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

Kidney Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00642655
• Other study ID #: U3176s
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 19, 2008
• Last updated: March 24, 2008
• Start date: September 2005
• Est. completion date: May 2007

Study information

• Verified date: March 2008
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Drug:
• IVIG and Rituximab
IVIG 2gm/kg given intravenously on day#0 and day#30 Rituximab 1gm given intravenously on day#7 and day#22

Locations

Country	Name	City	State
United States	8700 Beverly Blvd.	Los Angeles	California

Sponsors (3)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center	Biogen, Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success of transplantation		12 months	Yes
Secondary	Number and severity of rejection episodes		12	Yes