Disorder of Transplanted KidneyPhase 2NCT01349595
Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation
A Phase 2 study testing Bortezomib in people with Disorder of Transplanted Kidney, run by Mark Stegall at 1 site in United States.
Trial summary
The purpose of this study is to see if treating patients who have high levels of donor specific alloantibodies post-transplant with bortezomib might prevent the development of transplant glomerulopathy and preserve allograft function. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Disorder of Transplanted Kidney
- 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
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Mar 2015
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subject is either postmenopausal for at least 1 year before the screening visit, surgically sterilized, or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
- Male subjects, even if surgically sterilized (i.e. status postvasectomy), must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug or completely abstain from heterosexual intercourse.
- Kidney transplant recipients (living and deceased donors) who received a transplant in the last 3 years and have high Donor Specific Antibody (DSA) levels (defined as Mean Fluorescent Intensity levels >2000 by solid phase and single antigen bead LABscreen assays).
Who cannot join
- Patients who are recipients of ABO (blood type) incompatible kidney transplants.
- Patient with an Glomerular Filtration Rate (eGFR) ≤30 m/min at time of study entry.
- Patient with biopsy proven transplant glomerulopathy (Banff 2007 - cg score ≥2) within 2 months prior to randomization.
- Patients with biopsy-proven acute rejection at the time of randomization defined as Acute Cellular Rejection Patients with documented biopsy proven recurrence of disease or de novo glomerular disease post-transplant prior to enrollment.
- Patient has a platelet count of <30 x 10(9)/L within 14 days before enrollment.
- Patient has an absolute neutrophil count of <1.0 x 10(9)/L within 14 days before enrollment.
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- Patient has a history of post-transplant neutropenia on mycophenolate based immunosuppressive therapy.
- Evidence of severe liver disease with abnormal liver profile (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >3 times upper limit of normal [ULN]) at screening.
- Patient has >1.5 x ULN Total Bilirubin.
- Patient had any history of myocardial infarction in the past 3 years prior to enrollment or has New York Heart Association (NYHA) Class II to 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 ECG abnormality at screening must be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron, or mannitol.
- Female subject is pregnant or lactating.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Cytomegalovirus (CMV) sero-negative recipients who received a transplant from a CMV-sero-positive donor.(CMV- recipients of CMV- donor kidneys are acceptable)
- Epstein Barr Virus (EBV) sero-negative recipients.
- History of CMV + or EBV + viremia since transplantation.
- History of SPELL OUT HCV positivity (by PCR).
- History of Post-transplant lymphoproliferative disease.
- History of polyoma virus nephropathy or BK virus viremia (peripheral blood viral load of 5000 to 5,000,000 copies/mL).
- Patients who are HIV-positive or HBsAg-positive.
- Recipients of a kidney from a donor who tests positive for HIV, HBsAg or anti-HCV.
- Patients with current or recent severe systemic (pathogen detected in blood or Cerebrospinal fluid) infections within the 4 weeks prior to randomization.
- Diagnosed or treated for another malignancy within 3 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.
- Patient is currently receiving everolimus, sirolimus, or azathioprine as one of the immunosuppressive agents and intends to remain on this regimen.
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- Inability to perform followup or to undergo protocol biopsy.
- Active diabetic neuropathy at the time of treatment initiation.
- Patient has ≥Grade 2 peripheral neuropathy.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to see if treating patients who have high levels of donor specific alloantibodies post-transplant with bortezomib might prevent the development of transplant glomerulopathy and preserve allograft function.
- Conditions
- Disorder of Transplanted Kidney
- 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
Patients randomized to bortezomib treatment will receive 2, 4-dose cycles of drug followed by a 2 month "hiatus". At the end of this time, subjects will be re-evaluated for the appropriateness of receiving a 3rd and 4th cycle of bortezomib. Bortezomib will be given subcutaneously (under the skin). If unable to give subcutaneously, bortezomib will be given as a single IV (injection into vein) over a time of 3 to 5 seconds. Patients will receive up to 4, four-dose cycles of 1.3 mg/m(2) (based on body surface area).
