Anti-BCMA CAR-T Cells for Multiple Myeloma

Overseen By HDFCCC Cancer Immunotherapy Program

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Martin, MD

Must be taking: Proteasome inhibitors, Immunomodulatory therapy, Anti-CD38 antibodies

Must not be taking: Systemic corticosteroids

Disqualifiers: 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 for individuals with relapsed or refractory multiple myeloma, a challenging type of blood cancer. The treatment uses anti-BCMA CAR-T cells, specially designed to locate and attack cancer cells. The primary goal is to assess the treatment's safety for participants. Suitable candidates for this trial have multiple myeloma that has not responded to at least three other treatments, including specific medicines like proteasome inhibitors and immunomodulatory therapies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-multiple myeloma therapy, including systemic corticosteroids, at least 14 days before starting the chemotherapy that prepares you for the CAR-T cell treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that anti-BCMA CAR-T cell therapy is safe for people with multiple myeloma. Studies have found it effective and capable of extending life expectancy. Most patients tolerate the treatment well, experiencing no severe side effects. Serious side effects are rare, and many patients respond positively to the treatment. For those considering joining a trial, these findings suggest that the treatment is generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for multiple myeloma, which typically include chemotherapy, proteasome inhibitors, or immunomodulatory drugs, the anti-BCMA CAR-T cell therapy is a groundbreaking approach that harnesses the power of the patient's own immune system. This treatment involves engineering T cells to specifically target and destroy cancer cells expressing the BCMA protein, a marker found on multiple myeloma cells. Researchers are excited about this therapy because it offers the potential for personalized, targeted treatment with the possibility of producing strong and lasting responses, even in patients who have not responded to other therapies. By directly engaging the immune system, CAR-T cell therapy represents a promising new direction in the fight against this challenging cancer.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that anti-BCMA CAR-T cell therapy for multiple myeloma is promising. In this trial, participants will receive varying doses of anti-BCMA CAR-T cells to identify the most effective and safe dose. Studies have found this treatment to be highly effective, with one study showing a 96.3% response rate in certain high-risk patients. In another study, patients experienced about 9.6 months without cancer progression after treatment. This therapy also improves survival rates and reduces harmful side effects. These findings suggest that anti-BCMA CAR-T cells could be a strong option for treating multiple myeloma that has returned or is not responding to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Thomas Martin, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Multiple Myeloma that's come back or hasn't responded to treatment. They must have tried at least three therapies, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies. Participants need good organ function and can't be pregnant or breastfeeding. People with active CNS issues, autoimmune diseases needing recent treatment, uncontrolled illnesses, another cancer (except certain skin cancers), or active hepatitis B/C are excluded.

Inclusion Criteria

Voluntarily sign informed consent form

I am fully active or can carry out light work.

My organs are working well.

Exclusion Criteria

I haven't used any myeloma treatment or steroids in the last 14 days.

I have another cancer type, but it's either fully treated or not serious.

I do not have active brain conditions like seizures, stroke, or Parkinson's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and CAR-T Cell Manufacturing

Participants undergo apheresis for collection of autologous peripheral blood mononuclear cells to generate CAR-T cells

Up to 21 days

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by 2-5 days of rest

1 week

CAR-T Cell Infusion

A single infusion of anti-BCMA CAR-T cells is administered

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term Follow-up

Participants are followed up annually for up to 15 years to monitor overall survival and long-term effects

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Manufactured Anti-BCMA CAR-T cells

Trial Overview The study tests the safety of anti-BCMA CAR-T cell therapy in those with relapsed/refractory Multiple Myeloma. It involves an open-label design where everyone gets the same experimental treatment after pre-treatment with Cyclophosphamide and Fludarabine to prepare their immune system.

How Is the Trial Designed?

Group I: Dose Expansion: Maximum Tolerated Dose (MTD) Experimental Treatment 3 Interventions

Participants will undergo apheresis with collection of autologous peripheral blood mononuclear cells that will be used to generate CAR-T cells. After successful generation of the anti-BCMA CAR-T cells, and no dose limiting toxicities were reported for the previous dose level, participants will undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by 2-5 days of rest. A single infusion of anti-BCMA CAR-T cells at the MTD will then be given on Day 1.

Group II: Dose Escalation (600 x 10^6 CAR + T cells/ infusion) Experimental Treatment 3 Interventions

Participants will undergo apheresis with collection of autologous peripheral blood mononuclear cells that will be used to generate CAR-T cells. After successful generation of the anti-BCMA CAR-T cells, and no dose limiting toxicities were reported for the previous dose level, participants will undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by 2-5 days of rest. A single infusion of anti-BCMA CAR-T cells at the next highest dose of 600 x 10\^6 flat dose will then be given on Day 1.

