The Effect of Rituximab on the Development of Anti-Donor Antibodies

NCT00695097 | Completed Results

• 1 other identifier: GNE Rituxin
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of the study is to find out if Rituximab, which is an antibody against specific white cells involved in rejection, when combined with standard anti-rejection treatment can more effectively reverse the rejection process. Our hypothesis is that with acute rejection there is activation of B cells and the subsequent development of anti-donor antibodies that ultimately lead to graft loss. More effective therapy targeted at B cells may abort the development of anti-HLA antibodies, prevent renal injury and have a favorable effect on long-term graft outcome.

Conditions

Renal Transplant Rejection

Keywords

Rituximab; Renal Transplant Rejection; B cells; Patients with biopsy proven acute rejection cellular infiltrate, B cells

Outcome Measures

Primary Outcomes (1)

• Change in Biopsy Cell Densities From Baseline to Follow-up

  Follow-up biopsy was done 3-6 months after study treatment. Study follow-up monthly for 1 year.

  1 year

Study Arms (2)

1

ACTIVE COMPARATOR

Rituximab Group: The Rituximab dose is 1000mg (1gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15) and followed up monthly for 1 year. Biopsy was done Baseline and Month 3 and other labs (CBC/Diff, Platelets, HACA, PK, Serum Creatinine, 24-hour protein, HLA antibodies, flow cytometry, and serology testing). Physical exam and vital signs were done.

Drug: Rituximab

2

ACTIVE COMPARATOR

No Rituximab: received standard immunosuppression and was followed up monthly for 1 year. Labs (CBC/Diff, Platelets, HACA, PK, Serum Creatinine, 24-hour protein, HLA antibodies, flow cytometry, and serology testing) vital signs, and physical exam was done.

Drug: No Rituximab

Interventions

Rituximab DRUG

Rituximab infusion on Day 1 and Day 15

Also known as: Rituxan

1

No Rituximab DRUG

No Rituximab

2

Eligibility Criteria

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

You may qualify if:

• Recipients of a kidney transplant or kidney-pancreas transplant with predominant findings on kidney biopsy of acute rejection and the presence of as B cells by immunohistochemistry
• Patients between 18 and 65 years of age
• Patients known not to be allergic to Rituximab
• Able and willing to give written informed consent and comply with the requirements of the study protocol
• Adequate renal function as indicated by serum creatinine less than 6 mg/dL
• negative serum pregnancy test (for women of child bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
• Patients who have received a kidney-pancreas transplant.
• Patients who on immunohistochemistry have evidence of B cell infiltration

You may not qualify if:

• Patients who have undergoing multi-organ transplant except for kidney-pancreas patients.
• Patients who have been administered an experimental drug in the 3 months preceding enrollment in the study
• Receipt of a live vaccine within 4 weeks prior to randomization
• Previous Treatment with Rituximab (MabThera® / Rituxan®)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of HIV (positive HIV, HIV conducted during screening if applicable)
• History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)
• History of recurrent significant infection or history of recurrent bacterial infections
• Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• Lack of peripheral venous access
• History of drug, alcohol, or chemical abuse within 6 months prior to screening
• Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment)
• 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 insitu of the cervix.
• History of psychiatric disorder being treated with medications
• Hemoglobin: \< 7 gm/dL

Sponsors & Collaborators

• University of California, San Francisco: lead
• Genentech, Inc.: collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

UCSF-Kidney Transplant Clinic

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The limitations were small number of participants and short follow up time of only 12 months.

Results Point of Contact

• Title: Flavio Vincenti
• Organization: University of California, San Francisco

flavio.vincenti@ucsfmedctr.org

415-353-1322

Study Officials

• Flavio Vincenti, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2008
• First Posted: June 11, 2008
• Study Start: August 1, 2004
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: March 26, 2014
• Results First Posted: March 26, 2014

Record last verified: 2014-02

Locations

US (2)