study demonstrated that these healthy donor-derived CAR T cells could effectively kill primary multiple myeloma cells in the bone marrow microenvironment, suggesting they could be a promising therapeutic strategy for relapsed multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Anti-BCMA CAR T Cells Are Superior to Multiple Myeloma-derived CAR T Cells in Preclinical Studies and May Be Combined with Gamma Secretase Inhibitors. Metelo, AM., Jozwik, A., Luong, LA., et al.[2023]

CAR T-cell therapy, specifically BCMA-directed products like idecabtagene vicleucel and ciltacabtagene autoleucel, has been FDA-approved for treating relapsed/refractory multiple myeloma, showing high response rates in patients who have undergone extensive prior treatments.

Despite their effectiveness, these therapies are associated with significant immune-related side effects and relapse rates, highlighting the need for ongoing research to enhance their efficacy and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review. Sadek, NL., Costa, BA., Nath, K., et al.[2023]

The newly developed BCMA-targeted fourth-generation CAR-T cells (BCMA-7 × 19 CAR-T cells) showed enhanced capabilities in expanding, differentiating, migrating, and killing cancer cells compared to previous CAR-T therapies, indicating improved efficacy against refractory/relapsed multiple myeloma (R/R MM).

In a first-in-human clinical trial involving two patients, BCMA-7 × 19 CAR-T cells demonstrated promising safety and efficacy, with one patient achieving complete remission (CR) and the other a very good partial response (VGPR) after just one dose, and only mild cytokine release syndrome observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. Duan, D., Wang, K., Wei, C., 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]

BCMA CAR T-cell therapy has shown impressive response rates of 60% to 100% in patients with relapsed/refractory myeloma, indicating its potential as a highly effective treatment option.

While the therapy can lead to severe but reversible toxicities like cytokine release syndrome and neurotoxicity, ongoing studies aim to enhance its safety and efficacy through combinations with other treatments and gene editing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. Cohen, AD.[2019]

KITE-585, an autologous CAR T-cell therapy targeting BCMA, showed a manageable safety profile in a phase 1 study with 14 patients, where no dose-limiting toxicities were observed and all patients experienced at least one grade ≥ 3 treatment-emergent adverse event.

Despite the safety, KITE-585 demonstrated limited efficacy, with only one patient achieving a partial response and low levels of CAR T-cell expansion and associated cytokines, indicating minimal anti-tumor activity in relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. Cornell, RF., Bishop, MR., Kumar, S., et al.[2022]

References

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

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? [2023]

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

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

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

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. [2019]

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

Sending CAR T Cells After Multiple Myeloma. [2018]

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

Allogeneic Anti-BCMA CAR T Cells Are Superior to Multiple Myeloma-derived CAR T Cells in Preclinical Studies and May Be Combined with Gamma Secretase Inhibitors. [2023]

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

CAR T-Cell Therapy for Multiple Myeloma: A Clinical Practice-Oriented Review. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. [2021]

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

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

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

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. [2019]

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

A phase 1, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

CAR T cell therapies for patients with multiple myeloma. [2021]