Descartes-15 for Multiple Myeloma

(DC15-MM-01 Trial)

Overseen By Study Trial Central Mailbox

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cartesian Therapeutics

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Infection, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Descartes-15 for individuals with relapsed or refractory multiple myeloma, a type of blood cancer unresponsive to previous treatments. The trial aims to assess the safety and effectiveness of this therapy using specially engineered cells to target the cancer. Participants will be divided into groups to receive different dosing methods, with some undergoing an additional pre-treatment process called lymphodepletion. This trial suits those who have tried at least three other therapies without success. As a Phase 1 trial, the 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 does not specify if you need to stop taking your current medications, but you cannot be on chronic immunosuppressants like cyclosporine or high doses of steroids.

Is there any evidence suggesting that Descartes-15 is likely to be safe for humans?

Research has shown that anti-BCMA CAR T-cell therapy for multiple myeloma (MM) is generally safe and effective. Studies have found it reduces negative outcomes and improves survival rates. This suggests that Descartes-15, which uses similar technology, might also be safe.

Descartes-15 has demonstrated significant improvement in effectiveness compared to earlier versions, such as Descartes-08. This could mean it targets cancer cells more precisely, possibly resulting in fewer side effects. However, since this study remains in its early stages, there is limited information on side effects or safety.

In summary, Descartes-15 appears promising based on the safety records of similar treatments, but further research is needed for confirmation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for multiple myeloma, like chemotherapy and targeted therapy, work by killing cancer cells directly or blocking signals that help them grow. But Descartes-15 stands out because it is a cell therapy that specifically targets the cancer cells without needing lymphodepletion, a process that wipes out certain immune cells beforehand. This makes it potentially less harsh on the patient's immune system. Researchers are excited because Descartes-15, especially the version without lymphodepletion, could offer a more precise and gentler approach to tackling multiple myeloma, which might mean fewer side effects and a better quality of life for patients.

What evidence suggests that Descartes-15 might be an effective treatment for Multiple Myeloma?

Research has shown that anti-BCMA CAR T-cell therapies, such as Descartes-15, effectively find and destroy multiple myeloma cells by recognizing a specific protein on these cancer cells. Studies have demonstrated that this method significantly reduces negative outcomes and improves survival rates in patients with multiple myeloma. In this trial, participants will receive Descartes-15, either with or without lymphodepletion, to assess its effectiveness and safety. Descartes-15 is designed to locate and eliminate myeloma cells by harnessing the body's own defense system. Previous patients have experienced promising results, with better response rates and manageable side effects. This innovative treatment could offer new hope for those facing relapsed or difficult-to-treat multiple myeloma. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for people with Multiple Myeloma that has come back or hasn't responded to treatment. Specific details on who can join are not provided, but typically participants need to meet certain health standards and have a history of the condition being studied.

Inclusion Criteria

My multiple myeloma has returned or is not responding to treatment and can be measured.

I have tried 3 treatments for myeloma, including immunotherapy, proteasome inhibitor, and anti-CD38.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I am currently on high-dose steroids or other drugs that suppress my immune system.

I have an active brain or spinal cord disease.

I do not have any active and uncontrolled infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Descartes-15 infusions with or without lymphodepletion, with dose escalation over six infusions

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Descartes-15

Trial Overview The study is testing Descartes-15, an advanced CAR T-cell therapy designed to target BCMA on myeloma cells. It's in Phase I where they start with low doses and gradually increase them to find the safest and most effective dose.

How Is the Trial Designed?

Group I: Part 2 Arm 2 Descartes-15 without lymphodepletion Experimental Treatment 1 Intervention

Descartes-15 infusions at the maximum tolerated dose level from Part 1. Patients will not receive lymphodepletion prior to initiating cell therapy.

Group II: Part 2 Arm 1 Descartes-15 with lymphodepletion Experimental Treatment 1 Intervention

Descartes-15 infusions at the maximum tolerated dose level from Part 1. Patients will receive lymphodepletion prior to initiating cell therapy.

Group III: Part 1 Descartes-15 with lymphodepletion Experimental Treatment 1 Intervention

Intra-patient dose escalation arm with three dose levels over the course of six infusions of cell product. Patients will receive lymphodepletion prior to initiating cell therapy.

Who Is Running the Clinical Trial?

Cartesian Therapeutics

Lead Sponsor

Trials

10

Recruited

300+

Published Research Related to This Trial

Anti-BCMA CAR-T therapy is a promising new treatment for multiple myeloma (MM) and relapsed/refractory multiple myeloma (RRMM), specifically targeting the B cell maturation antigen (BCMA) on malignant plasma cells, leading to high response rates in clinical trials.

