Isatuximab for Antibody-Mediated Rejection

Overseen By Tyler Lewis, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: NYU Langone Health

Must not be taking: Rituximab, Tocilizumab

Disqualifiers: Pregnancy, Malignancy, Active infection, others

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

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

Trial Summary

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 have been treated with rituximab or tocilizumab within 6 months before starting isatuximab.

How does the drug Isatuximab differ from other treatments for antibody-mediated rejection?

Isatuximab is unique because it targets CD38, a protein found on the surface of certain immune cells, which is different from other treatments like rituximab that target CD20. This different mechanism of action may offer a novel approach to treating antibody-mediated rejection, especially in cases where other treatments have not been effective. ^{1 2 3 4 5}

What is the purpose of this trial?

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.

Research Team

Luis Angel, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

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.

Inclusion Criteria

Cohort A (Desensitization) Inclusion Criteria:

I am listed for a lung or multi-organ transplant at NYU Langone Health and need special treatment before the transplant.

Pre-transplant DSA > 5,000 MFI in undiluted serum (measured as individual DSA MFI or as sum of multiple DSAs >1000 MFI in the undiluted serum)

Exclusion Criteria

I have been diagnosed with cancer.

Pregnant or breastfeeding women

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard-of-care treatment with plasmapheresis, IVIG, rituximab, and the experimental agent isatuximab. Isatuximab is administered in 4 weekly doses followed by 4 bi-weekly doses over 12 weeks.

12 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including weekly DSA assessment and flow cytometry crossmatch in the desensitization arm.

4 weeks

Treatment Details

Interventions

• Bone Marrow Biopsy
• Isatuximab

Trial Overview 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.

Participant Groups

Group I: Treatment of antibody-mediated rejection Experimental Treatment 1 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 group Experimental Treatment 2 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

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

Intravenous immunoglobulin (IVIG) combined with rituximab has been shown to effectively reduce anti-HLA antibodies, improving transplantation success rates for highly sensitized patients who were previously considered poor candidates.

The combination therapy also provides a strong anti-inflammatory effect, which is beneficial in treating antibody-mediated rejection, and advancements in detection methods allow for earlier intervention to prevent allograft loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic strategies in management of the highly HLA-sensitized and ABO-incompatible transplant recipients. Jordan, SC., Peng, A., Vo, AA.[2015]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of acute cellular rejection of renal allograft with CD20-positive clusters in the infiltrate. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic strategies in management of the highly HLA-sensitized and ABO-incompatible transplant recipients. [2015]

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

Treatment With the Combination of Rituximab and Intravenous γ Globulin Is Effective in Promoting Engraftment in Donor-Specific Antibody Positive Patients Receiving Myeloablative Conditioning Haploidentical Stem Cell Transplantation. [2023]

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

Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report. [2019]

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

Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab. [2015]