HLA SensitizationPhase 4NCT00908583
Desensitization in Kidney Transplantation
A Phase 4 study testing plasmapheresis, Bortezomib and Rituximab in people with HLA Sensitization, run by University of Cincinnati at 2 sites in United States.
Trial summary
To determine if deletional strategies will provide effective desensitization. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HLA Sensitization
- What is being tested?
- plasmapheresis, Bortezomib and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2009to Nov 2012
- Phase
- Phase 4
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Christ Hospital
Cincinnati, Ohio, 45267
University of Cincinnati
Cincinnati, Ohio, 45267
About this study
Official title: Desensitization for Preformed Anti-HLA Antibodies in Kidney Transplantation
To determine if deletional strategies will provide effective desensitization.
Read the 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).
- Conditions
- HLA Sensitization
- Being tested
- plasmapheresis, Bortezomib, Rituximab, Methylprednisolone
- Keywords
- Alloantibody, Desensitization, Kidney Transplantation, Nephrology, Plasma Cells, Translational Research/Science
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
plasmapheresisDrug
Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose. Plasma volume replacement will be per physician discretion.
BortezomibDrug
Also called Velcade
Patients will receive bortezomib as described in protocol
RituximabDrug
Also called Rituxan
Patients will receive rituximab as described in protocol
Also called Medrol
Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).
| Study group | Role | What they receive |
|---|---|---|
| Phase 1, two stages | Experimental | 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. Receives: Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone |
| Phase 2, two stages | Experimental | 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. Receives: Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone |
| Phase 3, two stages | Experimental | 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. Receives: Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone |
| Phase 4, single stage | Experimental | 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. Receives: Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone |
| Phase 5, single stage | Experimental | 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. Receives: Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year post baseline
Secondary outcomes (3)
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).
Measured: 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%.
Measured: 46 days
Acute Rejection Rate
Acute rejection rate at 6 months of all desensitized and transplanted patients
Measured: 6 months post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2009 (estimated)
- Study startMay 2009
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HLA SensitizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, E. Steve Woodle, University of Cincinnati
- Investigators
- E. Steve Woodle, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00908583
- Sponsor's protocol ID
- X05295
- Status last verified
- Mar 2016
- First submitted
- 26 May 2009
- Last updated
- 1 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Desensitization for Preformed Anti-HLA Antibodies in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT00908583
- Acronym / sponsor ID
- X05295
- Conditions
- HLA Sensitization
- Keywords
- Alloantibody, Desensitization, Kidney Transplantation, Nephrology, Plasma Cells, Translational Research/Science
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- May 2009
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 27 May 2009 (estimated)
- Results
- Posted 26 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine if deletional strategies will provide effective desensitization.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 1, two stages | Experimental | Drug: plasmapheresis, Drug: Bortezomib, Drug: Rituximab, Drug: MethylprednisolonePatients 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. |
| Phase 2, two stages | Experimental | Drug: plasmapheresis, Drug: Bortezomib, Drug: Rituximab, Drug: MethylprednisolonePatients 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. |
| Phase 3, two stages | Experimental | Drug: plasmapheresis, Drug: Bortezomib, Drug: Rituximab, Drug: MethylprednisolonePatients 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. |
| Phase 4, single stage | Experimental | Drug: plasmapheresis, Drug: Bortezomib, Drug: Rituximab, Drug: MethylprednisolonePatients 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. |
| Phase 5, single stage | Experimental | Drug: plasmapheresis, Drug: Bortezomib, Drug: Rituximab, Drug: MethylprednisolonePhase 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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%
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| plasmapheresisPatients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose. Plasma volume replacement will be per physician discretion. | Drug | Phase 1, two stages, Phase 2, two stages, Phase 3, two stages, Phase 4, single stage, Phase 5, single stage |
| BortezomibAlso: VelcadePatients will receive bortezomib as described in protocol | Drug | Phase 1, two stages, Phase 2, two stages, Phase 3, two stages, Phase 4, single stage, Phase 5, single stage |
| RituximabAlso: RituxanPatients will receive rituximab as described in protocol | Drug | Phase 1, two stages, Phase 2, two stages, Phase 3, two stages, Phase 4, single stage, Phase 5, single stage |
| MethylprednisoloneAlso: MedrolEach bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses). | Drug | Phase 1, two stages, Phase 2, two stages, Phase 3, two stages, Phase 4, single stage, Phase 5, single stage |
Primary outcome
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
3 secondary outcomes
Overall Safety of Bortezomib
Time frame: Study Day 62
Number of Patients Whose Cytotoxic Panel Reactive Antibody (PRA) is Decreased by 50%
Time frame: 46 days
Acute Rejection Rate
Time frame: 6 months post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
E. Steve Woodle, MD principal investigator
University of Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing plasmapheresis, Bortezomib and Rituximab in people with HLA Sensitization, run by University of Cincinnati at 2 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 3 inclusion and 7 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: finished, as of the sponsor's last update on 1 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 26 Feb 2016). 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?
Number of Living Donor Transplant Candidates That Are Transplanted (time frame: 1 year post baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Apr 2016.