Despite the effectiveness of anti-BCMA CAR-T therapy, there is a need for ongoing research into its side effects and how it compares to other CAR-T therapies to ensure patient safety and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of anti-BCMA CAR-T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma. Feng, D., Sun, J.[2020]

In a study of 83 multiple myeloma patients receiving BCMA CAR-T therapy, older patients (aged ≥70) did not experience significantly higher rates of common toxicities like cytokine release syndrome (CRS) or neurotoxicity compared to younger patients, suggesting that CAR-T therapy is safe for older populations.

Despite older patients having a median overall survival (OS) that was not reached compared to 31.4 months in younger patients, age was not a significant predictor of OS when accounting for other health factors, indicating that BCMA CAR-T therapy remains an effective treatment option for older patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of BCMA CAR-T Cell Therapy in Older Patients With Multiple Myeloma. Reyes, KR., Huang, CY., Lo, M., et al.[2023]

A 56-year-old male with refractory isolated CNS-MM was treated with BCMA-CART therapy, which led to a partial response sustained for 5.5 months, indicating potential efficacy for this rare condition.

The treatment caused severe neurological complications, but these were reversible with intravenous methylprednisolone, highlighting the need for careful monitoring of side effects in BCMA-CART therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Reversible Neurotoxicity and a Clinical Response Induced by BCMA-Directed Chimeric Antigen Receptor T Cells Against Multiple Myeloma With Central Nervous System Involvement. Zhang, Y., Zhang, C., Zhou, J., et al.[2021]

Anti-BCMA CAR-T therapy shows a high overall response rate of 93% in older adults (≥65 years) with relapsed/refractory multiple myeloma, which is comparable to the 86% response rate in younger patients, based on a systematic review of 14 studies involving 558 patients.

While older adults experience similar efficacy to younger patients, they have higher rates of immune cell-effector-associated neurotoxicity syndrome (ICANS) at 15%, indicating a need for careful monitoring of neurotoxicity in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of anti-BCMA CAR-T cell therapy in older adults with multiple myeloma: A systematic review and meta-analysis. Akhtar, OS., Sheeba, BA., Azad, F., et al.[2023]

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]

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]

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]

The study developed novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells that specifically target multiple myeloma cells, showing effective tumor cell killing in laboratory tests and in live models.

These CAR-T cells not only killed multiple myeloma cells but also secreted IFN-gamma, indicating a strong immune response, and they successfully inhibited tumor growth in vivo, paving the way for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma. Golubovskaya, V., Zhou, H., Li, F., et al.[2021]

The novel CD8+ CAR T-cell therapy, Descartes-08, shows promise for treating multiple myeloma by limiting the duration of CAR expression to one week, which helps prevent uncontrolled cell proliferation while maintaining effective cytolytic activity against myeloma cells.

In preclinical mouse models, Descartes-08 significantly inhibited myeloma growth and improved survival rates, and ongoing clinical trials are showing preliminary durable responses, paving the way for further testing in newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma. Lin, L., Cho, SF., Xing, L., et al.[2021]

The introduction of monoclonal antibodies targeting CD38 and SLAMF7 has significantly improved outcomes for patients with relapsed and refractory multiple myeloma (RRMM), but their use may be limited due to expression on normal tissues.

B cell maturation antigen (BCMA) is a promising target for immunotherapy in multiple myeloma, as it is highly expressed on malignant cells but minimally on normal tissues, leading to the development of effective CAR T-cell therapies and antibody-drug conjugates that have shown significant clinical responses in heavily pre-treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy. Cho, SF., Anderson, KC., Tai, YT.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06304636

NCT06304636 | Descartes-15 for Patients With Relapsed/ ... A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved ...

2. 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.

3. withpower.com withpower.com/trial/phase-1-refractory-multiple-myeloma-2-2024-6fa9e

Descartes-15 for Multiple Myeloma (DC15-MM-01 Trial) Research shows that anti-BCMA CAR-T cell therapies, like Descartes-15, have been effective in targeting and killing multiple myeloma cells by recognizing a ...

4. nature.com nature.com/articles/s41417-024-00750-2

CAR T therapies in multiple myeloma: unleashing the future Immunotherapy, particularly CAR T-cell therapy, emerges as a promising frontier in the ongoing pursuit of effective multiple myeloma treatment.

5. cgtlive.com cgtlive.com/view/cartesian-therapeutics-doses-first-patient-mrna-car-t-descartes-15-trial-multiple-myeloma

Cartesian Therapeutics Doses First Patient With mRNA ... Pending the results of the trial, Cartesian plans to eventually evaluate Descartes-15 for the treatment of autoimmune diseases.

6. ir.cartesiantherapeutics.com ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-first-patient-dosed-first-human

Cartesian Therapeutics Announces First Patient Dosed in ... Descartes-15 observed to achieve an approximately ten-fold increase relative to Descartes-08 in CAR expression and selective target-specific ...