Group III: Dose Escalation (450 x 10^6 CAR + T cells/ infusion) Experimental Treatment 3 Interventions

Participants will undergo apheresis with collection of autologous peripheral blood mononuclear cells that will be used to generate CAR-T cells. After successful generation of the anti-BCMA CAR-T cells, and no dose limiting toxicities were reported for the previous dose level, participants will undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by 2-5 days of rest. A single infusion of anti-BCMA CAR-T cells at the next highest dose of 450 x 10\^6 flat dose will then be given on Day 1.

Group IV: Dose Escalation (150 x 10^6 CAR + T cells/ infusion) Experimental Treatment 3 Interventions

Participants will undergo apheresis with collection of autologous peripheral blood mononuclear cells that will be used to generate CAR-T cells. After successful generation of the anti-BCMA CAR-T cells, participants will undergo lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by 2-5 days of rest. A single infusion of anti-BCMA CAR-T cells at the starting dose of 150 x 10\^6 flat dose will then be given on Day 1.

Who Is Running the Clinical Trial?

Thomas Martin, MD

Lead Sponsor

Trials

4

Recruited

130+

University of California, Davis

Collaborator

Trials

958

Recruited

4,816,000+

Eugia Pharma Specialities Limited

Collaborator

Trials

1

Recruited

5+

Actavis Inc.

Industry Sponsor

Trials

99

Recruited

25,200+

Brent Saunders

Actavis Inc.

Chief Executive Officer since 2014

B.A. from the University of Pittsburgh, MBA and J.D. from Temple University

Nesli Basgoz

Actavis Inc.

Chief Medical Officer since 2014

MD from McGill University

Published Research Related to This Trial

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]

BCMA-CAR-T cells, engineered to target the B-cell maturation antigen (BCMA), demonstrated strong cytotoxic effects against BCMA-positive myeloma cells in vitro, significantly reducing the number of residual cancer cells compared to control groups.

In a mouse model of multiple myeloma, treatment with BCMA-CAR-T cells significantly increased survival time, indicating their potential as an effective therapy for patients with BCMA-positive multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells]. Zhong, MJ., Xu, YX., Xing, HY., et al.[2020]

A new BCMA CAR-T cell therapy using the 4C8A monoclonal antibody showed strong and selective binding to BCMA, leading to effective targeting and destruction of multiple myeloma cells in vitro.

In mouse models, BCMA CAR-T cells significantly inhibited tumor formation and caused substantial shrinkage of established tumors, demonstrating their potential efficacy for treating multiple myeloma and supporting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth. Berahovich, R., Zhou, H., Xu, S., et al.[2020]

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]

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]

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 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]

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]

In a study involving 35 patients with relapsed or refractory multiple myeloma, the CAR T-cell therapy ARI0002h achieved a remarkable overall response rate of 100% within the first 100 days, with 80% of patients showing a very good partial response or better.

The treatment demonstrated a favorable safety profile, with 80% of patients experiencing only mild cytokine-release syndrome (grade 1-2) and no neurotoxic events reported, suggesting that ARI0002h could be a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. Oliver-Caldés, A., González-Calle, V., Cabañas, V., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11021094/

Exploring the efficacy and safety of anti-BCMA chimeric ... Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes.

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

CAR-T cell therapy in Multiple Myeloma: current status and ... A phase 1 study, initially in 33 RRMM patients showed promising results which led to development of the phase 2 KarMMa study [13], in which 128 ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/18/4543/537958/Efficacy-and-safety-of-BCMA-nanobody-CAR-T-cell

Efficacy and safety of BCMA nanobody CAR T-cell therapy in ... The results indicated that S103 CAR T-cell therapy was highly effective, particularly in high-risk subgroups. The ORR was 96.3% (26/27), with a ...

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper210451.html

Paper: Efficacy of Anti-BCMA CAR-T Cell Therapies in ... At a median follow-up of 5.1 months after CAR-T infusion, progression-free survival (PFS) across the entire cohort was 9.6 months (0.7-NR) with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525001624007408

Long-term safety and efficacy of the fully human CAR-T ... Of the four patients who received prior anti-BCMA CAR-T cell treatment, two patients achieved sCR and remained in sCR state at the study cutoff.

6. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1149138/full

Effectiveness and safety of anti-BCMA chimeric antigen ... According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety.