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

NCT00446251 | Completed Phase 2 Results DMC

• 2 other identifiers: 25668-A04-0927-A 05
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Kidney Failure, Chronic; Diabetic Nephropathies; Glomerulonephritis, IGA; Hypertension, Renal

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The Number of Subjects Who Experience a Decrease in Their Panel of Reactive Antibodies (PRA) at 6 Months Post Rituximab Infusion.

  the number of subjects who experience a decrease in their Panel of Reactive Antibodies (PRA) at 6 months and 12 months post Rituximab infusion

  Month 6 from start of study

Secondary Outcomes (2)

• The Number of Subjects Who Experience a Change From Baseline in Their Panel of Reactive Antibody (PRA) Titers at 12 Months Post Rituximab Infusion.

  Month 12 from start of study

• The Number of Subjects With a Negative Crossmatch at the Time of Transplant.

  Month 12 from start of study

Interventions

Rituximab DRUG

Rituximab dose is 1,000 mg given as an IV infusion every two weeks for 2 doses (days 1 and 15).

Also known as: Rituxan, Rituximab

Mycophenolate mofetil (MMF) DRUG

Cellcept is continued from prior study, taken 500 - 1,000 mg BID, P.O.

Also known as: mycophenolate mofetil, MMF, Cellcept

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Washington: lead
• Genentech, Inc.: collaborator

Related Publications (16)

• 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. doi: 10.1097/00007890-200203270-00013.

  PMID: 11923690 BACKGROUND

• 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. doi: 10.1097/00007890-199104000-00005.

  PMID: 2014527 BACKGROUND

• 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. doi: 10.1016/s0003-4975(02)03824-9.

  PMID: 12400781 BACKGROUND

• 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. doi: 10.1097/01.TP.0000058226.39732.32.

  PMID: 12698082 BACKGROUND

• 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. doi: 10.1097/00007890-200206270-00001.

  PMID: 12131677 BACKGROUND

• 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.

  PMID: 12736998 BACKGROUND

• 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. doi: 10.1002/ajh.10213.

  PMID: 12410580 BACKGROUND

• 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. doi: 10.1053/ajkd.2001.26092.

  PMID: 11479154 BACKGROUND

• 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. doi: 10.1200/JCO.1997.15.10.3266.

  PMID: 9336364 BACKGROUND

• 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. doi: 10.1016/s0041-1345(00)02395-2. No abstract available.

  PMID: 11267267 BACKGROUND

• 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. doi: 10.1159/000064293.

  PMID: 12119483 BACKGROUND

• 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.

  PMID: 7506951 BACKGROUND

• 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. doi: 10.1097/00007890-200011270-00023.

  PMID: 11118102 BACKGROUND

• 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. doi: 10.1034/j.1399-0012.2000.0140s3015.x.

  PMID: 11092347 BACKGROUND

• 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. doi: 10.1159/000046070.

  PMID: 11549905 BACKGROUND

• 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. doi: 10.1097/01.tp.0000112934.12622.2b.

  PMID: 15084932 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Diabetic Nephropathies; Glomerulonephritis, IGA; Hypertension, Renal; Kidney Diseases; Diabetes Mellitus; Hypertension

Interventions

Rituximab; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Complications; Endocrine System Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Connie L. Davis
• Organization: University of Washington

cdavis@u.washington.edu

206-598-6079

Study Officials

• Connie L Davis, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 9, 2007
• First Posted: March 12, 2007
• Study Start: December 1, 2006
• Primary Completion: April 1, 2008
• Study Completion: December 1, 2008
• Last Updated: April 6, 2010
• Results First Posted: March 29, 2010

Record last verified: 2010-03