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

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I dose-escalation study to evaluate the safety, tolerability and preliminary efficacy of an autologous BCMA-targeting RNA-engineered CAR T-cell therapy in patients with Relapsed/Refractory Multiple Myeloma. The cell product is referred to as Descartes-15

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.

What data supports the effectiveness of the treatment Descartes-15 for multiple myeloma?

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 specific protein (BCMA) on these cancer cells. Clinical trials have demonstrated high response rates, and preclinical studies indicate that similar treatments can significantly inhibit myeloma growth and prolong survival in animal models. ^{1 2 3 4 5}

What is known about the safety of Descartes-15 or similar BCMA CAR-T cell therapies?

BCMA CAR-T cell therapies, like Descartes-15, have shown some safety concerns, including cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurological side effects, but these are often manageable and reversible. In studies, most severe side effects were related to blood cell counts, and no high-grade cytokine release syndrome was observed in some trials. Overall, these therapies have been considered to have a good safety profile in patients with multiple myeloma. ^{5 6 7 8 9}

How is the Descartes-15 treatment different from other treatments for multiple myeloma?

Descartes-15 is unique because it uses mRNA technology to create CAR-T cells that target BCMA, a protein on myeloma cells, and is designed to have a controlled duration of activity, potentially reducing side effects compared to traditional CAR-T therapies. ^{1 4 5 8 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Overview of anti-BCMA CAR-T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma. [2020]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma. [2021]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Switzerland 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. [2021]

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

Safety and Efficacy of BCMA CAR-T Cell Therapy in Older Patients With Multiple Myeloma. [2023]

10. Netherlands 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. [2023]