Clinical trial NCT05862766: Isatuximab in Lung Transplant Recipients
Official title: A Pilot Study of Isatuximab in Addition to Standard Therapy for Desensitization or Antibody-mediated Rejection in Lung Transplant Recipients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Antibody-mediated Rejection
Allosensitization
Keywords: Desensitization
antibody-mediated rejection
isatuximab
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2023-05-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)
timeFrame: Day 0 (Visit 1)
measure: Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)
timeFrame: Day 28 (Visit 5)
measure: Clinical Resolution, as measured by the number of participants with no presence of Donor-specific antibody (DSA)
timeFrame: Day 0 (Visit 1)
measure: Clinical Resolution, as measured by the number of participants with no presence of Donor-specific antibody (DSA)
timeFrame: Day 28 (Visit 5)
measure: Clinical Resolution, as measured by the number of participants with reduction of DSA titer
timeFrame: Day 0 (Visit 1)
measure: Clinical Resolution, as measured by the number of participants with reduction of DSA titer
timeFrame: Day 28 (Visit 5)
Secondary outcomes:
measure: Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with <2000 Mean fluorescent intensity (MFI) at 1:16 dilution
timeFrame: Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)
measure: Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with 2001-7999 Mean fluorescent intensity (MFI) at 1:16 dilution
timeFrame: Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)
measure: Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) ≥ 8000 Mean fluorescent intensity (MFI) at 1:16 dilution
timeFrame: Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Luis Angel, MD
role: PRINCIPAL_INVESTIGATOR
References: