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

October 14, 2015 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Prospective, Randomized, Multicenter, Two-Parallel Arm Study Evaluating the Overall Efficacy and Safety of Desensitization Therapy on Selected Patients Awaiting Heart Transplantation

The primary objective is to evaluate the efficacy of desensitization therapy, which includes VELCADE® (bortezomib) and plasmapheresis, on select sensitized patients awaiting heart transplantation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Beverly Hills, California, United States, 90211
        • Cedars Sinai Heart Institute
      • San Francisco, California, United States, 94143
        • University of California at San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Minneapolis Heart Institute
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital
    • Utah
      • Murray, Utah, United States, 84157
        • Intermountain Medical Center
      • Salt Lake City, Utah, United States, 84132
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

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;
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: No Desensitization Therapy
Subject(s) randomized to no desensitization therapy pre-transplant.
Experimental: Desensitization Therapy

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.
Drug: bortezomib
Bortezomib dosed at 1.3 mg/m^2 as a 3 to 5 second bolus administered by 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.
Other Names:
  • VELCADE®
Procedure: plasmapheresis
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 administered by 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.
Other Names:
  • apheresis (plasma)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite of Incidence of the Following Events in Subjects
Time Frame: 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.
At transplant, or 90 days post-randomization, whichever occurs first

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time From Wait Listing to Heart Transplantation
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Change in Calculated PRA (cPRA) From Wait Listing to Transplantation
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Incidence of Death
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
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
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Incidence of Initiation of Any Mechanical Circulatory Support Device
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Incidence of Severe Infection Requiring Intravenous Antibiotics
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Incidence of Cerebral Vascular Accident
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Incidence of Acute Renal Failure Requiring Hemodialysis
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Incidence of Administering Desensitization Therapy Beyond 90 Days After Randomization
Time Frame: At transplant, or 1 year post-randomization, whichever occurs first
At transplant, or 1 year post-randomization, whichever occurs first
Development of Angiographically Evident Cardiac Allograft Vasculopathy at 1 Year
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Incidence of Serious Infections Requiring Intravenous Antimicrobial Therapy
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Number of Subjects on Left Ventricular Assist Devices (LVAD) Compared to Those Not on LVADs
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Cardiac Dysfunction as Reflected in the Left Ventricular Ejection Fractions < 40% by Echocardiography, Angiogram or Nuclear Testing.
Time Frame: 24 and 52 weeks:
24 and 52 weeks:
Incidence of Post-Transplant Lymphoproliferative Disorder (PTLD)
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Death
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Re-transplantation or Re-listed for Transplantation
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Incidence of Hospitalizations
Time Frame: 24 and 52 weeks post-transplantation
24 and 52 weeks post-transplantation
Incidence of Rejection Episodes Per Subject and Freedom From Rejection
Time Frame: 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).
24 and 52 weeks post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Clinical Trials in Organ Transplantation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jon A Kobashigawa, MD, Cedars-Sinai Heart Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 14, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 11, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DAIT CTOT-13
  • U01AI063594 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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