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

This study has been completed.
Sponsor:
Collaborators:
Genentech
Biogen Idec
Information provided by:
Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT00642655
First received: March 19, 2008
Last updated: March 24, 2008
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Kidney Transplant
Drug: IVIG and Rituximab
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • Success of transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number and severity of rejection episodes [ Time Frame: 12 ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: September 2005
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00642655

Locations
United States, California
8700 Beverly Blvd.
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Genentech
Biogen Idec
Investigators
Principal Investigator: Stanley C. Jordan, MD Cedars-Sinai Medical Center
Study Director: Ashley A Vo, PharmD Cedars-Sinai Medical Center
  More Information

No publications provided by Cedars-Sinai Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stanley C. Jordan, MD, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT00642655     History of Changes
Other Study ID Numbers: U3176s
Study First Received: March 19, 2008
Last Updated: March 24, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Cedars-Sinai Medical Center:
IVIG
Rituximab
Highly Sensitized
Kidney Transplantation

Additional relevant MeSH terms:
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014