Belatacept Post Depletional Repopulation to Facilitate Tolerance
| Status: | Active, not recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/30/2019 |
| Start Date: | December 2007 |
| End Date: | August 2019 |
Use of Belatacept During Post Depletional Repopulation to Facilitate Tolerance in Renal Allograft Recipients
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 was begun in January, 2013. The donor bone marrow
infusion has been eliminated. Enrollment was open to primary living and deceased donor kidney
recipients. Enrollment is closed as of 8/12/2014.
Funding Source - FDA OOPD
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 was begun in January, 2013. The donor bone marrow
infusion has been eliminated. Enrollment was open to primary living and deceased donor kidney
recipients. Enrollment is closed as of 8/12/2014.
Funding Source - FDA OOPD
This study will be a single-center, open-label,proof of concept study in non-HLA-identical
living and deceased donor renal transplants. The initial 20 subjects were randomized to
either receive/not to receive a single donor bone marrow infusion in addition to the
investigational combination of alemtuzumab, belatacept, and sirolimus. Since the bone marrow
infusion has been eliminated in the second group of 20 subjects, no randomization will be
required. All recipients in the second group of 20 subjects will receive the same
investigational combination of alemtuzumab, belatacept, and sirolimus.
At the time of transplant, participants will receive a 3-hour IV infusion of 30 mg. of
alemtuzumab. Participants will receive a combination of sirolimus and belatacept for at least
1 year. At that time, eligible participants will consent to and begin oral immunosuppressive
withdrawal or continue therapy through study close. Sirolimus will first be weaned by halving
the dose and/or increasing the dosing interval over at least a 2-6 month period. After
sirolimus is discontinued, participants will remain on monthly IV belatacept monotherapy
indefinitely.
Follow-up will continue for at least five years. If subjects are successfully weaned from
oral immunosuppression during their participation in this trial, no other alternative therapy
will be warranted. Since belatacept is now FDA approved, subjects will be eligible to
continue this therapy after their study participation has ended.
living and deceased donor renal transplants. The initial 20 subjects were randomized to
either receive/not to receive a single donor bone marrow infusion in addition to the
investigational combination of alemtuzumab, belatacept, and sirolimus. Since the bone marrow
infusion has been eliminated in the second group of 20 subjects, no randomization will be
required. All recipients in the second group of 20 subjects will receive the same
investigational combination of alemtuzumab, belatacept, and sirolimus.
At the time of transplant, participants will receive a 3-hour IV infusion of 30 mg. of
alemtuzumab. Participants will receive a combination of sirolimus and belatacept for at least
1 year. At that time, eligible participants will consent to and begin oral immunosuppressive
withdrawal or continue therapy through study close. Sirolimus will first be weaned by halving
the dose and/or increasing the dosing interval over at least a 2-6 month period. After
sirolimus is discontinued, participants will remain on monthly IV belatacept monotherapy
indefinitely.
Follow-up will continue for at least five years. If subjects are successfully weaned from
oral immunosuppression during their participation in this trial, no other alternative therapy
will be warranted. Since belatacept is now FDA approved, subjects will be eligible to
continue this therapy after their study participation has ended.
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 EBV or 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 PCR positive for the same.
- Active (tuberculosis) TB requiring treatment within the previous 3 years.
- Known positive 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.
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2
sites
Emory University Hospital As the largest health care system in Georgia and the only health...
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