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

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:

MedlinePlus related topics: Diabetic Kidney Problems High Blood Pressure Kidney Failure Kidney Transplantation

Drug Information available for: Mycophenolic acid Mycophenolate sodium Mycophenolate mofetil hydrochloride Mycophenolate mofetil Rituximab

U.S. FDA Resources

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:

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

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:

Aranda JM Jr, Scornik JC, Normann SJ, Lottenberg R, Schofield RS, Pauly DF, Miles M, Hill JA, Sleasman JW, Skoda-Smith S. Anti-CD20 monoclonal antibody (rituximab) therapy for acute cardiac humoral rejection: a case report. Transplantation. 2002 Mar 27;73(6):907-10.

Dafoe DC, Bromberg JS, Grossman RA, Tomaszewski JE, Zmijewski CM, Perloff LJ, Naji A, Asplund MW, Alfrey EJ, Sack M, et al. Renal transplantation despite a positive antiglobulin crossmatch with and without prophylactic OKT3. Transplantation. 1991 Apr;51(4):762-8.

Garrett HE Jr, Groshart K, Duvall-Seaman D, Combs D, Suggs R. Treatment of humoral rejection with rituximab. Ann Thorac Surg. 2002 Oct;74(4):1240-2.

Gloor JM, Lager DJ, Moore SB, Pineda AA, Fidler ME, Larson TS, Grande JP, Schwab TR, Griffin MD, Prieto M, Nyberg SL, Velosa JA, Textor SC, Platt JL, Stegall MD. ABO-incompatible kidney transplantation using both A2 and non-A2 living donors. Transplantation. 2003 Apr 15;75(7):971-7.

Hack N, Angra S, Friedman E, McKnight T, Cardella CJ. Anti-idiotypic antibodies from highly sensitized patients stimulate B cells to produce anti-HLA antibodies. Transplantation. 2002 Jun 27;73(12):1853-8.

Holechek MJ, Hiller JM, Paredes M, Rickard JC, Montgomery RA. Expanding the living organ donor pool: positive crossmatch and ABO incompatible renal transplantation. Nephrol Nurs J. 2003 Apr;30(2):195-204.

Jillella AP, Dainer PM, Kallab AM, Ustun C. Treatment of a patient with end-stage renal disease with Rituximab: pharmacokinetic evaluation suggests Rituximab is not eliminated by hemodialysis. Am J Hematol. 2002 Nov;71(3):219-22.

Libetta C, Rampino T, Dal Canton A. Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients. Am J Kidney Dis. 2001 Aug;38(2):286-95.

Maloney DG, Grillo-Lopez AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997 Oct;15(10):3266-74.

Miura S, Okazaki H, Satoh T, Amada N, Ohashi Y. Long-term follow-up of living donor renal transplant recipients sensitized after donor specific blood transfusion. Transplant Proc. 2001 Feb-Mar;33(1-2):1221-3. No abstract available.

Nitta K, Akiba T, Kawashima A, Kimata N, Miwa N, Nishida E, Uchida K, Honda K, Yumura W, Nihei H. Characterization of TH1/TH2 profile in uremic patients. Nephron. 2002 Jul;91(3):492-5.

Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435-45.

Schweitzer EJ, Wilson JS, Fernandez-Vina M, Fox M, Gutierrez M, Wiland A, Hunter J, Farney A, Philosophe B, Colonna J, Jarrell BE, Bartlett ST. A high panel-reactive antibody rescue protocol for cross-match-positive live donor kidney transplants. Transplantation. 2000 Nov 27;70(10):1531-6.

Takeda A, Uchida K, Haba T, Tominaga Y, Katayama A, Kobayashi T, Oikawa T, Morozumi K. Acute humoral rejection of kidney allografts in patients with a positive flow cytometry crossmatch (FCXM). Clin Transplant. 2000;14 Suppl 3:15-20.

Yokoyama T, Nitta K, Futatsuyama K, Hayashi T, Honda K, Uchida K, Kawashima A, Yumura W, Nihei H. Identification of T helper cell subsets in continuous ambulatory peritoneal dialysis patients. Nephron. 2001 Oct;89(2):215-8.

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 May 19, 2013