Belatacept Post Depletional Repopulation to Facilitate Tolerance
Condition: Organ Transplantation
Intervention: Belatacept; Sirolimus; Alemtuzumab
Intervention description: Belatacept will be given within 24 hours of transplantation via a peripheral intravenous catheter at a dose of 10mg/kg (actual body weight) infused over 30 mins. The dose will be repeated on study days 4 (post op day 3) and 8 (post op day 7), then every 2 weeks for 5 additional doses. Thereafter, belatacept will be given once every 4 weeks (+/- 3 days) at 10mg/kg through 6 months then at 5mg/kg indefinitely.; Sirolimus will be started on postoperative day 1 at a dose of 2 mg per day orally. Doses will be adjusted to maintain 24-hour trough levels of 8-10ng/ml until the drug is weaned. Toxicity attributable to sirolimus (e.g., mouth ulcers, arthralgias) will prompt dose reduction to address clinical concerns in this regard. If sirolimus trough levels need to be reduced below 4ng/ml to control drug side effects, the patient will be considered intolerant to the drug and will be changed to other medications.; All participants will receive a single dose of 30 mgs of alemtuzumab on the day of transplantation.
Intervention MeSH terms: Sirolimus; Alemtuzumab; Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Acute rejection is a common problem after a kidney transplant. Rejection can occur when the
      kidney recipient's immune system tries to attack (or reject) the new kidney. Rejection
      typically most often develops in the first few months after a transplant.

      This single center study will seek to determine if a new combination of anti-rejection
      medications, including the recently FDA approved drug called Belatacept, is better than the
      current standard anti-rejection drug regimen at preventing rejection. Also to be determined
      will be whether the new combination of drugs will allow participants to wean off their oral
      anti-rejection medications over time.

      This study will test the safety and effectiveness of a new investigational drug combination
      using alemtuzumab, belatacept, and sirolimus when given with or without donor bone marrow.

      This combination of medicines has not been tested before in humans. Alemtuzumab (Campath) is
      approved for use in some types of white blood cell cancers, but is considered investigational
      in transplant patients. Belatacept is now FDA approved and is being studied in transplant
      patients. Sirolimus (Rapamune) is approved for use in transplant patients, but its use with
      belatacept and alemtuzumab is investigational.

      In the initial 20 subjects enrolled in the study, half tested whether an infusion of bone
      marrow from the kidney donor would improve the effect of these drugs. This bone marrow
      infusion was also considered investigational.

      Enrollment of 20 additional subjects began in January, 2013. The donor bone marrow infusion
      has been eliminated. Enrollment was open to primary living and deceased donor kidney
      recipients. Enrollment was closed as of 8/12/2014.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recipients age 18 or older of an HLA-non-identical, living or deceased donor kidney
             transplant.

          -  A willing renal donor who consents for subsequent donation of donor blood for testing
             throughout the follow-up period and for use of his/her kidney in this experimental
             study.

        Exclusion Criteria:

          -  Immunosuppressive drug therapy within 1 year prior to enrollment.

          -  Active malignancy or history of malignancy within 5 years of enrollment.

          -  Any history of blood malignancy or lymphoma.

          -  Any known immunodeficiency syndrome, including HIV infection.

          -  Absence of Epstein-Barr virus (EBV) or cytomegalovirus (CMV) specific antibodies in
             cases with evidence of EBV and/or CMV infection.

          -  Women of child-bearing potential unwilling or unable to use an acceptable method of
             birth control.

          -  Women who are pregnant or breastfeeding at the time of enrollment or study drug
             administration.

          -  Donor age <18 years.

          -  Subjects with protocol-specific etiologies of underlying renal disease.

          -  Subjects with a positive T-cell lymphocytic crossmatch or historical evidence of donor
             specific alloantibody by solid phase or flow-based detection methods.

          -  Prior solid organ transplant or potential to require a concurrent organ or cell
             transplant.

          -  Positive Hepatitis B or C antibodies and polymerase chain reaction (PCR) positive for
             the same.

          -  Active tuberculosis (TB) requiring treatment within the previous 3 years.

          -  Known positive purified protein derivative (PPD) unless chest x-ray is negative or
             treatment for latent TB has been completed.

          -  Active infection or other contraindications.

          -  History of drug or alcohol abuse within the past 5 years.

          -  Psychotic disorders which would interfere with adequate study follow-up.

          -  Active peptic ulcer disease, chronic diarrhea, or gastric malabsorption.

          -  All women 40 years or older with first degree family history of breast cancer will be
             required to have a screening mammogram within 6 months of study enrollment.

          -  Subjects with suspicion of breast malignancy which cannot be ruled out will be
             excluded.

          -  Belatacept use within 30 days prior to the day 1 visit.

          -  Prisoners or individuals who are involuntarily incarcerated.