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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether isatuximab (Sarclisa) can safely assist lung transplant patients facing antibody attacks on the donor lung. It examines two groups: those needing antibody control before their transplant and those who develop antibody issues afterward. Researchers aim to determine if adding isatuximab to standard treatments like plasmapheresis (a blood-cleaning process) can reduce antibody problems. Individuals who have undergone a lung transplant at NYU Langone Health and are experiencing these antibody challenges might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how isatuximab works in people, offering participants a chance to contribute to groundbreaking medical knowledge.

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.

Is there any evidence suggesting that isatuximab is likely to be safe for humans?

Research has shown that isatuximab is generally safe for patients. In studies involving individuals awaiting kidney transplants, isatuximab demonstrated safety, with no major safety issues reported. The treatment effectively lowered certain antibodies that can cause problems after a transplant. The FDA has also approved isatuximab for treating multiple myeloma, a type of blood cancer, indicating it has undergone safety testing in humans.

Although data on isatuximab for lung transplant patients remains limited, its approval for multiple myeloma and research in kidney transplants provide some confidence in its safety. However, as this is an early phase study, the primary goal is to ensure the treatment's safety for lung transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for antibody-mediated rejection, which includes plasmapheresis, IVIG, and rituximab, isatuximab offers a new approach by specifically targeting CD38 on plasma cells. This mechanism is particularly exciting because it directly aims to eliminate the cells responsible for producing harmful antibodies, potentially reducing rejection rates more effectively. Researchers are optimistic because this targeted action could lead to better outcomes for transplant patients by addressing the root cause of antibody-mediated rejection more precisely.

What evidence suggests that isatuximab might be an effective treatment for antibody-mediated rejection?

Research shows that isatuximab, a drug approved for treating multiple myeloma, might assist lung transplant patients by targeting cells that produce antibodies. In this trial, participants in both the "Treatment of antibody-mediated rejection" and "Peri-transplant desensitization" groups will receive isatuximab alongside standard-of-care treatments. In kidney transplant patients, treatments like isatuximab have effectively managed rejection caused by antibodies. For instance, some studies have shown a response rate of about 23.8%, with some patients experiencing a complete response. Isatuximab removes the cells that create harmful antibodies, which is crucial for patients facing rejection. Although specific data for lung transplants is limited, early results from similar conditions are encouraging. ^{1 3 5 6 7}

Who Is on the Research Team?

Luis Angel, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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.

Cohort B (AMR) Inclusion Criteria:

Exclusion Criteria

Pregnant or breastfeeding women

I have been diagnosed with cancer.

I am HIV positive.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04294459

Study Details | NCT04294459 | Safety, Pharmacokinetics, ... To assess the overall efficacy of isatuximab in desensitization of participants awaiting kidney transplantation. Detailed Description. The study had a screening ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12119314/

Targeting CD38 in Antibody-Mediated Rejection - PMC This review focuses on recent results from CD38-targeted therapies, with felzartamab emerging as a promising option.

3. amjtransplant.org amjtransplant.org/article/S1600-6135(25)02027-1/fulltext

Safety and Efficacy of Anti-CD38 Therapy (Isatuximab) for ... Results: Four patients met the criteria for treatment with isatuximab in 3 months. The mean GFR prior to Isatuximab infusions was 40 ml/min/1.73m2. Median ...

4. academic.oup.com academic.oup.com/ckj/advance-article/doi/10.1093/ckj/sfaf283/8251674

One tool, multiple gains: anti-CD38 therapy in antibody ... Antibody-mediated rejection (AMR) remains a challenge in kidney ... Emerging clinical data suggest promising efficacy with an ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6953105/

Therapeutic Opportunities with Pharmacological Inhibition of ... In patients receiving isatuximab ≥10 mg/kg, the overall response rate (ORR) was 23.8%, including one complete response. In high-risk patients treated with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05862766?term=ISATUXIMAB&viewType=Table&rank=9

NCT05862766 | Isatuximab in Lung Transplant Recipients This study is a pilot study investigating the feasibility and safety of isatuximab in lung transplant patients. Isatuximab is an FDA approved drug indicated for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10914196/

Isatuximab Monotherapy for Desensitization in Highly ... This study shows that isatuximab, a CD38-targeting therapy, was well tolerated in kidney transplant candidates, with a durable decrease in anti-HLA antibodies.