Safety and Efficacy of Desensitization Therapy in Sensitized Participants Awaiting Heart Transplantation

This study has been terminated.
(Inability to enroll within funding period)
Sponsor:
Collaborator:
Clinical Trials in Organ Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01769443
First received: January 14, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

The purpose of this research study is to find out if the drug Bortezomib (VELCADE ®), along with a procedure called plasmapheresis, can be effective at desensitization.

Bortezomib works is by decreasing plasma cells in the blood. Plasma cells produce antibodies. Plasmapheresis is a procedure that removes antibodies from the blood. Plasma cells and the antibodies they produce can be involved in rejection after organ transplantation. This trial is trying to see if decreasing plasma cells and antibodies with Bortezomib and plasmapheresis can reduce complications while participants are waiting for their transplant and improve heart transplantation outcomes.


Condition Intervention Phase
Transplantation
Organ Transplantation
Heart Transplantation
Drug: Bortezomib
Procedure: Plasmapheresis on days 0, 1 and 2.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Multicenter, Two-parallel Arm Study Evaluating the Overall Efficacy and Safety of Desensitization Therapy on Selected Patients Awaiting Heart Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Composite of incidence of the following events in subjects [ Time Frame: at transplant, or 90 days postrandomization, whichever occurs first ] [ Designated as safety issue: No ]
    • 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:
  • Time from wait listing to transplantation. [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: No ]
  • Change in calculated PRA (cPRA) from wait listing to transplantation [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: No ]
  • Incidence of death. [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Incidence of removal from transplant waiting list for any reason except improvement of cardiac function [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Incidence of initiation of any mechanical circulatory support device [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Incidence of severe infection requiring intravenous antibiotics. [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Incidence of cerebral vascular accident [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Incidence of acute renal failure requiring hemodialysis [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Incidence of administering desensitization therapy beyond 90 days after randomization. [ Time Frame: at transplant, or 1 year post-randomization, whichever occurs first ] [ Designated as safety issue: Yes ]
  • Development of angiographically evident cardiac allograft vasculopathy at 1 year [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]
  • Incidence of serious infections requiring intravenous antimicrobial therapy [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]
  • Number of subjects on left ventricular assist devices (LVAD) compared to those not on LVADs. [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]
  • Cardiac dysfunction as reflected in the left ventricular ejection fractions < 40% by echocardiography, angiogram or nuclear testing. [ Time Frame: 24 and 52 weeks: ] [ Designated as safety issue: Yes ]
  • Incidence of Post-Transplant Lymphoproliferative Disorder (PTLD) [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]
  • Re-transplantation or re-listed for transplantation [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: No ]
  • Incidence of hospitalizations [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]
  • Incidence of rejection episodes per subject and freedom from rejection [ Time Frame: 24 and 52 weeks post-transplantation ] [ Designated as safety issue: Yes ]

    Rejection is defined as follows:

    • Biopsy proven acute rejection (BPAR) of any grade (cellular rejection per 2004 ISHLT grading scale),
    • BPAR (individual grades),
    • BPAR > 2R
    • antibody mediated rejection (AMR),
    • Any treated rejection,
    • Rejection associated with hemodynamic compromise (HDC).


Enrollment: 2
Study Start Date: July 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No Desentization Therapy Pre-transplantation.
Experimental: Desensitization Therapy
plasmapheresis for 3 consecutive days (treatment days 0, 1 and 2) followed by concomitant bortezomib dosed at 1.3 mg/m2 as a 3 to 5 second bolus intravenous inejection 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.
Drug: Bortezomib
Other Name: VELCADE®
Procedure: Plasmapheresis on days 0, 1 and 2.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must be able to understand and provide informed consent;
  • Candidate for a primary heart transplant recipient (single organ transplant);
  • cPRA of greater than 30% with a threshold using MFI of 3,000 or 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, HBsAg, HBcAb, and HCV Ab within 6 months prior to study entry.

Exclusion Criteria:

  • 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;
  • Patient 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;
  • Patients with a platelet count of less than 75,000 within 7 days prior to enrollment;
  • Patients with an absolute neutrophil count of less than 1,500 within 7 days prior to enrollment;
  • Patients with >1.5 x ULN Total Bilirubin;
  • Patients 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 an un-marketed investigational drugs within 14 days of start of this trial and throughout the duration of this trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769443

Locations
United States, California
Cedars Sinai Heart Institute
Beverly Hills, California, United States, 90211
University of California at San Francisco
San Francisco, California, United States, 94143
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States, 06510
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Minneapolis Heart Institute
Minneapolis, Minnesota, United States, 55407
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
United States, Texas
The Methodist Hospital
Houston, Texas, United States, 77030
United States, Utah
Intermountain Medical Center
Murray, Utah, United States, 84157
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Clinical Trials in Organ Transplantation
Investigators
Study Chair: Jon A Kobashigawa, MD Cedars-Sinai Heart Institute
Principal Investigator: Peter S. Heeger, MD Mount Sinai School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01769443     History of Changes
Other Study ID Numbers: DAIT CTOT-13, U01AI063594
Study First Received: January 14, 2013
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Desensitization, Immunologic
Plasmapheresis
bortezomib

Additional relevant MeSH terms:
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014