Isatuximab in Lung Transplant Recipients

NCT05862766 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 22-00992
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Antibody-mediated Rejection; Allosensitization

Keywords

Desensitization; antibody-mediated rejection; isatuximab

Outcome Measures

Primary Outcomes (6)

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

  Participants undergoing desensitization will have stable supplemental oxygen requirement or no supplemental oxygen requirement

  Day 0 (Visit 1)

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

  Participants undergoing desensitization will have stable supplemental oxygen requirement or no supplemental oxygen requirement

  Day 28 (Visit 5)

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

  Participants undergoing desensitization will have no presence of Donor-specific-antibody

  Day 0 (Visit 1)

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

  Participants undergoing desensitization will have no presence of Donor-specific-antibody

  Day 28 (Visit 5)

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

  Participants undergoing desensitization will have no presence of Donor-specific-antibody measured by DSA titer or by C1q assay.

  Day 0 (Visit 1)

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

  Participants undergoing desensitization will have no presence of Donor-specific-antibody measured by DSA titer or by C1q assay.

  Day 28 (Visit 5)

Secondary Outcomes (3)

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

  Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)

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

  Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)

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

  Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)

Study Arms (2)

Peri-transplant desensitization group

EXPERIMENTAL

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

Drug: Isatuximab; Procedure: bone marrow biopsy

Treatment of antibody-mediated rejection

EXPERIMENTAL

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.

Drug: Isatuximab

Interventions

Isatuximab DRUG

The dose will consist of isatuximab 10 mg/kg actual body weight given weekly for the first 4 weeks, followed by 10 mg/kg biweekly for an additional 4 doses. Isatuximab is a clear, colorless to slightly yellow solution. It is supplied as 100 mg/5 mL or 500 mg/25 mL single-dose vials.

Also known as: SARCLISA®

Peri-transplant desensitization group; Treatment of antibody-mediated rejection

bone marrow biopsy PROCEDURE

Bone marrow biopsy at the time of lung transplantation and at approximately 1 month following completion of therapy. Initial bone marrow biopsy to be performed during the lung transplant operation and to be collected from the sternum by the operating surgeon. Follow-up bone marrow biopsy to be completed by credentialed hematologist during a regularly scheduled follow-up bronchoscopy with standard procedural anesthesia sedation.

Peri-transplant desensitization group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Interventions

isatuximab

Study Officials

• Luis Angel, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: May 17, 2023
• Study Start: December 1, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to tyler.lewis@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)