Cell Therapy for Multiple Myeloma

Not currently recruiting at 5 trial locations

Overseen By Arcellx, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kite, A Gilead Company

Must be taking: Proteosome inhibitors, immunomodulatory drugs

Disqualifiers: Plasma cell leukemia, severe hypersensitivity, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new cell therapies to help people with multiple myeloma, a type of blood cancer, who have not responded to other treatments. The study examines two treatments, ARC-T Plus Anti-BCMA SparX and CART-ddBCMA (also known as anitocabtagene-autoleucel), designed to target and fight cancer cells. It focuses on individuals who have tried at least three different treatment plans and still have active disease. Participants should have multiple myeloma that does not respond to common treatments and be in generally good health otherwise. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

In earlier studies, ARC-T Plus Anti-BCMA SparX has demonstrated a manageable safety profile. Although 95% of patients experienced cytokine release syndrome, a common reaction to this therapy, the side effects were considered manageable. The ARC-SparX platform is designed to control potential side effects by adjusting doses, which can help reduce them.

Research on CART-ddBCMA, another treatment option, suggests it is safe for patients with multiple myeloma. It has shown strong and lasting responses in patients whose disease returned or did not respond to treatment. This treatment also has a 97% overall response rate, with side effects considered acceptable.

Both treatments are still being studied in early-phase trials, so detailed long-term safety data is still being collected. However, the current findings are promising for those considering participation in these trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for multiple myeloma because they harness the power of advanced cell therapy. Unlike traditional treatments like chemotherapy or proteasome inhibitors, ARC-T Plus Anti-BCMA SparX and CART-ddBCMA are engineered T-cell therapies that specifically target the BCMA protein found on myeloma cells. This targeted approach aims to directly attack cancer cells while sparing healthy ones, potentially leading to more effective and less toxic outcomes. Additionally, these therapies represent a personalized approach, as they utilize a patient's own immune cells to combat the disease, which could offer hope for those with relapsed or refractory cases who have limited options.

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

Research has shown that BCMA-targeted CAR T-cell therapies, such as ARC-T Plus Anti-BCMA SparX, effectively treat multiple myeloma, particularly in patients with recurrent cancer. One study found that ARC-T cells, when combined with BCMA SparX, effectively eliminate tumors. In this trial, participants may receive ARC-T Plus Anti-BCMA SparX. Another treatment option is CART-ddBCMA, which achieved a 97% overall response rate in patients with relapsed or hard-to-treat multiple myeloma who have already tried at least three other treatments. Both therapies show great promise for helping patients with difficult-to-treat multiple myeloma. ^{1 4 6 7 8}

Who Is on the Research Team?

Arcellx, Inc.

Principal Investigator

Arcellx, Inc.

Are You a Good Fit for This Trial?

This trial is for people with multiple myeloma who have tried at least three treatments, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies. They should not be severely ill with other conditions or have a history of plasma cell leukemia. Participants need to be relatively healthy otherwise and expected to live more than 12 weeks.

Inclusion Criteria

You have a disease that can be measured and documented.

My multiple myeloma has not responded to 3 types of treatments including PI, IMiD, and CD38mab.

My organs are working well.

Exclusion Criteria

I have or had plasma cell leukemia.

I do not have any severe illnesses or lab results that are out of control.

I cannot take fludarabine or cyclophosphamide due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Phase I study of BCMA-specific CAR-modified T-cell therapy for relapsed and refractory multiple myeloma

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term safety follow-up

Includes long-term safety follow-up for participants

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ARC-T Plus Anti-BCMA SparX
• CART-ddBCMA

Trial Overview The study is testing new cell therapies called ARC-T Plus Anti-BCMA SparX and CART-ddBCMA in patients whose multiple myeloma has come back or hasn't responded after several treatments. It's an early-stage trial to see if these therapies are safe and how they work.

How Is the Trial Designed?

Group I: ARM 1 Experimental Treatment 1 Intervention

Phase I study of BCMA-specific CAR-modified T-cell therapy using alternative binding domain, for the treatment of patients with relapsed and refractory multiple myeloma

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Arcellx, Inc.

Industry Sponsor

Trials

5

Recruited

650+

Published Research Related to This Trial

In a phase I clinical trial involving 30 multiple myeloma patients, anti-BCMA CAR T cells showed favorable safety with no high-grade cytokine release syndrome and only one case of low-grade neurologic toxicity.

The treatment demonstrated significant efficacy, with 10 out of 15 patients with measurable disease achieving a partial response or better, and 4 patients converting to minimal residual disease-negative complete response, indicating strong antimyeloma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. Garfall, AL., Cohen, AD., Susanibar-Adaniya, SP., et al.[2023]

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]

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 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]

The introduction of second-generation proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has significantly improved survival rates for multiple myeloma patients, but many still relapse, highlighting the need for new therapies.

B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy shows promise as a new treatment option for patients with multiple myeloma who are resistant to current standard therapies, offering a different mechanism of action to combat the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. Rodríguez-Otero, P., Prósper, F., Alfonso, A., 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]

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]

BCMA-directed therapies, such as antibody-drug conjugates and CAR T cells, have shown significant effectiveness in treating late-stage myeloma patients who have previously undergone various treatments, but the best order for using these therapies is still unclear.

After anti-BCMA therapy, there are several promising treatment options available, including alternative BCMA therapies and non-BCMA therapies, but more research is needed to personalize treatment strategies based on individual patient factors and disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options at the time of relapse after anti-BCMA therapy. Razzo, B., Garfall, AL., Cohen, AD.[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]

Citations

1. withpower.com withpower.com/trial/phase-1-multiple-myeloma-10-2019-508bc

Cell Therapy for Multiple Myeloma · Info for Participants Research shows that BCMA-targeted CAR T-cell therapies are highly effective in treating multiple myeloma, with high response rates in patients who have relapsed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11184337/

Controlling CAR-T cell activity and specificity with synthetic ... At this dose of bivalent BCMA SparX, the ARC-T cells were able to clear the tumors just as rapidly and to the same extent as the BCMA-CAR (Figures 4C and S4C).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10290473/

Targeting B Cell Maturation Antigen in Patients with ... In this review, we discuss the existing BCMA-targeted therapies and provide insights into currently available treatment and future developments, ...

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

Paper: Efficacy of Anti-BCMA CAR-T Cell Therapies in ... The overall response rate was 62.5% and 85.0% in pts treated with ide-cel (n=16, 41.2% very good partial response or better (≥VGPR)) and cilta- ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/C167337

Clinical Trials Using Anti-BCMA SparX Protein Plus ... NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying anti-bcma sparx protein plus bcma-directed ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1525001624002508

Controlling CAR-T cell activity and specificity with synthetic ... The ARC-SparX platform is designed to expand patient and physician access to cell therapy by controlling potential toxicities through SparX dosing regimens.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10318167/

Effectiveness and safety of anti-BCMA chimeric antigen ... The results of our meta-analysis provide a reference for relapsed or refractory multiple myeloma patient selection for anti-BCMA CAR-T treatment ...

8. onclive.com onclive.com/view/trial-assessing-car-t-cell-therapy-aclx-001-in-relapsed-refractory-multiple-myeloma-begins

Trial Assessing CAR T-Cell Therapy ACLX-001 in ... Investigators have initiated a phase 1 trial exploring ACLX-001, a novel CAR T-cell therapy using the ARC-SparX platform, in patients with relapsed/refractory ...