Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation
Study type: Interventional What is this?
Describes the nature of a clinical study. Types include:
- Observational study — observes people and measures outcomes without affecting results.
- Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
- Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
Study phase: II What is this?
During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.
- Rochester, Minnesota: 10-001487
NCT ID: NCT01349595
Sponsor Protocol Number: X05301
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.
Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.
See eligibility criteria
- 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 DSA levels (defined as MFI levels >2000 by solid phase and single antigen bead LABscreen assays).
- Patients who are recipients of ABO incompatible kidney transplants.
- Patient with an 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.
- 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.
- CMV sero-negative recipients who received a transplant from a CMV-sero-positive donor.(CMV- recipients of CMV- donor kidneys are acceptable)
- EBV sero-negative recipients.
- History of CMV + or EBV + viremia since transplantation.
- History of 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 CSF 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.
Participating Mayo Clinic locations
Study statuses change often. Please contact us for help.
|Mayo Clinic Location
Mayo Clinic principal investigator
Mark Stegall, M.D.
Closed for enrollment