Lung Transplant RejectionPhase 2NCT03805178
Lung Transplant Plasmapheresis/Belatacept/Carfilzomib for Antibody Mediated Rejection and Desensitization
A Phase 2 study testing Belatacept and Carfilzomib in people with Lung Transplant Rejection and Antibody-mediated Rejection, run by Duke University.
Trial summary
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. This proposal would include belatacept in a multi-therapy regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Transplant Rejection, Antibody-mediated Rejection
- What is being tested?
- Belatacept and Carfilzomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2019to 30 Oct 2020
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Positive DSAs and allograft dysfunction defined by changes in pulmonary physiology, gas exchange, radiological features or deteriorating functional performance that is highly suspicious for AMR
- Recipient is Epstein-Barr virus positive (EBV+) by serology
- Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure
- Inclusion criteria for the pre-transplant desensitization cohort
- Elevated HLA antibodies (defined as MFI >1000) such that the calculated panel reactive antibodies are >60%
- At least 2 HLA antibodies with Mean Fluorescent Intensity (MFI) <10,000 and at least 2 HLA antibodies with MFI <5,000 on undiluted serum that do not demonstrate an increase in MFI with dilution at 1:16 (no evidence of a prozone effect).
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- EBV+ by serology
- Clinically stable defined by not on invasive mechanical ventilation, extracorporeal membrane oxygenation support or other invasive life support requiring ICU level of care
- Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure
- Exclusion criteria for both AMR post-transplant cohort and pre-transplant cohort
- Active systemic infection
- Allergy to carfilzomib or belatacept
- Known malignancy in the previous 2 years except for non-melanomatous skin cancer
- Pregnancy
- Inability to commit to complete treatment protocol at Duke as all procedures must be completed at Duke
- Prisoners or those who are compulsory detained
Who cannot join
None listed.
About this study
Official title: Lung Transplant Plasmapheresis (PLEX)/Belatacept/Carfilzomib Protocol for Treatment of Antibody Mediated Rejection (AMR) and Desensitization
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. This proposal would include belatacept in a multi-therapy regimen. Open label study with two patient cohorts for safety and efficacy of belatacept in a multi-modal protocol. The two patient cohorts are an AMR post-transplant cohort and pre-transplant desensitization cohort. A total of 10 patients will be enrolled.The primary objection is drug tolerability and secondary objectives are antibody measurements and allograft function.
Read the detailed description
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. Multimodal therapies with rituximab, intravenous immunoglobulin, plasmapheresis and proteasome inhibitors have not significantly altered the antibodies in these patients. Belatacept targets the T and B cell interaction such that it represents a novel therapeutic strategy. This proposal would include belatacept in a multi-therapy regimen.
This is an open label study with two patient cohorts for safety and efficacy of belatacept in a multi-modal protocol. The two patient cohorts are an AMR post-transplant cohort and pre-transplant desensitization cohort. A total of 10 patients will be enrolled.The primary objection is drug tolerability and secondary objectives are antibody measurements and allograft function.
- Being tested
- Belatacept, Carfilzomib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelataceptDrug
Also called Nulojix
Initial phase: 10 mg/kg on days 0 and 4, and again at weeks 2 and 4. Maintenance phase: 10 mg/kg every month beginning 4 weeks after completion of the initial phase.
No dosage adjustments required for renal or hepatic impairment. No known drug interactions for usual post-transplant medication regimen.
