Desensitization in Kidney Transplantation

HLA Sensitization Clinical Trial

Official title:

Desensitization for Preformed Anti-HLA Antibodies in Kidney Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00908583
• Other study ID #: X05295
• Status: Completed
• Phase: Phase 4
• First received: May 26, 2009
• Last updated: January 28, 2016
• Start date: May 2009
• Est. completion date: November 2012

Study information

• Verified date: January 2016
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To determine if deletional strategies will provide effective desensitization.

Description:

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLAantibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3mg/m2,6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n=20), Phase 2 (n=12), Phase 3 (n=10), Phase 4 (n=5), Phase 5 (n=5).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 65

• Voluntary written informed consent

• Patient on deceased donor wait list with a current or peak cytotoxic or calculated panel reactive antibody (PRA) > 20%

Exclusion Criteria:

• Myocardial infarction within 6 months

• Patient received investigational drug within 14 days prior to initiation of study treatment

• Serious medical or psychological illness

• Diagnosed with malignancy within three years, except complete research of basal cell carcinoma or squamous cell carcinoma of skin, an insitu malignancy or low risk prostate cancer after curative therapy

• Absolute neutrophil count (ANC) < 1000

• Receipt of live vaccine within 4 weeks of study entry

• Female subject that is breast feeding

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HLA Sensitization

Intervention

Drug:
• plasmapheresis
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose. Plasma volume replacement will be per physician discretion.
• Bortezomib
Patients will receive bortezomib as described in protocol
• Rituximab
Patients will receive rituximab as described in protocol
• Methylprednisolone
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).

Locations

Country	Name	City	State
United States	The Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Living Donor Transplant Candidates That Are Transplanted	Number of living donor transplant candidates who convert to a negative flow T- and B-cell crossmatch via desensitization and are subsequently transplanted	1 year	No
Secondary	Overall Safety of Bortezomib	Incidence of grade 3 and above non-hematologic toxicities. Incidence of grade 4 hematologic toxicities. Incidence of all grades of peripheral neuropathy. Incidence of Cytomegalovirus (CMV), Polyomavirus Allograft Nephropathy (PVN), and Posttransplant Lymphoproliferative Disorder (PTLD).	Study Day 62	Yes
Secondary	Number of Patients Whose Cytotoxic Panel Reactive Antibody (PRA) is Decreased by 50%	Number of patients on the waiting list whose cytotoxic PRA is decreased by 50%.	46 days	No
Secondary	Acute Rejection Rate	Acute rejection rate at 6 months of all desensitized and transplanted patients	6 months	No