Desensitization in Kidney Transplantation

University of Cincinnati44 enrolled

Overview

To determine if deletional strategies will provide effective desensitization.

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HLA Sensitization

Interventions

plasmapheresisDRUG

Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose. Plasma volume replacement will be per physician discretion.

BortezomibDRUG

Patients will receive bortezomib as described in protocol

RituximabDRUG

Patients will receive rituximab as described in protocol

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (2)

The Christ Hospital

Cincinnati, Ohio, United States

University of Cincinnati

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

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

Time frame: 1 year post baseline

Secondary Outcomes

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).

Time frame: Study Day 62

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%.

Time frame: 46 days

Acute Rejection Rate

Acute rejection rate at 6 months of all desensitized and transplanted patients

Time frame: 6 months post transplant

Data from ClinicalTrials.gov

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