Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow With Kidney Transplantation Patients

NCT00062712 | Completed Phase 2

• 2 other identifiers: 03020403-DK-0204
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with renal failure need chronic dialysis or a kidney transplant to survive. Most kidney transplant patients must take medicines indefinitely to prevent their immune systems from rejecting the kidney. Long-term exposure to these anti-rejection medicines can damage the transplanted kidney. The purpose of this study is to determine whether giving patients cells from the donor's bone marrow will reduce or eliminate the need for long-term use of these anti-rejection drugs. In addition to the donor's bone marrow cells, patients will receive the drugs thymoglobulin and sirolimus. A total of 20 patients will participate in this five-year study.

Conditions

Kidney Transplantation

Keywords

Immunosuppression; Transplant; Kidney Transplant

Interventions

Allogeneic Bone Marrow, Anti-Thymocyte Globulin (Sangstat) & Sirolimus (Wyeth-Ay DRUG

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Candidates for a kidney transplant.
• Age 12 through 60 at the time of transplant for the first 10 patients transplanted. Age 12 through 75 for subsequent patients. Patients younger than age 12 are better served being transplanted in a center with more extensive pediatric medical and nephrology support. Patients less than 12 years of age are also at higher risk for post transplant lymphoproliferative disorder following transplant than adults and intensive induction immunosuppression increases the risk further. The use of aggressive induction imunosuppression in this population would be inappropriate. Patients over the age of 75 generally require less immunosuppression than younger patients. The use of aggressive induction immunosuppression in this population would be inappropriate.
• Willingness to give informed consent.
• Availability of donor tissue for testing. This could include splenic or peripheral blood lymphocytes from a cadaveric donor or a willing living donor enrolled on the Clinical Center Living Donor Protocol who consents to periodic phlebotomy for peripheral blood lymphocyte isolation.
• Availability of adequate donor bone marrow for infusion.

You may not qualify if:

• Immunosuppressive drug therapy at the time of or 2 months prior to enrollment. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, antilymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive.
• Treatment with a nucleoside analogue chemotherapeutic agent (i.e. fludarabine phosphate, cladribine, or pentostatin) within 12 months of kidney transplant.
• Absolute lymphocyte count less than 1000/mm(3) prior to first dose of Thymogobulin.
• Any active malignancy or any history of a hematologic malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are appropriately treated prior to transplant.
• Donor/recipient combinations in which there are 0 HLA mismatches or in which the donor is homozygous for a shared HLA haplotype. Serologic HLA typing to be conducted at the Walter Reed Army Medical Center Tissue Typing Laboratory.
• Sensitization as defined by historical or current PRA less than 20 percent in patients receiving their first kidney allograft.
• First kidney graft survival less than 3 years as a consequence of acute/chronic rejection or positive T or B cell crossmatch in patients receiving second kidney allograft.
• Historical or current positive T cell cross match between donor and recipient.
• Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol allograft biopsies.
• Platelet count less than 75,000/mm(3) at the time of transplant.
• Any known immunodeficiency syndrome such as HIV, Chronic Granulomatous Disease, Severe Combined Immunodeficiency, DiGeorge Syndrome, etc.
• Presence of uncorrected cardiac insufficiency (either valvular or vascular) or major vascular disease.
• Subjects unwilling/unable to practice birth control if potentially fertile.
• Presence of active or chronic infection.
• Any condition that would likely increase the risk of protocol participation or confound data interpretation such as inability or unwillingness to comply with protocol monitoring and therapy, including, among others, a history of noncompliance, circumstances where compliance with protocol requirements is not feasible due to living conditions, travel restrictions, access to urgent medical services, or access to anti-rejection drugs after the research protocol is completed.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Wilson M, Burt AR, Milligan G, Anderson NG. Wortmannin-sensitive activation of p70s6k by endogenous and heterologously expressed Gi-coupled receptors. J Biol Chem. 1996 Apr 12;271(15):8537-40. doi: 10.1074/jbc.271.15.8537.

  PMID: 8621477 BACKGROUND

MeSH Terms

Interventions

Antilymphocyte Serum; Sirolimus

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 11, 2003
• First Posted: June 12, 2003
• Study Start: June 9, 2003
• Study Completion: March 22, 2007
• Last Updated: July 2, 2017

Record last verified: 2007-03-22

Locations

US (1)