Effects of Rituximab and Mycophenolate Mofetil (MMF) on Highly Sensitized Patients Awaiting Renal Transplant

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by:
University of Washington
ClinicalTrials.gov Identifier:
NCT00446251
First received: March 9, 2007
Last updated: March 30, 2010
Last verified: March 2010
  Purpose

This is a 12-month phase 2, prospective, open label study to evaluate the effect of rituximab with mycophenolate mofetil (MMF)on the PRA of 14 highly sensitized patients who just completed an 8 month trial of MMF treatment alone. PRA values obtained at study enrollment and at 6 and 12 months on combined therapy as well as the rates of transplant will be compared and evaluated using descriptive analysis.


Condition Intervention Phase
Kidney Failure, Chronic
Diabetic Nephropathies
Glomerulonephritis, IGA
Hypertension, Renal
Drug: Rituximab
Drug: Mycophenolate mofetil (MMF)
Phase 2

University of Washington has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Highly Sensitized Patients: Effects of Rituximab and Mycophenolate Mofetil (MMF) On Anti-Human Leukocyte Antigen (HLA) Antibody Levels In Patients Awaiting Cadaveric Renal Transplant.

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • The Number of Subjects Who Experience a Decrease in Their Panel of Reactive Antibodies (PRA) at 6 Months Post Rituximab Infusion. [ Time Frame: Month 6 from start of study ] [ Designated as safety issue: No ]
    the number of subjects who experience a decrease in their Panel of Reactive Antibodies (PRA) at 6 months and 12 months post Rituximab infusion


Secondary Outcome Measures:
  • The Number of Subjects Who Experience a Change From Baseline in Their Panel of Reactive Antibody (PRA) Titers at 12 Months Post Rituximab Infusion. [ Time Frame: Month 12 from start of study ] [ Designated as safety issue: No ]
  • The Number of Subjects With a Negative Crossmatch at the Time of Transplant. [ Time Frame: Month 12 from start of study ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: December 2006
Study Completion Date: December 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Rituximab
    Rituximab dose is 1,000 mg given as an IV infusion every two weeks for 2 doses (days 1 and 15).
    Other Name: Rituxan, Rituximab
    Drug: Mycophenolate mofetil (MMF)
    Cellcept is continued from prior study, taken 500 - 1,000 mg BID, P.O.
    Other Name: mycophenolate mofetil, MMF, Cellcept
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age range 18 - 75, inclusive
  • Able and willing to give written informed consent and comply with the requirements of the study protocol
  • Outpatient status
  • Patients with a Panel of Reactive Antibodies (PRA) over 10% after an 8-month trial of MMF monotherapy
  • Patients with updated immunizations for tetanus, influenza, hepatitis B, pneumococcus
  • Patients with a negative purified protein derivative(PPD ) screen for tuberculosis (TB)within the last 6 months. If subject has a prior history of TB or positive PPD, documentation of adequate treatment is required.
  • Women who are of childbearing potential must have a negative serum pregnancy test prior to being enrolled in the study and agree to use a medically acceptable method of contraception throughout the study and for twelve months (1 year) after completion of treatment.
  • Men must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
  • Liver enzymes ALT and AST less than 2 times the normal limit.

Exclusion Criteria:

  • Active infection
  • Receipt of live vaccine within 4 weeks prior to first infusion.
  • Previous treatment with rituximab (MabThera® / Rituxan®)
  • History of multiple recurrent infections defined as more than 3 urinary tract infections, 2 episodes of pneumonia or 3 episodes of otitis/sinusitis in one year, or more than two dialysis line or peritoneal infections within one year.
  • Infection with hepatitis C virus (HCV) or hepatitis B virus(HBV) or human immunodeficiency virus (HIV), lack of documentation of treatment of a positive PPD, pregnant or breast-feeding, baseline leukopenia, white blood cell count (WBC) less than 4.0, thrombocytopenia (platelet count less than 100,000/mm) or difficult to treat anemia, a hematocrit chronically less than 32 on intravenous iron and EPO (erythropoietin) therapy, history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
  • Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • History of psychiatric disorder
  • Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00446251

Sponsors and Collaborators
University of Washington
Genentech
Investigators
Principal Investigator: Connie L Davis, MD University of Washington
  More Information

Publications:
Vieira CA, Agarwal A, Book BK, Sidner RA, Zeni T, Gebel HM, Roggero AL, Fineberg NA, Taber T, Kraus MA, Pescovitz MD. Rituxan for reduction of anti-HLA antibodies in patients awaiting renal transplantation. Am J Transplantation 2002;2:A870.

Responsible Party: Dr. Connie Davis, University of Washington
ClinicalTrials.gov Identifier: NCT00446251     History of Changes
Other Study ID Numbers: 25668-A, 04-0927-A 05
Study First Received: March 9, 2007
Results First Received: December 29, 2009
Last Updated: March 30, 2010
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Washington:
Dialysis
Kidney
Renal
Nephropathy
Glomerulonephropathy
Immunosuppression
Graft
Compatibility
Transplant
Diabetes
Hypertension
Transplantation, Kidney

Additional relevant MeSH terms:
Diabetic Nephropathies
Glomerulonephritis
Glomerulonephritis, IGA
Hypertension
Hypertension, Renal
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Nephritis
Autoimmune Diseases
Immune System Diseases
Vascular Diseases
Cardiovascular Diseases
Renal Insufficiency, Chronic
Mycophenolate mofetil
Rituximab
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014