Rituximab in Kidney Transplantation

Trial Summary

The purpose of this study is to determine whether treatment with rituximab in people who develop new anti-HLA antibodies after kidney transplant will promote longer-term survival of the transplanted kidney.

Eligibility

• Participant willing to provide informed consent
• Previously diagnosed end stage renal disease (ESRD)
• Received kidney transplant within 3 and 36 months of study entry
• Willing to comply with the study protocol
• Willing to use acceptable forms of contraception during the study and for 12 months
  following rituximab/placebo therapy
• Willing to refrain from breastfeeding during the study and for 12 months following
  rituximab/placebo therapy

• Parent or guardian willing to provide informed consent
• Have received all childhood vaccinations prior to study entry

• Three to 39 months post-transplant
• Developed new antibodies detected at two time points within 1 month between 3 to 36
  months post-transplant
• Negative pregnancy test

• Recipient of a kidney from a donor older than 70 years of age
• Multi-organ transplant
• History of organ transplantation other than current kidney transplantation
• Previous treatment with rituximab
• History of severe allergic reactions to monoclonal antibodies
• History of allergic reaction to iodine glomerular filtration rate (GFR) assay
• Lack of IV venous access
• Sensitized to greater than 5% Panel Reactive Antibody (PRA) within 12 weeks prior to
  transplant
• History of recurrent bacterial or other significant infections
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including
  tuberculosis [TB] or atypical mycobacterial disease) or any major episode of
  infection requiring hospitalization or treatment with intravenous antibiotics within
  4 weeks of study entry. Patients with fungal infections of nail beds are not
  excluded.
• HIV infected
• Surface antigen positive for hepatitis B virus (HBV)
• Antibody positive for hepatitis C virus (HCV)
• History of drug, alcohol, or chemical abuse within 6 months prior to study entry
• History of cancer. Patients with adequately treated in situ cervical carcinoma or
  adequately treated basal or squamous cell carcinoma of the skin are not excluded.
• Clinically significant cardiovascular or pulmonary disease
• Evidence of urinary tract obstruction causing decreased kidney function, unless
  corrected by study entry
• Any other disease, metabolic dysfunction, physical examination finding, or clinical
  laboratory finding that would contraindicate use of an investigational drug, may
  affect interpretation of study results, or put the patient at high risk for treatment
  complications
• History of psychiatric disorder that may interfere with participation in the study
• History of nonadherence to prescribed regimens
• Use of other investigational drugs within 4 weeks of study entry
• Received any licensed or investigational live attenuated vaccine within 2 months of
  study entry

• Previous treatment with rituximab
• History of severe allergic reactions to monoclonal antibodies
• History of cancer. Patients with adequately treated in situ cervical carcinoma or
  adequately treated basal or squamous cell carcinoma of the skin are not excluded.
• Active systemic infection at the time of entry into Stage 2
• Recurrent or de novo glomerular disease or Banff Grade III chronic rejection other
  than chronic humoral rejection (CHR) indicated in baseline kidney biopsy
  post-transplant
• History of post-transplant lymphoproliferative disease (PTLD)
• Serum creatinine of 3.0 mg/dl or greater OR GFR less than 25 ml/min at the time of
  entry into Stage 2
• Hemoglobin less than 8.5 g/dl
• Platelets less than 80,000 cells/mm3
• White blood cell count less than 3,000 cells/mm3
• AST or ALT 2.5 times the upper limit of normal at study entry
• Pregnant or breast-feeding
• Absolute neutrophil count less than 1000/mm3

Detailed Description

• Group 1 adult participants, 18 years of age or older, will receive an intravenous
  infusion of 1000mg of rituximab at Days 0 and 14. Group 1 pediatric participants, 18
  years of age or younger, will receive an intravenous infusion of 375 mg/m2 of rituximab
  at Days 0, 8, 15 and 22.
• Group 2 adult participants, 18 years of age or older, will receive an intravenous
  infusion of 1000mg of placebo at Days 0 and 14. Group 2 pediatric participants, 18
  years of age or younger, will receive an intravenous infusion of 375 mg/m2 of placebo
  at Days 0, 8, 15, and 22.

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

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