- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00908583
Desensitization in Kidney Transplantation
March 4, 2016 updated by: E. Steve Woodle, University of Cincinnati
Desensitization for Preformed Anti-HLA Antibodies in Kidney Transplantation
To determine if deletional strategies will provide effective desensitization.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed 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).
Study Type
Interventional
Enrollment (Actual)
44
Phase
- Phase 4
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
-
-
Ohio
-
Cincinnati, Ohio, United States, 45267
- University of Cincinnati
-
Cincinnati, Ohio, United States, 45267
- The Christ Hospital
-
-
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
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 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: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase 1, two stages
Patients will receive 1 dose of rituximab, 4 doses of bortezomib and plasmapheresis.
Rituximab will be given at a dose of 375 mg/m2 on day 32.
Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds.
Bortezomib will be administered on days 1, 4, 8, and 11.
For those patients who go on to Stage 2 of desensitization, bortezomib will be administered via IV push over 3-5 seconds during the pre-transplant period on days 32, 35, 39, 42.
Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization.
With the first and second doses, administer methylprednisolone 100mg via IV push.
With the third and fourth doses, administer methylprednisolone 50mg IVP.
|
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose.
Plasma volume replacement will be per physician discretion.
Patients will receive bortezomib as described in protocol
Other Names:
Patients will receive rituximab as described in protocol
Other Names:
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).
Other Names:
|
Experimental: Phase 2, two stages
Patients will receive 1 dose of rituximab, 4 doses of bortezomib and plasmapheresis.
Rituximab will be given at a dose of 375 mg/m2 on day -7.
Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds.
Bortezomib will be administered on days 1, 4, 8, and 11.
For those patients who go on to Stage 2 of desensitization, bortezomib will be administered via IV push over 3-5 seconds during the pre-transplant period on days 32, 35, 39, 42.
Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization.
With the first and second doses, administer methylprednisolone 100mg via IV push.
With the third and fourth doses, administer methylprednisolone 50mg IVP.
|
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose.
Plasma volume replacement will be per physician discretion.
Patients will receive bortezomib as described in protocol
Other Names:
Patients will receive rituximab as described in protocol
Other Names:
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).
Other Names:
|
Experimental: Phase 3, two stages
Patients will receive 1 dose of rituximab and 4 doses of bortezomib.
Rituximab will be given at a dose of 375 mg/m2 on day -7.
Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds.
Bortezomib will be administered on days 1, 4, 8, and 11.
For those patients who go on to Stage 2 of desensitization, bortezomib will be administered via IV push over 3-5 seconds during the pre-transplant period on days 23, 26, 30 and 33.
Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization.
With the first and second doses, administer methylprednisolone 100mg via IV push.
With the third and fourth doses, administer methylprednisolone 50mg IVP.
|
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose.
Plasma volume replacement will be per physician discretion.
Patients will receive bortezomib as described in protocol
Other Names:
Patients will receive rituximab as described in protocol
Other Names:
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).
Other Names:
|
Experimental: Phase 4, single stage
Patients will receive 1 dose of rituximab and 6 doses of bortezomib.
Rituximab will be given at a dose of 375 mg/m2 on day -7.
Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds.
Bortezomib will be administered during the pre-transplant period on days 1, 4, 8, and 11, 14, and 17.
Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization.
With the first and second doses, administer methylprednisolone 100mg via IV push.
With the third and fourth doses, administer methylprednisolone 50mg IVP.
|
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose.
Plasma volume replacement will be per physician discretion.
Patients will receive bortezomib as described in protocol
Other Names:
Patients will receive rituximab as described in protocol
Other Names:
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).
Other Names:
|
Experimental: Phase 5, single stage
Phase 5 evaluated even greater bortezomib dosing density by eliminating the inter-cycle dosing interval.
Phase 5 evaluated eight consecutive doses of bortezomib with one dose of rituximab.
Rituximab will be given at a dose of 375 mg/m2 on day -7.
Patient will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds.
Bortezomib will be administered on days 1, 4, 8, 11, 14, 17, 20, and 23.
Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization.
With the first and second doses, administer methylprednisolone 100mg via IV push.
With the third and fourth doses, administer methylprednisolone 50mg IVP.
|
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose.
Plasma volume replacement will be per physician discretion.
Patients will receive bortezomib as described in protocol
Other Names:
Patients will receive rituximab as described in protocol
Other Names:
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Living Donor Transplant Candidates That Are Transplanted
Time Frame: 1 year post baseline
|
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 post baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Safety of Bortezomib
Time Frame: Study Day 62
|
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
|
Number of Patients Whose Cytotoxic Panel Reactive Antibody (PRA) is Decreased by 50%
Time Frame: 46 days
|
Number of patients on the waiting list whose cytotoxic PRA is decreased by 50%.
|
46 days
|
Acute Rejection Rate
Time Frame: 6 months post transplant
|
Acute rejection rate at 6 months of all desensitized and transplanted patients
|
6 months post transplant
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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
May 1, 2009
Primary Completion (Actual)
November 1, 2012
Study Completion (Actual)
November 1, 2012
Study Registration Dates
First Submitted
May 26, 2009
First Submitted That Met QC Criteria
May 26, 2009
First Posted (Estimate)
May 27, 2009
Study Record Updates
Last Update Posted (Estimate)
April 1, 2016
Last Update Submitted That Met QC Criteria
March 4, 2016
Last Verified
March 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Antineoplastic Agents, Immunological
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
- Rituximab
- Bortezomib
Other Study ID Numbers
- X05295
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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