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

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ClinicalTrials.gov Identifier: NCT00446251

Recruitment Status : Completed

First Posted : March 12, 2007

Results First Posted : March 29, 2010

Last Update Posted : April 6, 2010

Sponsor:

Collaborator:

Genentech, Inc.

Information provided by:

University of Washington

Study Description

Brief Summary:

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

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

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Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	14 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (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.
Study Start Date :	December 2006
Actual Primary Completion Date :	April 2008
Actual Study Completion Date :	December 2008

Resource links provided by the National Library of Medicine

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

Genetic and Rare Diseases Information Center resources: IgA Nephropathy Glomerulonephritis

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

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 ]
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 ]
The Number of Subjects With a Negative Crossmatch at the Time of Transplant. [ Time Frame: Month 12 from start of study ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00446251

Sponsors and Collaborators

University of Washington

Genentech, Inc.

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-López 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.

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, Bearden CM, Gebel HM, Roggero AL, Fineberg NS, Taber T, Kraus MA, Pescovitz MD. Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: 1. Safety, pharmacodynamics, and pharmacokinetics. Transplantation. 2004 Feb 27;77(4):542-8.


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 ( Other Identifier: University of Washington HSD study number )
First Posted:	March 12, 2007 Key Record Dates
Results First Posted:	March 29, 2010
Last Update Posted:	April 6, 2010
Last Verified:	March 2010

Keywords provided by University of Washington:


Dialysis Kidney Renal Nephropathy Glomerulonephropathy Immunosuppression	Graft Compatibility Transplant Diabetes Hypertension Transplantation, Kidney

Additional relevant MeSH terms:


Hypertension Kidney Diseases Renal Insufficiency Diabetic Nephropathies Kidney Failure, Chronic Glomerulonephritis Glomerulonephritis, IGA Hypertension, Renal Vascular Diseases Cardiovascular Diseases Urologic Diseases Diabetes Complications Diabetes Mellitus Endocrine System Diseases Renal Insufficiency, Chronic	Nephritis Autoimmune Diseases Immune System Diseases Rituximab Mycophenolic Acid Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antibiotics, Antineoplastic Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Enzyme Inhibitors

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