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Primary Heart TransplantPhase 2NCT01769443

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

A Phase 2 study testing bortezomib and plasmapheresis in people with Primary Heart Transplant and Heart Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bortezomib and plasmapheresis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
14 sitesUnited States
Study dates
Jun 2013to Jul 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 15Show fewer
  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Cedars Sinai Heart Institute

    Beverly Hills, California, 90211

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • The Methodist Hospital

    Houston, Texas, 77030

  • Minneapolis Heart Institute

    Minneapolis, Minnesota, 55407

  • Intermountain Medical Center

    Murray, Utah, 84157

  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Drexel University College of Medicine

    Philadelphia, Pennsylvania, 19102

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of California at San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

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

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

Read the 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.

Being tested
bortezomib, plasmapheresis
Keywords
desensitization therapy, bortezomib (VELCADE®), plasmapheresis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bortezomibDrug

    Also called VELCADE®

    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.

  • plasmapheresisProcedure or surgery

    Also called apheresis (plasma)

    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.

Study groups in NCT01769443
Study groupRoleWhat they receive
No Desensitization TherapyNo interventionSubject(s) randomized to no desensitization therapy pre-transplant.
Desensitization TherapyExperimentalSubject(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.
Receives: Drug: bortezomib; Procedure: plasmapheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of Incidence of the Following Events in Subjects

    • 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.

    Measured: At transplant, or 90 days post-randomization, whichever occurs first

Secondary outcomes (18)

  1. Time From Wait Listing to Heart Transplantation

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  2. Change in Calculated PRA (cPRA) From Wait Listing to Transplantation

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  3. Incidence of Death

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  4. Incidence of Removal From Transplant Waiting List for Any Reason Except Improvement of Cardiac Function

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  5. Incidence of Initiation of Any Mechanical Circulatory Support Device

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  6. Incidence of Severe Infection Requiring Intravenous Antibiotics

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  7. Incidence of Cerebral Vascular Accident

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  8. Incidence of Acute Renal Failure Requiring Hemodialysis

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  9. Incidence of Administering Desensitization Therapy Beyond 90 Days After Randomization

    Measured: At transplant, or 1 year post-randomization, whichever occurs first

  10. Development of Angiographically Evident Cardiac Allograft Vasculopathy at 1 Year

    Measured: 24 and 52 weeks post-transplantation

  11. Incidence of Serious Infections Requiring Intravenous Antimicrobial Therapy

    Measured: 24 and 52 weeks post-transplantation

  12. Number of Subjects on Left Ventricular Assist Devices (LVAD) Compared to Those Not on LVADs

    Measured: 24 and 52 weeks post-transplantation

  13. Cardiac Dysfunction as Reflected in the Left Ventricular Ejection Fractions < 40% by Echocardiography, Angiogram or Nuclear Testing.

    Measured: 24 and 52 weeks:

  14. Incidence of Post-Transplant Lymphoproliferative Disorder (PTLD)

    Measured: 24 and 52 weeks post-transplantation

  15. Death

    Measured: 24 and 52 weeks post-transplantation

  16. Re-transplantation or Re-listed for Transplantation

    Measured: 24 and 52 weeks post-transplantation

  17. Incidence of Hospitalizations

    Measured: 24 and 52 weeks post-transplantation

  18. Incidence of Rejection Episodes Per Subject and Freedom From Rejection

    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).

    Measured: 24 and 52 weeks post-transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionJul 2014
  4. Study completionJul 2014

Why it stopped: Inability to enroll within funding period

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01769443
Sponsor's protocol ID
DAIT CTOT-13
Other IDs
U01AI063594
Status last verified
Sep 2026
First submitted
14 Jan 2013
Last updated
15 Oct 2026
Data monitoring committee
Yes

Publications

  • John R, Lietz K, Burke E, Ankersmit J, Mancini D, Suciu-Foca N, Edwards N, Rose E, Oz M, Itescu S. Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients. Circulation. 1999 Nov 9;100(19 Suppl):II229-35. doi: 10.1161/01.cir.100.suppl_2.ii-229.

    PubMed 10567309

  • Jordan SC, Vo A, Bunnapradist S, Toyoda M, Peng A, Puliyanda D, Kamil E, Tyan D. Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients. Transplantation. 2003 Aug 27;76(4):631-6. doi: 10.1097/01.TP.0000080685.31697.FC.

    PubMed 12973100

  • Leech SH, Lopez-Cepero M, LeFor WM, DiChiara L, Weston M, Furukawa S, Macha M, Singhal A, Wald JW, Nikolaidis LA, McClurken JB, Bove AA. Management of the sensitized cardiac recipient: the use of plasmapheresis and intravenous immunoglobulin. Clin Transplant. 2006 Jul-Aug;20(4):476-84. doi: 10.1111/j.1399-0012.2006.00509.x.

    PubMed 16842525

  • McGee EC Jr, Cotts W, Tambur AR, Friedewald J, Kim J, O'Connell J, Wallace S, McCarthy PM. Successful bridge to transplant in a highly sensitized patient with a complicated pump pocket infection. J Heart Lung Transplant. 2008 May;27(5):568-71. doi: 10.1016/j.healun.2008.02.006.

    PubMed 18442726

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bortezomib and plasmapheresis in people with Primary Heart Transplant and Heart Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of Incidence of the Following Events in Subjects (time frame: At transplant, or 90 days post-randomization, whichever occurs first). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01769443, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.

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