Safety and Efficacy of Desensitization Therapy in Sensitized Participants Awaiting Heart Transplantation
- Conditions
- Primary Heart TransplantHeart TransplantationHeart Transplant
- Interventions
- Procedure: plasmapheresis
- Registration Number
- NCT01769443
- Brief Summary
The primary objective is to evaluate the efficacy of desensitization therapy, which includes VELCADE® (bortezomib) and plasmapheresis, on select sensitized patients awaiting heart transplantation.
- Detailed Description
Bortezomib works by decreasing plasma cells in the blood. Plasma cells produce antibodies. Plasmapheresis is a procedure that removes antibodies from the blood. Plasma cells and antibodies produced by plasma cells can be involved in organ rejection after transplantation.
This trial will evaluate if decreasing plasma cells and antibodies with bortezomib and plasmapheresis can reduce complications while participants are waiting for their heart transplant. The evaluation of efficacy is defined by a lower complication rate while on the heart transplant waitlist.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
- Subject must be able to understand and provide informed consent;
- Candidate (as recipient) for a primary heart transplant (single organ transplant);
- Calculated panel reactive antibody (cPRA) of greater than 30% with a threshold using mean fluorescent intensity (MFI) of 3,000 or standard fluorescence intensity (SFI) of 60,000;
- Status 1 (1A or 1B) enrollment and randomization to occur within 2 weeks after status 1 listing;
- Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse;
- Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse;
- Negative test for HIV (human immunodeficiency virus), HBsAg (hepatitis B surface antigen), HBcAb (hepatitis B core antibody), and HCV (hepatitis C virus) antibodies within 6 months prior to study entry.
- Recipient of multiple solid organ or tissue transplants;
- Prior history of organ transplantation;
- Women of childbearing potential with a positive serum β-human chorionic gonadotropin (β-hCG) pregnancy test.Pregnancy testing is not required for postmenopausal or surgically sterilized women;
- Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow-up period;
- Subject has a hypersensitivity to VELCADE® (bortezomib), boron, or mannitol;
- Active systemic infection at time of enrollment;
- Any history of serologic positivity to HIV, HBsAg, HBcAb and HCV Ab;
- History of malignancy except when noted by an oncology specialist that tumor recurrence is low based on tumor type, response to therapy and negative metastatic work-up;
- Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy;
- Subjects with a platelet count of less than 75,000 within 7 days prior to enrollment;
- Subjects with an absolute neutrophil count (ANC) of less than 1,500 within 7 days prior to enrollment;
- Subjects with >1.5 x ULN (upper limit of normal) total bilirubin;
- Subjects with any grade or history of neuropathy;
- Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
- Participation in another interventional clinical trial or requiring treatment using un-marketed investigational drug(s) within 14 days of start of this trial and throughout the duration of this trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Desensitization Therapy plasmapheresis Subject(s) randomized to desensitization therapy pre-transplant. Desensitization therapy regimen pre-transplant: Plasmapheresis for 3 consecutive days (treatment days 0, 1 and 2) followed by concomitant bortezomib dosed at 1.3 mg/m\^2 as a 3 to 5 second bolus intravenous injection on treatment days 0, 3, 7 and 10. The first dose of bortezomib is administered between 4-8 hours after the first plasmapheresis session is completed and there must be at least 96 hours between the second and third dose of bortezomib. Desensitization Therapy bortezomib Subject(s) randomized to desensitization therapy pre-transplant. Desensitization therapy regimen pre-transplant: Plasmapheresis for 3 consecutive days (treatment days 0, 1 and 2) followed by concomitant bortezomib dosed at 1.3 mg/m\^2 as a 3 to 5 second bolus intravenous injection on treatment days 0, 3, 7 and 10. The first dose of bortezomib is administered between 4-8 hours after the first plasmapheresis session is completed and there must be at least 96 hours between the second and third dose of bortezomib.
- Primary Outcome Measures
Name Time Method Composite of Incidence of the Following Events in Subjects At transplant, or 90 days post-randomization, whichever occurs first * Death,
* Removal from the transplant waiting list for any reason except improvement of cardiac function,
* Initiation of any mechanical circulatory support device,
* Severe infection requiring intravenous antibiotics,
* Cerebral vascular accident,
* Acute renal failure requiring dialysis.
- Secondary Outcome Measures
Name Time Method Incidence of Hospitalizations 24 and 52 weeks post-transplantation Incidence of Post-Transplant Lymphoproliferative Disorder (PTLD) 24 and 52 weeks post-transplantation Death 24 and 52 weeks post-transplantation Re-transplantation or Re-listed for Transplantation 24 and 52 weeks post-transplantation Incidence of Rejection Episodes Per Subject and Freedom From Rejection 24 and 52 weeks post-transplantation Rejection is defined as follows:
* Biopsy proven acute rejection (BPAR) of any grade (cellular rejection per 2004 ISHLT \[International Society of Heart and Lung Transplantation\] grading scale),
* BPAR (individual grades),
* BPAR (Biopsy Proven Acute Rejection) \> 2R
* antibody mediated rejection (AMR),
* Any treated rejection,
* Rejection associated with hemodynamic compromise (HDC).Time From Wait Listing to Heart Transplantation At transplant, or 1 year post-randomization, whichever occurs first Change in Calculated PRA (cPRA) From Wait Listing to Transplantation At transplant, or 1 year post-randomization, whichever occurs first Incidence of Death At transplant, or 1 year post-randomization, whichever occurs first Incidence of Removal From Transplant Waiting List for Any Reason Except Improvement of Cardiac Function At transplant, or 1 year post-randomization, whichever occurs first Incidence of Initiation of Any Mechanical Circulatory Support Device At transplant, or 1 year post-randomization, whichever occurs first Incidence of Severe Infection Requiring Intravenous Antibiotics At transplant, or 1 year post-randomization, whichever occurs first Incidence of Cerebral Vascular Accident At transplant, or 1 year post-randomization, whichever occurs first Incidence of Acute Renal Failure Requiring Hemodialysis At transplant, or 1 year post-randomization, whichever occurs first Incidence of Administering Desensitization Therapy Beyond 90 Days After Randomization At transplant, or 1 year post-randomization, whichever occurs first Development of Angiographically Evident Cardiac Allograft Vasculopathy at 1 Year 24 and 52 weeks post-transplantation Incidence of Serious Infections Requiring Intravenous Antimicrobial Therapy 24 and 52 weeks post-transplantation Number of Subjects on Left Ventricular Assist Devices (LVAD) Compared to Those Not on LVADs 24 and 52 weeks post-transplantation Cardiac Dysfunction as Reflected in the Left Ventricular Ejection Fractions < 40% by Echocardiography, Angiogram or Nuclear Testing. 24 and 52 weeks:
Trial Locations
- Locations (14)
University of Utah
🇺🇸Salt Lake City, Utah, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Cedars Sinai Heart Institute
🇺🇸Beverly Hills, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Minneapolis Heart Institute
🇺🇸Minneapolis, Minnesota, United States