Immunosuppression With Antithymocyte Globulin, Rituximab, Tacrolimus, Mycophenolate Mofetil and Sirolimus, Followed by Immunosuppression Withdrawal, in Living-donor Renal Transplant Recipients (ITN039ST)

Inclusion Criteria:

1. Recipient of a first renal allograft from a single haplotypematched or greater living
related donor. Also acceptable as a kidney donor is a second degree relative with an
HLA antigen type that is consistent with a single haplotype match with the recipient.

2. Demonstration of absence of anti-HLA antibodies using solid phase micro particle
technology (by Luminex® phenotype panel or Luminex single antigen bead test)
performed 7 days or less prior to the first dose of rituximab, as assessed by local
laboratories. A flow cytometry PRA may be performed in addition to the above, but is
not required. If performed, the flow cytometry PRA results should be documented
separately on the eCRF.

3. No evidence of anti-HLA antibodies in current or past sera. If an investigator feels
that a potential study participant, despite having evidence of anti-HLA antibodies in
past sera, should be considered for eligibility, then the investigator must request
that the candidate's data is reviewed by the adjudication committee.

4. Negative T and B cell flow crossmatches with the designated donor performed 7 days or
less prior to the first dose of rituximab, as assessed by local laboratories. If one
or more of the crossmatches is positive, the participant will be considered a screen
failure unless combined results of antibody and cross match testing implicate a
non-HLA antibody as the cause of the positive flow crossmatch. In this case, the
Protocol Chair must approve the participant as a screening success after consultation
with the local HLA Laboratory Director.

5. Single-organ recipients (kidney only).

6. Serologic evidence of prior exposure to Epstein-Barr virus (EBV).

7. For women of childbearing potential: a negative serum or urine pregnancy test with
sensitivity less than 50 mIU/m within 72 hours before the start of study medication.

8. Use of FDA-approved methods of contraception (those with less than a 5% failure rate)
or abstinence by all transplanted participants from the time that study treatment
begins until 104 weeks (24 months) after renal transplantation.

9. Ability to receive oral medication.

10. Ability to understand and provide informed consent. Kidney donors must meet all of
the following criteria to be eligible to participate in this study:

11. Age no greater than 65 years.

12. Ability to understand and provide informed consent.

Exclusion Criteria:

1. History of cancer within the last 5 years, except for nonmelanoma skin cell cancers
cured by local resection and cervical carcinoma in situ.

2. Women who are breastfeeding.

3. Uncontrolled hyperlipidemia (total serum cholesterol more than 300 mg/dL or
triglycerides more than 400 mg/dL).

4. Platelet count less than 100,000/μL at the screening visit.

5. Positive serology for HIV-1, hepatitis C virus, hepatitis B surface antigen, or
hepatitis B core antigen. Positive serologies for HCV or HBV must be confirmed by HCV
or HBV PCR respectively; as assessed by central laboratory assessments.

6. Active TB within 3 years of enrollment regardless of treatment history for TB.
Participants with a known positive purified protein derivative (PPD) or positive
QuantiFERON® (QFT) assay will not be eligible for the study unless they have
completed treatment for latent TB and have a negative chest x-ray. PPD or QFT testing
done within 52 weeks before transplant is acceptable as long as there is
documentation of the results. Prior recipients of a Bacille Calmette-Guérin (BCG)
vaccination are not exempt.

7. Underlying renal disease with a high risk of disease recurrence in the transplanted
kidney, including focal segmental glomerulosclerosis, type I or II
membranoproliferative glomerulonephritis and hemolytic-uremic syndrome/thrombotic
thrombocytopenic purpura.

8. The presence of any medical condition that the investigator deems incompatible with
participation in the trial.

9. Known sensitivity to ATG, rituximab, tacrolimus, MMF, sirolimus, or corticosteroids.

10. Current use of systemic corticosteroids or antibody-based therapies (e.g.,
infliximab, adalimumab, or etanercept).

11. Use of investigational drug, other than the study medications specified by the
protocol, within 30 days of transplantation.

12. Receipt of a live vaccine within 30 days of transplantation.