Isatuximab in Lung Transplant Recipients

NYU Langone Health

Status and phase: Withdrawn; Early Phase 1

Conditions: Antibody-mediated Rejection; Allosensitization

Treatments: Procedure: bone marrow biopsy; Drug: Isatuximab

Study type: Interventional

Funder types: Other

Identifiers

NCT05862766

22-00992

Details and patient eligibility

About

The purpose of this study is to determine the safety and feasibility of adding isatuximab to standard of care therapies in patients who will receive a lung transplant, but have significant antibodies against the donor (desensitization), or patients who have previously received a lung transplant and develop antibodies against the donor (antibody-mediated rejection, AMR). The study will compare the impact of isatuximab on the recurrence of antibodies after they have been removed from the blood by a process known as plasmapheresis that is standard of care for this condition. The use of isatuximab in lung transplant recipients is investigational, meaning it is not Food and Drug Administration (FDA) approved for use 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 the treatment of multiple myeloma. It may also be useful for transplant recipients with antibodies against the donor because it eliminates the cells that make antibodies.

Full description

This dual-arm pilot study will enroll approximately 6 patients undergoing lung transplantation at NYU Langone Health who are either receiving peri-transplant desensitization, or who are admitted for treatment of AMR. All patients will be treated with standard-of-care consisting of plasmaspheresis, IVIG, and rituximab. Additionally, the experimental agent, isatuximab, will be added to this treatment protocol. The patients will first receive 4 weekly doses of isatuximab, followed by 4 bi¬-weekly doses (total 8 doses given over 12 weeks). 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, patients undergoing peri-transplant desensitization 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.

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Cohort A (Desensitization) Inclusion Criteria:

• Age ≥ 18 years
• 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
• Able and willing to provide informed consent
• 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)

Cohort B (AMR) Inclusion Criteria:

• Age ≥ 18 years
• Received a lung transplant or multi-organ transplant involving a lung at NYU Langone Health
• Able and willing to provide informed consent
• Allograft dysfunction in the setting of at least one of the following criteria:
• Histopathology suggestive of AMR
• Lung biopsy demonstrating C4d deposition
• Positive DSA > 2,000 MFI (as individual DSA MFI)

Exclusion criteria

• Prior or current treatment with rituximab within 6 months of isatuximab administration
• Prior or current treatment with tocilizumab within 6 months of isatuximab administration
• Contraindication to isatuximab due to intolerance or hypersensitivity
• Pregnant or breastfeeding women
• Known malignancy
• Active infection without adequate treatment or source control
• Known hepatitis B viral infection
• Known HIV infection

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Peri-transplant desensitization group

Experimental group

Description:

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:

Drug: Isatuximab

Procedure: bone marrow biopsy

Treatment of antibody-mediated rejection

Experimental group

Description:

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.

Treatment:

Drug: Isatuximab