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Organ TransplantationPhase 2NCT00565773

Belatacept Post Depletional Repopulation to Facilitate Tolerance

A Phase 2 study testing Belatacept, Sirolimus and Alemtuzumab in people with Organ Transplantation, run by Allan D Kirk, MD, PhD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Organ Transplantation
What is being tested?
Belatacept, Sirolimus and Alemtuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
Dec 2007to 1 Jul 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 22Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • The Emory Clinic

    Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: 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.

Read more

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.

Read the detailed description

This study will be a single-center, open-label,proof of concept study in non-human leukocyte antigen (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 was 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 one 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.

Being tested
Belatacept, Sirolimus, Alemtuzumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelataceptDrug

    Also called LEA29Y, Nulojix

    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.

  • SirolimusDrug

    Also called Rapamycin

    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.

  • AlemtuzumabDrug

    Also called Campath, Lemtrada

    All participants will receive a single dose of 30 mgs of alemtuzumab on the day of transplantation.

Study groups in NCT00565773
Study groupRoleWhat they receive
Immunosuppressive medicationsExperimentalRenal transplant recipients will be given an experimental combination of immunosuppressive drugs. Participants will receive a single dose of alemtuzumab on the day of transplantation and will receive belatacept and sirolimus for 1 year. At the time of transplant, all patients will receive a single dose of 500 mg of methylprednisolone IV over 30 minutes, followed within 1 hour by an IV infusion of 30 mg of alemtuzumab over 3 hours.
Receives: Drug: Belatacept; Drug: Sirolimus; Drug: Alemtuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Successfully Withdrawn From Oral Immunosuppression

    The primary endpoint is the number of patients successfully withdrawn from oral immunosuppression (sirolimus) for one year after their last dose of sirolimus. After taking sirolimus for one year, participants meeting certain pre-specified criteria were offered the opportunity to wean from sirolimus and continue with belatacept monotherapy. To be eligible for weaning of sirolimus, participants were required to have a kidney biopsy negative for all signs of rejection, including borderline findings.

    Measured: Year 2

Secondary outcomes (6)

  1. Number of Participants Experiencing Costimulation Blockade-resistant Rejection (CoBRR)

    Assessment of the proposed therapies to prevent biopsy proven acute rejection, also known as CoBRR, was determined by the number of participants experiencing CoBRR at 1, 3 and 5 years post-transplant.

    Measured: Year 1, Year 3, Year 5

  2. Number of Participants Experiencing Chronic Allograft Nephropathy (CAN)

    Assessment of biopsy proven chronic allograft nephropathy at 1, 3 and 5 years post-transplant is presented as the number of participants experiencing CAN.

    Measured: Year 1, Year 3, Year 5

  3. Number of Participants With BK Viremia

    The number of participants experiencing BK viremia, an opportunistic infection, during the study is presented here.

    Measured: Up to Year 5

  4. Number of Participants Developing Donor-specific Alloantibody (DSA)

    Long term assessment of donor-specific immune responsiveness after prolonged therapy with belatacept (with or without sirolimus), and during and following drug withdrawal as determined by in vitro alloresponsiveness in carboxyfluorescein succinimidyl ester (CFSE) mixed lymphocyte reactivity and intracellular cytokine staining (ICCS).

    Measured: Up to Year 5

  5. Number of Participants With Surviving Grafts

    The number of participants whose grafts survived without graft failure at each follow up time point is presented here.

    Measured: Year 1, Year 3, Year 5

  6. Estimated Glomerular Filtration Rate (eGFR)

    Graft function was assessed throughout the study by the estimated glomerular filtration rate. The eGFR indicates the percentage of kidney function that a person has based on creatinine, age, body size, and gender. An eGFR of below 60 indicates chronic kidney disease. A higher eGFR means that there is greater kidney function.

    Measured: Year 1, Year 3, Year 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2007 (estimated)
  2. Study startDec 2007
  3. Primary completion1 Jul 2017
  4. Study completion1 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00565773
Sponsor's protocol ID
IRB00005064
Other IDs
Grant # FD-R-003539, BMS IM103-036
Status last verified
Jan 2020
First submitted
28 Nov 2007
Last updated
11 Feb 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Xu H, Mehta AK, Gao Q, Lee HJ, Ghali A, Guasch A, Kirk AD. B cell reconstitution following alemtuzumab induction under a belatacept-based maintenance regimen. Am J Transplant. 2020 Mar;20(3):653-662. doi: 10.1111/ajt.15639. Epub 2019 Nov 13.

    PubMed 31596034

  • Xu H, Bendersky VA, Brennan TV, Espinosa JR, Kirk AD. IL-7 receptor heterogeneity as a mechanism for repertoire change during postdepletional homeostatic proliferation and its relation to costimulation blockade-resistant rejection. Am J Transplant. 2018 Mar;18(3):720-730. doi: 10.1111/ajt.14589. Epub 2017 Dec 12.

    PubMed 29136317

  • Xu H, Samy KP, Guasch A, Mead SI, Ghali A, Mehta A, Stempora L, Kirk AD. Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients. Am J Transplant. 2016 Feb;16(2):550-64. doi: 10.1111/ajt.13469. Epub 2015 Oct 5.

    PubMed 26436448

  • Kirk AD, Guasch A, Xu H, Cheeseman J, Mead SI, Ghali A, Mehta AK, Wu D, Gebel H, Bray R, Horan J, Kean LS, Larsen CP, Pearson TC. Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors. Am J Transplant. 2014 May;14(5):1142-51. doi: 10.1111/ajt.12712. Epub 2014 Mar 31.

    PubMed 24684552

  • Xu H, Lee HJ, Schmitz R, Shaw BI, Li S, Kirk AD. Age-related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients. Am J Transplant. 2021 Sep;21(9):3163-3174. doi: 10.1111/ajt.16625. Epub 2021 May 20.

    PubMed 33942491

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belatacept, Sirolimus and Alemtuzumab in people with Organ Transplantation, run by Allan D Kirk, MD, PhD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Successfully Withdrawn From Oral Immunosuppression (time frame: Year 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00565773, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2020.

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