Multi-Drug Desensitization Protocol for Heart Transplant Candidates
|ClinicalTrials.gov Identifier: NCT01556347|
Recruitment Status : Terminated (Lack of efficacy)
First Posted : March 16, 2012
Results First Posted : June 15, 2018
Last Update Posted : June 15, 2018
Background: Patients may develop antibodies (human leukocyte antigen [HLA] alloantibodies) to other human tissues via pregnancy, transfusions or previous transplantation, which limits the ability to find an acceptable donor heart for transplantation. Such patients are at high risk for antibody mediated rejection, graft failure, and acute rejection (i.e. death). For successful transplantation, patients must receive organs from donors who lack the HLA antigens that correspond to their alloantibody specificities. No successful desensitization strategy currently exists.
Purpose: To determine if desensitization by deletion of immunologic memory with a multi-drug approach including anti-T and B cell therapies and anti-plasma cell therapy can effectively eliminate or significantly reduce alloantibody levels and permit highly sensitized patients to obtain a heart transplant. This therapy is anticipated to remove immunologic memory and will require re-immunization.
|Condition or disease||Intervention/treatment||Phase|
|Heart Transplantation||Drug: Bortezomib, Thymoglobulin, Rituximab, Gamimune N, (IVIG), Plasmapheresis||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multi-Drug Desensitization Protocol for Heart Transplant Candidates|
|Study Start Date :||July 2012|
|Actual Primary Completion Date :||May 2016|
|Actual Study Completion Date :||May 2016|
Experimental: Elimination of Immunologic Memory
A single arm multi-drug regimen is used to delete immunologic memory in order to reduce or eliminate alloreactive anti-HLA antibodies in highly sensitized heart transplant candidates. The intervention includes a protocol of Thymoglobulin, Rituximab, plasmapheresis and Bortezomib.
Drug: Bortezomib, Thymoglobulin, Rituximab, Gamimune N, (IVIG), Plasmapheresis
Other Name: Anti-thymocyte globulin (rabbit), Rituxan, Velcade
- Percentage of Patients With a Reduction in CPRA to Less Than 20% [ Time Frame: 365 days ]Percentage of highly sensitized heart transplant candidates, (patients with a CPRA greater than 50%), who have desensitization therapy, and then achieve a reduction in alloantibody such that their CPRA falls below 20%. For an individual patient, the outcome measure time frame is the one year of the Recovery Phase which begins after 218 days from the time that the patient begins the Induction Immunotherapy Phase, which is the same as the end of the Bortezomib Treatment Phase.
- Percentage of Patients Transplanted [ Time Frame: 365 days ]Percentage of patients, who are transplanted within one year of finishing the Bortezomib treatment phase.
- Percentage of Patients Who Suffer Mortality, a Serious Adverse Event, or Other Adverse Event During the Study Period [ Time Frame: 583 days ]Percentage of study patients who experience a serious safety issue during the three phases of the study as measured by all cause mortality, serious adverse reactions and other adverse reactions.
- Percentage of Patients Who Experience Grade 3 and Above Non-Hematologic Toxicities [ Time Frame: 583 days ]Percentage of patients who experience of grade 3 and above non-hematologic toxicities as measured by the incidence of hypersensitivity reaction, fever, nausea and vomiting or dehydration during the study period.
- The Percentage of Patients Who Experience Any Grade of Peripheral Neuropathy [ Time Frame: 583 days ]The percentage of patients in the study who experience any grade of peripheral neuropathy during the study period
- Percentage of Patients Who Experience CMV, PTLD, and PML [ Time Frame: 583 days ]Percentage of patients who experience cytomegalovirus (CMV), post-transplant lymphoproliferative disease (PTLD), or progressive multifocal leukoencephalopathy (PML) during the study period.
- The Percentage of Patients Who Experience Either a Respiratory Tract Infection or a Urinary Tract Infection [ Time Frame: 583 days ]The percentage of study patients who experience infectious complications in either the respiratory or urinary tracts during the study period.
- The Percentage of Patients Who Experience Exacerbations Cardiac Dysrhythmias or Heart Failure [ Time Frame: 583 days ]The percentage of study patients who experience an exacerbation of cardiac dysrhythmias and heart failure during the study period
- Percentage of Patients With Grade 4 Hematologic Toxicities [ Time Frame: 583 days ]A Grade 4 hematologic toxicity includes a platelet count < 25,000/mm3 or an absolute neutrophil count < 500/mm3
- The Percentage of Patients With Antibody Mediated Rejection After Transplantation [ Time Frame: 730 days ]The percentage of patients who experience antibody mediated rejection at 6 months and 1 year post transplant. The study period was 583 days, during which a patient was eligible for transplant during the last 365 days. If a patient was transplanted on day 583, then the patient is followed for one year after the transplant, then the total time to assess the two patients would have been a period of two years or 730 days. In fact, neither patient was transplanted within the study period.
- Percentage of Patients Who Develop De Novo Alloantibody or DSA Alloantibody After Transplant [ Time Frame: 730 days ]Percentage of patients who are transplanted with the study period who then develop de novo or donor-specific alloantibody (DSA) within one year post-transplant. The patients would be eligible for transplant after day 218 in the study protocol and the study had 365 days in which to be transplanted. If a patient was transplant on day 583,( the last day of eligibility), and then followed for one year, then the outcome time frame would be a total of two years. No patient was transplanted within the study period.
- Percentage of Patients Post-Transplant That Are DSA Negative [ Time Frame: 730 days ]Percentage of patients who receive a transplant within the study period who are then DSA negative at 1 year following transplantation.
- Percentage of Allograft Survival [ Time Frame: 730 days ]The percentage of allografts transplanted during the study period that survive to 6 and 12 months post transplant.
- The Percentage of Allografts That Endure Acute Rejection Within One Year of Transplantation [ Time Frame: 730 days ]The percentage of allografts that have an acute rejection episode per the criteria of the International Society of Heart and Lung Transplantation (ISHLT) within one year of transplantation. Allografts implanted during the Recovery Phase are monitored for a year for acute rejection per the study protocol. An allograft potentially implanted on the last day of a patient's recovery period would still be monitored for a year, so the potential outcome measure time would be 730 days. Since no allografts were implanted during the recovery period, there are no results to report.
- Percentage of Patients With a CPRA <20%, But Were Not Transplanted During the Study Period [ Time Frame: 583 days ]Proportion of patients who achieve a Calculated Panel Reactive Antibody test CPRA of < 20%, but are not transplanted within the study period.
- Percentage of Patients Who Receive Transplants Who Then Suffer Serious Post-transplant Complications [ Time Frame: 730 days ]Percentage of study patients who receive transplants within the study period who then experience death, allograft loss, hospitalization due to infection, and non-fatal serious adverse cardiac event (defined as acute myocardial infarction, congestive heart failure, need for percutaneous cardiac intervention, coronary artery bypass grafting, cardiac defibrillator placement, cerebral vascular accident, peripheral vascular disease) within 1 year of transplantation.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01556347
|United States, Washington|
|Providence Sacred Heart Medical Center|
|Spokane, Washington, United States, 99204|
|Principal Investigator:||Tiimothy B Icenogle, MD||Providence Sacred Heart Medical Center|