A Phase 2 interventional study of Belatacept and Carfilzomib in Lung Transplant Rejection and Antibody-mediated Rejection, sponsored by Duke University. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-05-02.
Sponsored by Duke University · Phase 2, Interventional, and Treatment
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.
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.
Duke University is the lead sponsor of 2,025 studies on the registry; 275 are open to participants now.
Of its 194 completed or terminated interventional studies of FDA-regulated products, 159 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Inclusion criteria for the AMR post-transplant cohort
Inclusion criteria for the pre-transplant desensitization cohort
Exclusion criteria for both AMR post-transplant cohort and pre-transplant cohort
Treatment with Belatacept and Carfilzomib for subjects who show evidence of antibody-mediated rejection (AMR) following lung transplantation.
Drug: Belatacept · Drug: Carfilzomib
Treatment with Belatacept and Carfilzomib for subjects with elevated human leukocyte antigen (HLA) antibodies prior to lung transplantation.
Drug: Belatacept · Drug: Carfilzomib
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.
Also known as: Nulojix
20mg/m2 Plasmapheresis
Also known as: Kyprolis
Occurrence of drug side effects
Drug tolerability with respect to freedom from drug side effects measured using descriptive statistics
Time frame: Within 28 days of last administration of study drugs
Occurrence of infection
Drug tolerability with respect to freedom from infection measured using descriptive statistics
Time frame: Within 28 days of last administration of study drugs
Occurrence of malignancy
Drug tolerability with respect to freedom from malignancy measured using descriptive statistics
Time frame: Within 28 days of last administration of study drugs
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.
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
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.
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
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.
Time frame: 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.
Time frame: 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.
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
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.
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
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.
Time frame: Within 4 weeks of completion of treatment
No study locations are listed for this record.
Plan to share: No
No publications or documents are linked to this record.
This study is withdrawn, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Duke University