Improving Transplant Options of Highly Sensitized Recipients Using IGIV-C, 10%

NCT ID: NCT00090194

Last Updated: 2017-01-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2004-03-31

Brief Summary

The purpose of this study is to determine if IGIV-C, 10% will be effective in converting a donor-recipient crossmatch status from positive to negative. The crossmatch test is used to determine if the donor tissue and recipient tissue are compatible. The study will also evaluate if IGIV-C, 10% will allow successful kidney transplantation in a patient who otherwise would not be able to receive a transplant. Three dose levels of IGIV-C, 10% will be evaluated to determine what dose level is most effective.

Detailed Description

Kidney transplantation has emerged as the treatment of choice for patients with end-stage renal disease (ESRD). Preliminary data suggest that IGIV therapy could have significant benefits in modifying allograft rejection episodes, stabilizing long-term allograft function, and reducing ischemia/reperfusion injury.

Qualified patients will have an in-vitro assessment of the ability of IGIV-C, 10% to convert the donor-specific crossmatch (cytotoxic assay) from positive to negative. Those patients with successful in-vitro conversion of the donor-specific crossmatch assay will be randomized to receive IGIV-C, 10% intravenously at a dose of either 2 gm/kg, 1 gm/kg, or 0.5 gm/kg. IGIV-C, 10% will be administered 3 to 5 days prior to planned transplantation and, if transplantation is successful, 7 days post-transplant. If after receiving the IGIV-C infusion the donor-specific crossmatch reveals that cell death has fallen to 20% or less above background, the crossmatch will be considered negative. If after receiving one infusion the crossmatch remains positive, additional IGIV-C infusions may be administered at one-month intervals, up to 4 infusions. A repeat crossmatch must be obtained after each infusion. Patients will be followed for 12 months post-transplant. Concomitant therapy will include a standard immunosuppression regimen of mycophenolate mofetil, tacrolimus, and prednisone following induction therapy with thymoglobulin.

Conditions

Kidney Failure, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose

0.5 gm/kg at 5 days pre-transplant and 7 days post-transplant

Group Type: EXPERIMENTAL

Immune Globulin Intravenous (Human), 10%

Intervention Type: BIOLOGICAL

Middle Dose

1.0 gm/kg at 5 days pre-transplant and 7 days post-transplant

Group Type: EXPERIMENTAL

Immune Globulin Intravenous (Human), 10%

Intervention Type: BIOLOGICAL

High Dose

2.0 gm/kg at 5 days pre-transplant and 7 days post-transplant

Group Type: EXPERIMENTAL

Immune Globulin Intravenous (Human), 10%

Intervention Type: BIOLOGICAL

Interventions

Immune Globulin Intravenous (Human), 10%

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• End-stage renal disease
• No known contraindications for therapy with IGIV-C, 10%
• Have identified a living kidney donor
• Positive crossmatch with the intended donor
• Parent or guardian willing to provide consent, if applicable

• Positive donor-specific crossmatch with the intended recipient
• ECOG performance status 0 or 1
• Excellent health
• Acceptable laboratory parameters
• Compatible blood type
• Normal heart and lung evaluations
• Parent or guardian willing to provide consent, if applicable

Exclusion Criteria

• Pregnant or breastfeeding
• Women of child-bearing age who are not willing or able to practice approved methods of contraception
• HIV infection
• Hepatitis B or hepatitis C infection
• History of positive tuberculin skin test
• Selective IgA deficiency, known anti-IgA antibodies, or history of severe allergy to any part of the clinical trial material
• Have received or will receive multiple organ transplants
• Any licensed or investigational live attenuated vaccine within 2 months of the screening visit
• Patients deemed unable to comply with the protocol
• Heart attack within 1 year of screening
• History of clinically significant thrombotic episodes or active peripheral vascular disease
• Investigational agents within 4 weeks of study entry

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stanley C. Jordan, MD

Role: STUDY_CHAIR

Department of Pediatrics, Cedars-Sinai Medical Center

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Banner Good Samaritan Regional Medical Center

Phoenix, Arizona, United States

UCLA Medical Center

Los Angeles, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of San Francisco

San Francisco, California, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

University of Miami

Miami, Florida, United States

Emory University Hospital

Atlanta, Georgia, United States

Indiana University Medical Center

Indianapolis, Indiana, United States

University of Massachusetts Medical Center

Worcester, Massachusetts, United States

University of Michigan Hospitals

Ann Arbor, Michigan, United States

University of Cincinnati

Cincinnati, Ohio, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Medical Branch

Galveston, Texas, United States

Swedish Medical Center

Seattle, Washington, United States

Countries

United States

References

Akalin E, Ames S, Sehgal V, Fotino M, Daly L, Murphy B, Bromberg JS. Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell crossmatch-positive patients. Transplantation. 2003 Nov 27;76(10):1444-7. doi: 10.1097/01.TP.0000084200.40159.EC.

Reference Type: BACKGROUND

PMID: 14657683 (View on PubMed)

Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant. 2003 Jun;3(6):653-64. doi: 10.1034/j.1600-6143.2003.00121.x.

Reference Type: BACKGROUND

PMID: 12780556 (View on PubMed)

Jordan SC, Vo A, Bunnapradist S, Toyoda M, Peng A, Puliyanda D, Kamil E, Tyan D. Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients. Transplantation. 2003 Aug 27;76(4):631-6. doi: 10.1097/01.TP.0000080685.31697.FC.

Reference Type: BACKGROUND

PMID: 12973100 (View on PubMed)

Jordan SC, Vo AA, Toyoda M, Tyan D, Nast CC. Post-transplant therapy with high-dose intravenous gammaglobulin: Applications to treatment of antibody-mediated rejection. Pediatr Transplant. 2005 Apr;9(2):155-61. doi: 10.1111/j.1399-3046.2005.00256.x.

Reference Type: BACKGROUND

PMID: 15787786 (View on PubMed)

Zachary AA, Montgomery RA, Ratner LE, Samaniego-Picota M, Haas M, Kopchaliiska D, Leffell MS. Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients. Transplantation. 2003 Nov 27;76(10):1519-25. doi: 10.1097/01.TP.0000090868.88895.E0.

Reference Type: BACKGROUND

PMID: 14657698 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

DAIT IG03

Identifier Type: -

Identifier Source: org_study_id