What side effects are associated with this type of intervention?

Common treatments for Antibody Mediated Rejection (AMR) include plasmapheresis, intravenous immunoglobulin (IVIG), and monoclonal antibodies such as rituximab and isatuximab. Plasmapheresis can cause side effects like hypotension, infection, and bleeding. IVIG may lead to headaches, fever, chills, and allergic reactions. Rituximab and isatuximab, which target and eliminate antibody-producing cells, can cause infusion reactions, neutropenia, and increased risk of infections. Specifically, isatuximab has been associated with higher rates of neutropenia and respiratory infections, including pneumonia.

What prior FDA approvals exist?

Rituximab, an FDA-approved drug, is commonly used for the treatment of Antibody Mediated Rejection (AMR) in transplant patients. It targets CD20 on B cells, thereby reducing the production of antibodies. Other drugs like cyclophosphamide and plasmapheresis are also used in managing AMR, but they do not specifically target antibody-producing cells in the same way as rituximab or isatuximab.

What other types of research exist?

Promising alternatives to Isatuximab for AMR patients include: <ol> <li>Rituximab: A monoclonal antibody targeting CD20 on B cells, used to deplete antibody-producing cells.</li> <li></li> </ol> Bortezomib: A proteasome inhibitor that induces apoptosis in plasma cells. 3. Eculizumab: A complement inhibitor that prevents antibody-mediated damage. 4. Tocilizumab: An IL-6 receptor antagonist that modulates the immune response. 5. Belatacept: A fusion protein that inhibits T-cell activation by blocking CD80/CD86. These therapies are either currently used or under investigation for their efficacy in managing AMR.

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Isatuximab for Antibody-Mediated Rejection

Q: What is the mechanism of action of this treatment?

The most common treatments for Antibody Mediated Rejection (AMR) include plasmapheresis, immunosuppressive therapies, and monoclonal antibodies. Plasmapheresis removes circulating antibodies from the blood, reducing their ability to attack the transplanted organ. Immunosuppressive therapies like cyclophosphamide and corticosteroids suppress the immune system, decreasing the production of harmful antibodies. Monoclonal antibodies such as rituximab and isatuximab target and eliminate B cells, the cells responsible for producing antibodies. These treatments are crucial for AMR patients as they help prevent and manage rejection episodes, thereby improving graft survival and patient outcomes.

Phase < 1

Waitlist Available

Led By Luis Angel, MD

Research Sponsored by NYU Langone Health

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 0 (visit 1), day 14 (visit 3), day 28 (visit 5), day 56 (visit 7), day 84 (visit 9)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if adding isatuximab to standard treatments can help lung transplant patients who have harmful antibodies. Isatuximab works by removing the cells that make these antibodies. The study aims to see if this approach is safe and effective.

Who is the study for?

This trial is for adults over 18 who are set to receive or have received a lung transplant at NYU Langone Health and need desensitization due to high antibody levels against the donor, or those with signs of antibody-mediated rejection. Participants must consent and meet specific criteria related to antibodies measured in their blood.

What is being tested?

The study tests the safety and effectiveness of adding isatuximab—a drug approved for multiple myeloma—to standard treatments for patients undergoing lung transplants with significant donor-specific antibodies, either before or after surgery.

What are the potential side effects?

As an investigational treatment in this context, side effects may include reactions similar to other antibody therapies such as infusion-related symptoms, potential impact on immune response, and possible interactions with standard post-transplant care.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 0 (visit 1), day 14 (visit 3), day 28 (visit 5), day 56 (visit 7), day 84 (visit 9)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 0 (visit 1), day 14 (visit 3), day 28 (visit 5), day 56 (visit 7), day 84 (visit 9)

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 0 (visit 1), day 14 (visit 3), day 28 (visit 5), day 56 (visit 7), day 84 (visit 9) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)

Clinical Resolution, as measured by the number of participants with no presence of Donor-specific antibody (DSA)

Clinical Resolution, as measured by the number of participants with reduction of DSA titer

Secondary study objectives

Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with 2001-7999 Mean fluorescent intensity (MFI) at 1:16 dilution

Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with <2000 Mean fluorescent intensity (MFI) at 1:16 dilution

Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) ≥ 8000 Mean fluorescent intensity (MFI) at 1:16 dilution

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Treatment of antibody-mediated rejectionExperimental Treatment1 Intervention

Received a lung transplant or multi-organ transplant involving a lung at NYU Langone Health. Participants will be treated with standard-of-care consisting of plasmaspheresis, IVIG, rituximab and the experimental agent, isatuximab.

Group II: Peri-transplant desensitization groupExperimental Treatment2 Interventions

Listed and will receive a lung transplant or multi-organ transplant involving a lung at NYU Langone Health that is deemed to require peri-transplant desensitization. Participants will be treated with standard-of-care consisting of plasmaspheresis, IVIG, rituximab and the experimental agent, isatuximab. Patients will be followed with standard-of-care immunologic assessment consisting of weekly DSA assessment and flow cytometry crossmatch (only in the desensitization arm). Additionally, participants will have a bone marrow biopsy with pathologic examination and cell counts performed at the time of transplant and repeated at the 30-day bronchoscopy to assess for plasma cell elimination

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Isatuximab

2016

Completed Phase 3

~370

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Antibody Mediated Rejection (AMR) include plasmapheresis, immunosuppressive therapies, and monoclonal antibodies. Plasmapheresis removes circulating antibodies from the blood, reducing their ability to attack the transplanted organ. Immunosuppressive therapies like cyclophosphamide and corticosteroids suppress the immune system, decreasing the production of harmful antibodies. Monoclonal antibodies such as rituximab and isatuximab target and eliminate B cells, the cells responsible for producing antibodies. These treatments are crucial for AMR patients as they help prevent and manage rejection episodes, thereby improving graft survival and patient outcomes.