Rituximab and Intravenous Immunoglobulin (IVIG) for Desensitization in Renal Transplantation

March 24, 2008 updated by: Cedars-Sinai Medical Center

A Phase I/II Trial to Investigate the Safety and Efficacy of Rituximab and IVIG as Agents to Desensitize Highly-HLA Sensitized Dialysis Patients Awaiting Kidney Transplantation

The purpose of this study is to examine the safety and efficacy of IVIG in combination with Rituximab to lower the level of HLA-sensitive antibodies and block their ability to attack a transplanted organ in patients who are highly HLA-sensitized and are awaiting transplantation.

Study Overview

Status

Completed

Conditions

Kidney Transplant

Intervention / Treatment

Drug: IVIG and Rituximab

Detailed Description

Patients eligible for the study will be those who have anti-HLA antibody (Panel Reactive Antibody {PRA}) of >30%. If patients meet these criteria, patients will be asked to have an assessment of the ability of IVIG to reduce the anti-HLA antibodies activity in the test tube. Patients will receive IVIG 2gm/kg x1 on hemodialysis. Seven days later, patients will receive Rituximab 1gm in the CSMC Infusion Center as per protocol for Rituximab infusion. The second Rituximab infusion will be on day #22. Additional IVIG infusion will be given at month one.

Patients will continue to be followed for an additional 12 months after the last IVIG infusion and will be asked to return for follow up visits at month 1 through 5, month 7 and 12.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2
Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- California
  - Los Angeles, California, United States, 90048
    - 8700 Beverly Blvd.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients eligible for the study will be those who have anti-HLA antibody (Panel Reactive Antibody [PRA]) of >30% and are eligible for transplantation at Cedars-Sinai Medical Center. We currently anticipate entering 20 patients over the course of the study. We currently have ~100 patients on our wait list that would meet the above criteria. Patients will be selected based on the ability of IVIG to inhibit the cytotoxic anti-HLA antibody activity in vitro. They will then receive IVIG 2gm/kg X1 on day 1 while on hemodialysis. Seven days later, the patients will receive Rituxan® 1gm in the CSMC Cancer Infusion Center as per protocol for Rituxan® infusion. The second Rituxan® infusion will be on day#22. The patients will have monitoring of anti-HLA antibody and outlined tests as shown above.
Able and willing to give written informed consent and comply with the requirements of the study protocol
Adequate liver function, as indicated by normal liver function tests (NL: AST, ALT, Bilirubin and negative tests for hepatitis C and hepatitis B.
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.

Exclusion Criteria:

Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
- Receipt of a live vaccine within 4 weeks prior to randomization
- Previous Treatment with Rituximab (MabThera® / Rituxan®)
- Prior antibody therapy
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- History of HIV (positive HIV, HIV conducted during screening)
- History of Hepatitis B and/or Hepatitis C
- 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) or lactation
- 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)
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- Inability to comply with study and follow-up procedures

Laboratory Exclusion Criteria (at Screening)

Hemoglobin: < 8.5 gm/dL
Platelets: < 100,000/mm
AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
Positive Hepatitis B or C serology
Positive HIV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Success of transplantation Time Frame: 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number and severity of rejection episodes Time Frame: 12	12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cedars-Sinai Medical Center

Collaborators

Genentech, Inc.

Biogen

Investigators

Principal Investigator: Stanley C. Jordan, MD, Cedars-Sinai Medical Center
Study Director: Ashley A Vo, PharmD, Cedars-Sinai Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

May 1, 2007

Study Completion (Actual)