CC-97540 for Severe Refractory Lupus

Recruiting at76 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Bristol-Myers Squibb

Disqualifiers: Drug-induced SLE, Multiple sclerosis, Psoriasis, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called CC-97540. It aims to help people with severe autoimmune diseases that don't get better with regular treatments. Researchers want to see if the drug is safe, how it moves through the body, and if it can improve patients' health.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have had an inadequate response to certain treatments, which suggests that you may continue some existing medications. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug CC-97540 for treating severe refractory lupus?

Research shows that cyclophosphamide, a component of the treatment, is effective in managing severe lupus, especially lupus nephritis, by improving prognosis and controlling inflammation. Additionally, fludarabine has shown promise in reducing kidney damage in lupus models, suggesting potential benefits for lupus treatment. ^{1 2 3 4 5}

What safety data exists for treatments related to CC-97540 for severe refractory lupus?

Cyclophosphamide, a component of the treatment, is widely used for severe lupus and has been shown to improve outcomes, but it can cause significant side effects, including gonadal toxicity (affecting reproductive organs). Fludarabine, another component, has been studied in mice and showed some positive effects, but human trials are limited, suggesting more research is needed to fully understand its safety. ^{2 3 4 5 6}

How is the drug CC-97540 different from other treatments for severe refractory lupus?

The drug CC-97540, combined with cyclophosphamide and fludarabine, is unique because it targets severe refractory lupus, a condition with limited treatment options. Cyclophosphamide is a standard treatment for severe lupus, while fludarabine has shown promise in reducing kidney damage in lupus models, suggesting a novel combination approach for difficult-to-treat cases. ^{2 3 4 5 7}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for people with severe, hard-to-treat Systemic Lupus Erythematosus (SLE). Participants must meet specific SLE criteria and have active disease in major organs. They should have tried at least two treatments like cyclophosphamide or mycophenolic acid without success.

Inclusion Criteria

My lupus affects specific organs and hasn't improved with several treatments.

I have antibodies linked to autoimmune conditions.

I have been diagnosed with IIM according to the 2017 criteria.

Exclusion Criteria

My inflammatory muscle disease is not active.

Other protocol-defined Inclusion/Exclusion criteria apply

Other systemic autoimmune diseases excluding specific conditions

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CC-97540, CD19-Targeted Nex-T CAR T Cells

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CC-97540 (Other)
• Cyclophosphamide (Alkylating agents)
• Fludarabine (Anti-metabolites)

Trial Overview The study tests the safety, initial effectiveness, and how the body processes CC-97540 in participants with tough SLE cases. It also involves pre-treatment drugs Fludarabine and Cyclophosphamide to prepare the immune system.

Participant Groups

Group I: Administration of CC-97540 Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Lead Sponsor

Trials

19

Recruited

3,100+

Bristol-Myers Squibb Services Unlimited Company

Collaborator

Trials

1

Recruited

130+

Findings from Research

High-dose corticosteroids are the standard initial treatment for severe inflammation in lupus nephritis, but long-term management often requires additional therapies to address underlying immune system issues.

New treatment options for lupus nephritis include novel immunosuppressive agents and combination therapies, which may improve efficacy and reduce toxicity compared to traditional treatments like cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. Balow, JE., Austin, HA.[2019]

In a study using BXSB mice, a model for systemic lupus erythematosus (SLE), treatment with fludarabine resulted in a significant reduction in kidney damage compared to control treatments, suggesting its potential efficacy in managing SLE-related renal pathology.

Fludarabine treatment also led to a notable increase in specific immune cell populations (CD8+CD25+ and CD4+CD25+ T cells), indicating a possible mechanism of action that could enhance immune regulation in SLE, although further research in humans is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of fludarabine treatment on murine lupus nephritis. Jones, OY., Alexander, PJ., Lacson, A., et al.[2023]

Intravenous cyclophosphamide is now the standard treatment for severe systemic lupus erythematosus, especially for cases involving major organs like the kidneys (lupus nephritis).

Newer cytotoxic drugs, such as cyclosporin A and mycophenolate mofetil, show promise in improving lupus management, particularly for patients with less severe forms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indications for, and use of, cytotoxic agents in SLE. Klippel, JH.[2019]

Cyclophosphamide (CY) combined with methyl-prednisolone (MP) is the gold standard treatment for severe lupus nephritis, significantly improving patient prognosis based on randomized controlled trials and long-term studies.

Newer immunosuppressive agents like mycophenolate mofetil (MMF) have shown comparable efficacy to CY with less gonadal toxicity, making them suitable alternatives for moderately severe lupus, while azathioprine and MMF are effective for maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide and lupus nephritis: when, how, for how long? Ntali, S., Bertsias, G., Boumpas, DT.[2021]

High-dose cyclophosphamide (200 mg/kg) can lead to significant reductions in disease activity in patients with severe systemic lupus erythematosus (SLE), as shown by a decrease in average scores from the Systemic Lupus Activity Measure-2 and SLE Disease Activity Index after treatment.

Despite all four patients experiencing febrile neutropenia, there were no long-term complications or deaths, suggesting that high-dose cyclophosphamide may be a safe and effective option for treating severe SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cyclophosphamide for severe systemic lupus erythematosus. Gladstone, DE., Prestrud, AA., Pradhan, A., et al.[2017]

References

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

Progress in the treatment of proliferative lupus nephritis. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Effects of fludarabine treatment on murine lupus nephritis. [2023]

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

Novel approaches to therapy for systemic lupus erythematosus: update 2005. [2010]

4. England pubmed.ncbi.nlm.nih.gov

Indications for, and use of, cytotoxic agents in SLE. [2019]

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

Cyclophosphamide and lupus nephritis: when, how, for how long? [2021]

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

Long-term effects of combination treatment with fludarabine and low-dose pulse cyclophosphamide in patients with lupus nephritis. [2013]

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

High-dose cyclophosphamide for severe systemic lupus erythematosus. [2017]