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib | Experimental | Bortezomib is a type of targeted chemotherapy Receives: Drug: Bortezomib |
| Standard Post-transplant Treatment | No intervention | Mayo Clinic standard post kidney transplant follow-up. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Incidence of a Combined Endpoint of Death-censored Graft Loss or Greater Than 50% Reduction in Estimated Glomerular Filtration (eGFR) in Study Subjects.
Measured: 60 months after enrollment in the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2011 (estimated)
- Study startDec 2011
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: Study halted due to lack of funding
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 Disorder of Transplanted KidneyStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mark Stegall
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor-investigator, Mark Stegall, Mayo Clinic
- Investigators
- Mark Stegall, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01349595
- Sponsor's protocol ID
- 10-001487
- Status last verified
- Oct 2015
- First submitted
- 5 May 2011
- Last updated
- 28 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation
- ClinicalTrials.gov ID
- NCT01349595
- Acronym / sponsor ID
- 10-001487
- Conditions
- Disorder of Transplanted Kidney
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study halted due to lack of funding
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Mark StegallUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Dec 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 6 May 2011 (estimated)
- Results
- Posted 9 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if treating patients who have high levels of donor specific alloantibodies post-transplant with bortezomib might prevent the development of transplant glomerulopathy and preserve allograft function.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bortezomib | Experimental | Drug: BortezomibBortezomib is a type of targeted chemotherapy |
| Standard Post-transplant Treatment | No intervention | –Mayo Clinic standard post kidney transplant follow-up. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Female subject is either postmenopausal for at least 1 year before the screening visit, surgically sterilized, or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
- Male subjects, even if surgically sterilized (i.e. status postvasectomy), must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug or completely abstain from heterosexual intercourse.
- Kidney transplant recipients (living and deceased donors) who received a transplant in the last 3 years and have high Donor Specific Antibody (DSA) levels (defined as Mean Fluorescent Intensity levels >2000 by solid phase and single antigen bead LABscreen assays).
Key exclusion criteria (28 listed)
- Patients who are recipients of ABO (blood type) incompatible kidney transplants.
- Patient with an Glomerular Filtration Rate (eGFR) ≤30 m/min at time of study entry.
- Patient with biopsy proven transplant glomerulopathy (Banff 2007 - cg score ≥2) within 2 months prior to randomization.
- Patients with biopsy-proven acute rejection at the time of randomization defined as Acute Cellular Rejection Patients with documented biopsy proven recurrence of disease or de novo glomerular disease post-transplant prior to enrollment.
- 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: VelcadePatients randomized to bortezomib treatment will receive 2, 4-dose cycles of drug followed by a 2 month "hiatus". At the end of this time, subjects will be re-evaluated for the appropriateness of receiving a 3rd and 4th cycle of bortezomib. Bortezomib will be given subcutaneously (under the skin). If unable to give subcutaneously, bortezomib will be given as a single IV (injection into vein) over a time of 3 to 5 seconds. Patients will receive up to 4, four-dose cycles of 1.3 mg/m(2) (based on body surface area). | Drug | Bortezomib |
Primary outcome
The Incidence of a Combined Endpoint of Death-censored Graft Loss or Greater Than 50% Reduction in Estimated Glomerular Filtration (eGFR) in Study Subjects.
Time frame: 60 months after enrollment in the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
- 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.
Mark Stegall, MD 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 Disorder of Transplanted Kidney, run by Mark Stegall 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 3 inclusion and 28 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: stopped early, as of the sponsor's last update on 28 Oct 2015. 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 Sep 2015). 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?
The Incidence of a Combined Endpoint of Death-censored Graft Loss or Greater Than 50% Reduction in Estimated Glomerular Filtration (eGFR) in Study Subjects. (time frame: 60 months after enrollment in the study). 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 28 Oct 2015.