Clinical trial NCT00090194: Improving Transplant Options of Highly Sensitized Recipients Using IGIV-C, 10%
Official title: Evaluation of Immune Globulin Intravenous (Human), 10%, Manufactured by Chromatography Process (IGIV-C, 10%), as an Agent to Reduce Anti-HLA Antibodies and Improve Transplantation Results in Cross Match Positive Living Donor Kidney Allograft Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Failure, Chronic
Keywords: Kidney Transplantation
Transplantation, Homologous
HLA Antigens
Autoantibodies
Immunoglobulins, Intravenous
Living Donors
Dose-Response Relationship, Immunologic
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2004-08-26
Enrollment: 56
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria for Recipient:

* 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

Exclusion Criteria for Recipient:

* 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

Inclusion Criteria for Donor:

* 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

Primary outcomes:
measure: Monitoring of crossmatch conversion rate after one infusion of IGIV
Secondary outcomes:
measure: Graft survival and function
measure: average percentage panel reactive antibodies (PRA) reduction
measure: donor-specific unresponsiveness and allo-responsiveness in ESRD patients
measure: subject survival
measure: safety endpoints, including incidence rates of infection, adverse events, and hospitalizations
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan Regional Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of San Francisco
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Worcester
country: United States
facility: University of Massachusetts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
Study officials:
affiliation: Department of Pediatrics, Cedars-Sinai Medical Center
name: Stanley C. Jordan, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.