CarfilzomibDrug
Also called Kyprolis
20mg/m2 Plasmapheresis
| Study group | Role | What they receive |
|---|---|---|
| Rejection post-transplant | Experimental | Treatment with Belatacept and Carfilzomib for subjects who show evidence of antibody-mediated rejection (AMR) following lung transplantation. Receives: Drug: Belatacept; Drug: Carfilzomib |
| Pre-transplant desensitization | Experimental | Treatment with Belatacept and Carfilzomib for subjects with elevated human leukocyte antigen (HLA) antibodies prior to lung transplantation. Receives: Drug: Belatacept; Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of drug side effects
Drug tolerability with respect to freedom from drug side effects measured using descriptive statistics
Measured: Within 28 days of last administration of study drugs
Occurrence of infection
Drug tolerability with respect to freedom from infection measured using descriptive statistics
Measured: Within 28 days of last administration of study drugs
Occurrence of malignancy
Drug tolerability with respect to freedom from malignancy measured using descriptive statistics
Measured: Within 28 days of last administration of study drugs
Secondary outcomes (7)
Number of subjects in the AMR cohort with resolution of at least one donor specific human leukocyte antigen (HLA) antibody (DSA)
Descriptive statistical report of number of subjects who had resolution of at least one DSA measured by absolute Mean Fluorescent Intensity (MFI) change and log change using pre and post treatment values for each antibody.
Measured: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with improvement or stabilization of lung function as measured by spirometry data
Pulmonary function (spirometry) data will track forced vital capacity (FVC), forced expiratory volume (FEV1) and forced expiratory flow (FEF) 25-75%. Changes in spirometry will be reported as stabilized, improved or worsened based on comparison of baseline spirometry values obtained prior to treatment plan with serial spirometric testing performed at specified intervals in treatment plan.
Measured: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with improvement in oxygenation as measured by Liters/min oxygen at rest
Gas exchange will be reported as no change, worsening exchange or improving exchange based on comparison of resting oxygen requirements before and following treatment plan.
Measured: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with decrease in DSA by one log
Descriptive statistical report of number of subjects who had a decrease in DSA measured by absolute Mean Fluorescent Intensity (MFI) change and log change using pre and post treatment values for each antibody.
Measured: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with elimination of DSA at 1:16 dilution
Descriptive statistical report of number of subjects who had elimination of DSA at 1:16 dilution measured by absolute Mean Fluorescent Intensity (MFI) change and log change using pre and post treatment values for each antibody.
Measured: Within 4 weeks of completion of treatment
Number of subjects in the transplant desensitization cohort with decrease in non-DSA HLA antibodies by one log
Descriptive statistical report of number of subjects who had a decrease in non-DSA HLA antibodies measured by absolute Mean Fluorescent Intensity (MFI) change and log change using pre and post treatment values for each antibody.
Measured: Within 4 weeks of completion of treatment
Number of subjects in the transplant desensitization cohort with elimination of non-DSA HLA antibodies at 1:16 dilution
Descriptive statistical report of number of subjects who had elimination of non-DSA HLA antibodies at 1:16 dilution measured by absolute Mean Fluorescent Intensity (MFI) change and log change using pre and post treatment values for each antibody.
Measured: Within 4 weeks of completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2019
- Study start1 May 2019 (estimated)
- Primary completion1 Aug 2020 (estimated)
- Study completion30 Oct 2020 (estimated)
Why it stopped: Not activated at Duke
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Laurie Snyder, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03805178
- Sponsor's protocol ID
- Pro00101289
- Other IDs
- IM103-407
- Status last verified
- Apr 2019
- First submitted
- 14 Jan 2019
- Last updated
- 2 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung Transplant Plasmapheresis (PLEX)/Belatacept/Carfilzomib Protocol for Treatment of Antibody Mediated Rejection (AMR) and Desensitization
- ClinicalTrials.gov ID
- NCT03805178
- Acronym / sponsor ID
- Pro00101289
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not activated at Duke
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 1 May 2019 (estimated)
- Primary completion
- 1 Aug 2020 (estimated)
- Study completion
- 30 Oct 2020 (estimated)
- First posted
- 15 Jan 2019 (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.
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. This proposal would include belatacept in a multi-therapy regimen. Open label study with two patient cohorts for safety and efficacy of belatacept in a multi-modal protocol. The two patient cohorts are an AMR post-transplant cohort and pre-transplant desensitization cohort. A total of 10 patients will be enrolled.The primary objection is drug tolerability and secondary objectives are antibody measurements and allograft function.
