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

NCT ID: NCT01769443

Last Updated: 2015-11-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2014-07-31

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.

Conditions

Primary Heart Transplant; Heart Transplantation; Heart Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No Desensitization Therapy

Subject(s) randomized to no desensitization therapy pre-transplant.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

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.

plasmapheresis

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

VELCADE®; apheresis (plasma)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trials in Organ Transplantation

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jon A Kobashigawa, MD

Role: STUDY_CHAIR

Cedars-Sinai Heart Institute

Peter S. Heeger, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Cedars Sinai Heart Institute

Beverly Hills, California, United States

University of California at San Francisco

San Francisco, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

Mount Sinai School of Medicine

New York, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, 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

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 10567309 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12973100 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16842525 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18442726 (View on PubMed)

Related Links

http://www.niaid.nih.gov/Pages/default.aspx

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.ctotstudies.org/

Clinical Trials in Organ Transplantation (CTOT)

Other Identifiers

U01AI063594

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DAIT CTOT-13

Identifier Type: -

Identifier Source: org_study_id