Descartes-08 for Lupus

(SLE-001 Trial)

Overseen By Study Trial Central Mailbox

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cartesian Therapeutics

Must be taking: Glucocorticoids, Immunosuppressives

Disqualifiers: Severe lupus nephritis, Severe CNS lupus, Major chronic illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase II study to evaluate the safety, tolerability and manufacturing feasibility of Descartes-08 CAR T-cells in patients with Systematic Lupus erythematosus (SLE).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since it mentions ongoing immunosuppressive therapy, you might be able to continue some medications. It's best to discuss this with the trial team.

What data supports the effectiveness of the treatment Descartes-08 for Lupus?

Research shows that CAR T cell therapy, which targets specific B cells, has been effective in treating systemic lupus erythematosus (SLE) by reducing disease symptoms and inflammation in patients who did not respond to other treatments. ^{1 2 3 4 5}

Is Descartes-08 generally safe for humans?

Descartes-08, an anti-BCMA CAR-T cell therapy, has been tested for safety in multiple myeloma patients. While it shows promise, there have been reports of severe but reversible neurological side effects, such as in a case where a patient experienced significant neurological complications that resolved with treatment. ^{2 6 7 8 9}

How is the Descartes-08 treatment different from other treatments for lupus?

Descartes-08 is a unique treatment because it uses engineered T cells (a type of immune cell) to target and attack specific cells, and it is designed to limit its activity to a short period, reducing the risk of side effects. This approach is different from traditional lupus treatments, which often involve medications that broadly suppress the immune system. ^{6 7 8 10 11}

Eligibility Criteria

This trial is for adults over 18 with systemic lupus erythematosus (SLE) who still have symptoms despite trying at least two immunosuppressive medications and steroids. They must also have specific autoantibodies present in their blood.

Inclusion Criteria

I have been diagnosed with systemic lupus erythematosus (SLE).

My blood test shows I have specific antibodies related to my condition.

I still have symptoms despite taking steroids and two other immune-suppressing drugs for 3 months.

Exclusion Criteria

Patient is pregnant or lactating

I do not have severe kidney or brain lupus, or major neurological symptoms from lupus.

Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive Descartes-08 CAR T-cells to evaluate safety, tolerability, and manufacturing feasibility

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Descartes-08

Trial Overview The study is testing the safety, how well patients can tolerate, and the production process of a CAR T-cell therapy called Descartes-08 in people with SLE to see if it's feasible as a treatment option.

Participant Groups

Group I: Descartes-08 Experimental Treatment 1 Intervention

Drug: Descartes-08 Autologous T-cells expressing a chimeric antigen receptor directed to BCMA

Descartes-08 is already approved in United States for the following indications:

Approved in United States as Descartes-08 for:

• Generalized Myasthenia Gravis (MG)
• Systemic Lupus Erythematosus (SLE)
• Juvenile Dermatomyositis (JDM)

Who Is Running the Clinical Trial?

Cartesian Therapeutics

Lead Sponsor

Trials

10

Recruited

300+

Findings from Research

CAR T therapy, known for its success in treating blood cancers, has been applied to systemic lupus erythematosus in a small study involving five patients, indicating its potential beyond cancer treatment.

The findings from Mackensen et al. suggest that CAR T therapy could be a promising new approach for autoimmune diseases, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T therapy extends its reach to autoimmune diseases. Baker, DJ., June, CH.[2023]

Using CAR T cells to continuously deplete B cells leads to remission of lupus symptoms in mice that are genetically predisposed to the disease, suggesting a potential therapeutic strategy for lupus.

This study highlights the effectiveness of targeted cell therapy in managing autoimmune diseases, demonstrating that manipulating the immune system can result in significant health improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. Clark, RA.[2019]

Recent advancements in CAR T cell therapy targeting CD19 have shown promising results in treating autoimmune diseases, leading to rapid and sustained depletion of autoreactive B cells.

Patients with refractory systemic lupus erythematosus and dermatomyositis experienced complete clinical and serological remission after treatment with autologous CD19 CAR T cells, highlighting a potential new approach for those who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy in autoimmune diseases. Schett, G., Mackensen, A., Mougiakakos, D.[2023]

In a study of six patients with refractory systemic lupus erythematosus (SLE), anti-CD19 CAR T cell therapy was found to be well tolerated and led to a significant reduction in inflammatory cytokines IL-6 and TNFα three months after treatment.

The therapy also resulted in a marked decrease in SLE-associated antibodies in five out of six patients, suggesting a potential mechanism for its efficacy in managing SLE symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Nunez, D., Patel, D., Volkov, J., et al.[2023]

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

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]

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]

C-CAR088, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 96.4% in patients with relapsed or refractory multiple myeloma, with significant rates of complete response (10.7%) and stringent complete response (46.4%).

The therapy showed a favorable safety profile, with 93.5% of patients experiencing cytokine release syndrome (CRS) that was manageable and reversible, and no dose-limiting toxicities reported across the tested dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Qu, X., An, G., Sui, W., et al.[2022]

BCMA-targeted CAR-T-cell therapy shows high efficacy in treating multiple myeloma, with an overall response rate of 80.5% and a complete response rate of 44.8% across 23 different CAR-T products studied in 640 patients.

Despite significant toxicity, including cytokine release syndrome in 80.3% of patients and neurotoxicity in 10.5%, the therapy offers a median progression-free survival of 12.2 months, which is substantially better than the expected 1.9 months for standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. Roex, G., Timmers, M., Wouters, K., et al.[2021]

APRIL-CAR T cells showed rapid but not long-lasting antitumor responses in mouse models of multiple myeloma, indicating a need for improved strategies to sustain efficacy.

The study revealed that BCMA, the target antigen, was quickly downmodulated and internalized by myeloma cells after CAR T cell interaction, which may contribute to treatment resistance and tumor progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. Camviel, N., Wolf, B., Croce, G., et al.[2022]

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]

References

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

CAR T therapy extends its reach to autoimmune diseases. [2023]

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

Slamming the brakes on lupus with CAR T cells. [2019]

3. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy in autoimmune diseases. [2023]

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

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. [2023]

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

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth. [2020]