Antibody-mediated RejectionEarly Phase 1NCT05862766
Isatuximab in Lung Transplant Recipients
A Early Phase 1 study testing Isatuximab and bone marrow biopsy in people with Antibody-mediated Rejection and Allosensitization, run by NYU Langone Health at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Antibody-mediated Rejection, Allosensitization
- What is being tested?
- Isatuximab and bone marrow biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2024to 1 Jan 2027
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 13Show fewer
- 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)
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of Isatuximab in Addition to Standard Therapy for Desensitization or Antibody-mediated Rejection in Lung Transplant Recipients
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.
Read the 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.
- Conditions
- Antibody-mediated Rejection, Allosensitization
- Being tested
- Isatuximab, bone marrow biopsy
- Keywords
- Desensitization, antibody-mediated rejection, isatuximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsatuximabDrug
Also called SARCLISA®
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.
bone marrow biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Isatuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Percent Mean fluorescent intensity (MFI) change in undiluted serum
Measured: 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
Percent moderate titer DSA with <1000 Mean fluorescent intensity (MFI) at 1:16 dilution
Measured: 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
Percent Mean fluorescent intensity (MFI) reduction of high titer DSAs at 1:16 dilution
Measured: Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2023
- Study start1 Dec 2024 (estimated)
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jan 2027 (estimated)
Why it stopped: Study no longer had funding and therefore was closed before enrollment began.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antibody-mediated RejectionStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luis Angel, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05862766
- Sponsor's protocol ID
- 22-00992
- Status last verified
- Apr 2025
- First submitted
- 8 May 2023
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request and as agreed upon by the study team members.
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Isatuximab in Addition to Standard Therapy for Desensitization or Antibody-mediated Rejection in Lung Transplant Recipients
- ClinicalTrials.gov ID
- NCT05862766
- Acronym / sponsor ID
- 22-00992
- Conditions
- Antibody-mediated Rejection, Allosensitization
- Keywords
- Desensitization, antibody-mediated rejection, isatuximab
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study no longer had funding and therefore was closed before enrollment began.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 17 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Peri-transplant desensitization group | Experimental | Drug: Isatuximab, Procedure: bone marrow biopsyListed 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 of antibody-mediated rejection | Experimental | Drug: IsatuximabReceived 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsatuximabAlso: SARCLISA®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. | Drug | Peri-transplant desensitization group, Treatment of antibody-mediated rejection |
| bone marrow biopsyBone 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. | Procedure or surgery | Peri-transplant desensitization group |
Primary outcome
Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)
Time frame: Day 0 (Visit 1)
Participants undergoing desensitization will have stable supplemental oxygen requirement or no supplemental oxygen requirement
Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)
Time frame: Day 28 (Visit 5)
Participants undergoing desensitization will have stable supplemental oxygen requirement or no supplemental oxygen requirement
Clinical Resolution, as measured by the number of participants with no presence of Donor-specific antibody (DSA)
Time frame: Day 0 (Visit 1)
Participants undergoing desensitization will have no presence of Donor-specific-antibody
Clinical Resolution, as measured by the number of participants with no presence of Donor-specific antibody (DSA)
Time frame: Day 28 (Visit 5)
Participants undergoing desensitization will have no presence of Donor-specific-antibody
Clinical Resolution, as measured by the number of participants with reduction of DSA titer
Time frame: Day 0 (Visit 1)
Participants undergoing desensitization will have no presence of Donor-specific-antibody measured by DSA titer or by C1q assay.
Clinical Resolution, as measured by the number of participants with reduction of DSA titer
Time frame: Day 28 (Visit 5)
Participants undergoing desensitization will have no presence of Donor-specific-antibody measured by DSA titer or by C1q assay.
3 secondary outcomes
Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with <2000 Mean fluorescent intensity (MFI) at 1:16 dilution
Time frame: 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
Time frame: 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
Time frame: Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared upon reasonable request and as agreed upon by the study team members.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis Angel, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Isatuximab and bone marrow biopsy in people with Antibody-mediated Rejection and Allosensitization, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR) (time frame: Day 0 (Visit 1)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.