Belatacept Post Depletional Repopulation to Facilitate Tolerance

• Status: Completed
• Trial end date: 2017-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Allan D Kirk, MD, PhD; Emory University
• Collaborators: Bristol-Myers Squibb; Duke University
• Treatments: Abatacept; Alemtuzumab; Methylprednisolone; Sirolimus

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.