CAR T-cell Therapy for Multiple Myeloma

Overseen By James Ignatz-Hoover, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called UF-KURE-BCMA CAR-T cells for individuals with multiple myeloma, a type of blood cancer that has returned or is unresponsive to other treatments. The treatment involves taking a person's own immune cells, modifying them in a lab, and then reintroducing them into the body to target cancer cells. Researchers hope this process, which requires only a simple blood draw and less waiting time, will prove safe and effective. Individuals whose multiple myeloma has not responded to at least three different 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 participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that UF-KURE-BCMA CAR-T cells are likely to be safe for humans?

Research has shown that BCMA CAR-T cell therapy is generally safe for treating relapsed or refractory multiple myeloma, based on data from several studies. Most patients tolerated the treatment well. UF-KURE-BCMA is a new version of this therapy, and specific safety data for it is not yet available. As this trial is in its early stages, the primary goal is to assess its safety. Early trials like this focus on safety to understand and manage any side effects. Participants will undergo close monitoring for any side effects, which is a standard part of the process. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about UF-KURE-BCMA CAR-T cells for multiple myeloma because they offer a novel approach compared to standard treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Unlike these traditional options, CAR T-cell therapy involves reprogramming a patient’s own immune cells to specifically target and destroy cancer cells. This personalized method not only holds the potential for more effective targeting of cancer cells but also aims to provide lasting remission by leveraging the body's immune system. Additionally, CAR-T therapy can show rapid results, potentially offering quicker relief than some existing therapies.

What evidence suggests that UF-KURE-BCMA CAR-T cells might be an effective treatment for multiple myeloma?

Research has shown that CAR T-cell therapies targeting BCMA, such as UF-KURE-BCMA, hold strong potential for treating multiple myeloma. In this trial, participants will receive UF-KURE-BCMA T cell-based immunotherapy. Studies indicate that similar BCMA CAR-T treatments have achieved high success rates in patients whose disease has returned or resisted other treatments. For instance, some studies found that nearly all patients responded to treatment, with many experiencing a significant reduction in cancer. UF-KURE-BCMA is promising because it uses a quicker manufacturing process, potentially increasing treatment availability. The therapy works by modifying T cells (a type of immune cell) to better locate and attack cancer cells. Although this method is new, early results from similar treatments suggest it could be effective. ^{1 3 5 6 7}

Who Is on the Research Team?

James Ignatz-Hoover, MD, PhD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06698744

UF-KURE-BCMA CAR-T Cells in Patients With Relapsed or ... 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 ...

2. withpower.com withpower.com/trial/car-t-cell-therapy-for-multiple-myeloma-c50b8

CAR T-cell Therapy 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 ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4848/505708/Development-and-Clinical-Validation-of-an-Ultra

Development and Clinical Validation of an Ultra-Fast CAR-T ... UF-Kure19 cells expanded robustly in the patient and peaked around day 10 (23% of circulating CD3) with a strong skewing of CD4/CD8 cells (93% ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9150173/

Clinical Outcomes of BCMA CAR-T Cells in a Multiple ... A phase 1b/2 study of Cilta-cel reported more amazing data and showed 97% of overall response rate, 67% of stringent complete response, and 77% of 12-month ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-10166

Genetically Modified T Cells (UF-KURE-BCMA CAR-T ... This phase I trial studies the side effects and best dose of UF-KURE-BCMA chimeric antigen receptor (CAR)-T cells in treating patients with multiple myeloma.

6. myeloma.org myeloma.org/sparkcures/trial/2039/description

UF-KURE-BCMA CAR-T Cells A Phase 1 Single Arm, Open Label Study to Evaluate the Safety of UF-KURE-BCMA CAR-T Cells in Patients with Relapsed or Refractory Multiple Myeloma. Overview ...

7. synapse.patsnap.com synapse.patsnap.com/drug/327616c82ce9451c89598fac9f311322

UF-KURE-BCMA CAR-T Cells(The Case Comprehensive ... A Phase 1 Single Arm, Open Label Study to Evaluate the Safety of UF-KURE-BCMA CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma.