Kidney TransplantationPhase 2NCT00722722
The Impact of Velcade(TM)on Antibody Secreting Cells in Sensitized Renal Allograft Candidates
A Phase 2 study testing Bortezomib in people with Kidney Transplantation, run by Mayo Clinic at 1 site in United States.
Trial summary
Patients planning to have kidney transplantation who are sensitized to their donors have high levels of donor specific alloantibodies. High levels of donor specific antibodies put kidney transplant recipients at risk for rejection very early after transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Apr 2014
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is post-menopausal, surgically sterilized, or she and/or sexual partner are willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
- Renal transplant candidates who otherwise meet our acceptance criteria.
- Evidence of alloantibody in their serum (panel reactive antibody >20% and specificities determined by single antigen flow bead assay).
- Sensitized patients with no living donors or have donor-specific antibody levels too high to undergo successful transplantation using our current protocols (T or B cell crossmatch channel shift >500).
Who cannot join
- Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.
- Patient has an absolute neutrophil count (ANC) of <1.0 x 10^9/L within 14 days before enrollment.
- Patient has >Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
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- Patient has received other investigational drugs within14 days before enrollment.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for malignancy within 5 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Contraindication to kidney transplantation-active infection, comorbid medical conditions, etc.
Trial locations and contacts
1 site in 1 country.
About this study
Patients planning to have kidney transplantation who are sensitized to their donors have high levels of donor specific alloantibodies. High levels of donor specific antibodies put kidney transplant recipients at risk for rejection very early after transplant. This study is trying to determine if the drug bortezomib (Velcade ™) can reduce donor specific alloantibodies to a level that permits kidney transplantation without a high risk for rejection.
Read the detailed description
The study is designed to assess the impact of in vivo treatment of bortezomib on anti-human leukocyte antigen (HLA) production by normal antibody secreting cells (ASC) in sensitized renal allograft candidates. The design involves treatment of subjects with bortezomib using one of three dosing regimens (4 doses, 16 doses or 32 doses of bortezomib). Using novel assays, anti-HLA production is determined by measuring the bone marrow derived ASC at baseline (prior to therapy) and after treatment (at day 14, 3 days after the last bortezomib dose). Paired data are used with patients serving as their own controls. Finally, the safety of bortezomib is evaluated by monitoring total serum antibody levels and the incidence of side effects (primarily neuropathy) at 1 month, the final follow-up point.
- Conditions
- Kidney Transplantation
- Being tested
- Bortezomib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade(TM)
Velcade given in four-dose cycles intravenously (through a vein).
| Study group | Role | What they receive |
|---|---|---|
| 4 dose group | Active comparator | 4 doses of bortezomib (1.3mg/m^2 of body surface area) Receives: Drug: Bortezomib |
| 16 dose group | Active comparator | 16 doses of bortezomib (1.3mg/m^2 of body surface area) Receives: Drug: Bortezomib |
| 32 dose group | Active comparator | 32 doses of bortezomib (1.3mg/m^2 of body surface area) Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to Bortezomib Monotherapy
Response to treatment with Bortezomib (BTZ) alone was defined as a reduction in serum Donor Specific Alloantibody (DSA) levels following treatment. DSA levels were measured prior to treatment and after treatment. A good response occurred if all DSA were reduced. A partial response when a reduction was observed in at least one DSA, but not all DSA. No response occurred when no reduction of any DSA was attained.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2008 (estimated)
- Study startJun 2008
- Primary completionApr 2014
- Study completionApr 2014
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Mark Stegall, Mayo Clinic
- Investigators
- Mark D. Stegall, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00722722
- Sponsor's protocol ID
- 08-000556
- Status last verified
- Apr 2016
- First submitted
- 23 Jul 2008
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Diwan TS, Raghavaiah S, Burns JM, Kremers WK, Gloor JM, Stegall MD. The impact of proteasome inhibition on alloantibody-producing plasma cells in vivo. Transplantation. 2011 Mar 15;91(5):536-41. doi: 10.1097/TP.0b013e3182081333.
PubMed 21283064Moreno Gonzales MA, Gandhi MJ, Schinstock CA, Moore NA, Smith BH, Braaten NY, Stegall MD. 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. Transplantation. 2017 Jun;101(6):1222-1227. doi: 10.1097/TP.0000000000001330.
PubMed 27379560
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Velcade(TM)on Antibody Secreting Cells in Sensitized Renal Allograft Candidates
- ClinicalTrials.gov ID
- NCT00722722
- Acronym / sponsor ID
- 08-000556
- Conditions
- Kidney Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Jun 2008
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 28 Jul 2008 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients planning to have kidney transplantation who are sensitized to their donors have high levels of donor specific alloantibodies. High levels of donor specific antibodies put kidney transplant recipients at risk for rejection very early after transplant. This study is trying to determine if the drug bortezomib (Velcade ™) can reduce donor specific alloantibodies to a level that permits kidney transplantation without a high risk for rejection.
Detailed description
The study is designed to assess the impact of in vivo treatment of bortezomib on anti-human leukocyte antigen (HLA) production by normal antibody secreting cells (ASC) in sensitized renal allograft candidates. The design involves treatment of subjects with bortezomib using one of three dosing regimens (4 doses, 16 doses or 32 doses of bortezomib). Using novel assays, anti-HLA production is determined by measuring the bone marrow derived ASC at baseline (prior to therapy) and after treatment (at day 14, 3 days after the last bortezomib dose). Paired data are used with patients serving as their own controls. Finally, the safety of bortezomib is evaluated by monitoring total serum antibody levels and the incidence of side effects (primarily neuropathy) at 1 month, the final follow-up point.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 4 dose group | Active comparator | Drug: Bortezomib4 doses of bortezomib (1.3mg/m^2 of body surface area) |
| 16 dose group | Active comparator | Drug: Bortezomib16 doses of bortezomib (1.3mg/m^2 of body surface area) |
| 32 dose group | Active comparator | Drug: Bortezomib32 doses of bortezomib (1.3mg/m^2 of body surface area) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Key exclusion criteria (10 listed)
- Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.
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 |
|---|---|---|
| BortezomibAlso: Velcade(TM)Velcade given in four-dose cycles intravenously (through a vein). | Drug | 16 dose group, 32 dose group, 4 dose group |
Primary outcome
Response to Bortezomib Monotherapy
Time frame: 6 months
Response to treatment with Bortezomib (BTZ) alone was defined as a reduction in serum Donor Specific Alloantibody (DSA) levels following treatment. DSA levels were measured prior to treatment and after treatment. A good response occurred if all DSA were reduced. A partial response when a reduction was observed in at least one DSA, but not all DSA. No response occurred when no reduction of any DSA was attained.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21283064Diwan TS, Raghavaiah S, Burns JM, Kremers WK, Gloor JM, Stegall MD. The impact of proteasome inhibition on alloantibody-producing plasma cells in vivo. Transplantation. 2011 Mar 15;91(5):536-41. doi: 10.1097/TP.0b013e3182081333.
- Derived from this study: PubMed 27379560Moreno Gonzales MA, Gandhi MJ, Schinstock CA, Moore NA, Smith BH, Braaten NY, Stegall MD. 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. Transplantation. 2017 Jun;101(6):1222-1227. doi: 10.1097/TP.0000000000001330.
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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.
Mark D. Stegall, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Kidney Transplantation, run by Mayo Clinic at 1 site 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 6 inclusion and 10 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 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 9 May 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?
Response to Bortezomib Monotherapy (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00722722, which also lists 2 linked publications.
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 9 May 2016.