Detailed description
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. Multimodal therapies with rituximab, intravenous immunoglobulin, plasmapheresis and proteasome inhibitors have not significantly altered the antibodies in these patients. Belatacept targets the T and B cell interaction such that it represents a novel therapeutic strategy. This proposal would include belatacept in a multi-therapy regimen.
This is an open label study with two patient cohorts for safety and efficacy of belatacept in a multi-modal protocol. The two patient cohorts are an AMR post-transplant cohort and pre-transplant desensitization cohort. A total of 10 patients will be enrolled.The primary objection is drug tolerability and secondary objectives are antibody measurements and allograft function.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rejection post-transplant | Experimental | Drug: Belatacept, Drug: CarfilzomibTreatment with Belatacept and Carfilzomib for subjects who show evidence of antibody-mediated rejection (AMR) following lung transplantation. |
| Pre-transplant desensitization | Experimental | Drug: Belatacept, Drug: CarfilzomibTreatment with Belatacept and Carfilzomib for subjects with elevated human leukocyte antigen (HLA) antibodies prior to lung transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Positive DSAs and allograft dysfunction defined by changes in pulmonary physiology, gas exchange, radiological features or deteriorating functional performance that is highly suspicious for AMR
- Recipient is Epstein-Barr virus positive (EBV+) by serology
- Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure
- Inclusion criteria for the pre-transplant desensitization cohort
- Elevated HLA antibodies (defined as MFI >1000) such that the calculated panel reactive antibodies are >60%
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| BelataceptAlso: NulojixInitial phase: 10 mg/kg on days 0 and 4, and again at weeks 2 and 4. Maintenance phase: 10 mg/kg every month beginning 4 weeks after completion of the initial phase. No dosage adjustments required for renal or hepatic impairment. No known drug interactions for usual post-transplant medication regimen. | Drug | Pre-transplant desensitization, Rejection post-transplant |
| CarfilzomibAlso: Kyprolis20mg/m2 Plasmapheresis | Drug | Pre-transplant desensitization, Rejection post-transplant |
Primary outcome
Occurrence of drug side effects
Time frame: Within 28 days of last administration of study drugs
Drug tolerability with respect to freedom from drug side effects measured using descriptive statistics
Occurrence of infection
Time frame: Within 28 days of last administration of study drugs
Drug tolerability with respect to freedom from infection measured using descriptive statistics
Occurrence of malignancy
Time frame: Within 28 days of last administration of study drugs
Drug tolerability with respect to freedom from malignancy measured using descriptive statistics
7 secondary outcomes
Number of subjects in the AMR cohort with resolution of at least one donor specific human leukocyte antigen (HLA) antibody (DSA)
Time frame: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with improvement or stabilization of lung function as measured by spirometry data
Time frame: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with improvement in oxygenation as measured by Liters/min oxygen at rest
Time frame: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with decrease in DSA by one log
Time frame: Within 4 weeks of completion of treatment
Number of subjects in the AMR cohort with elimination of DSA at 1:16 dilution
Time frame: Within 4 weeks of completion of treatment
Number of subjects in the transplant desensitization cohort with decrease in non-DSA HLA antibodies by one log
Time frame: Within 4 weeks of completion of treatment
Number of subjects in the transplant desensitization cohort with elimination of non-DSA HLA antibodies at 1:16 dilution
Time frame: Within 4 weeks of completion of treatment
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 2 May 2019.
- Individual participant dataSharing planned: No
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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.
Laurie Snyder principal investigator
Duke University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belatacept and Carfilzomib in people with Lung Transplant Rejection and Antibody-mediated Rejection, run by Duke University.
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 16 inclusion and 0 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 2 May 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Occurrence of drug side effects (time frame: Within 28 days of last administration of study drugs). The study lists 3 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 2 May 2019.