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Belatacept Post Depletional Repopulation to Facilitate Tolerance

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Emory University
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Antonio Guasch, M.D., Emory University
ClinicalTrials.gov Identifier:
NCT00565773
First received: November 28, 2007
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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 is open to primary living and deceased donor kidney recipients.

Funding Source - FDA OOPD


Condition Intervention Phase
Organ Transplantation
Drug: Belatacept
Drug: Alemtuzumab
Other: donor bone marrow
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of Belatacept During Post Depletional Repopulation to Facilitate Tolerance in Renal Allograft Recipients

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • The primary endpoint will be the number of patients successfully withdrawn from oral immunosuppression for one year after their last dose of an immunosuppressive drug. [ Time Frame: Prospective ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of proposed therapies to prevent acute and/or chronic rejection by 1,3, and 5 years compared to the standard reported in the UNOS database for patients with similar demographics. [ Time Frame: Prospective ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: December 2007
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

All patients will be given a single dose of alemtuzumab on the day of transplantation. All patients will receive belatacept and sirolimus for 1 year.

Ten patients in the first group of 20 subjects received a single dose of donor bone marrow 7 days after transplantation.

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.

Drug: Belatacept
Belatacept will be given as an IV infusion of 10mg /kg over 30 minutes. This will be repeated on study days 4 and 8 (prior to bone marrow infusion in the first group of subjects) and 15 then every 2 weeks for 5 additional doses. After week 24, belatacept will be given at a dose of 5 mg/kg once every 4 weeks indefinitely.
Other Names:
  • LEA29Y
  • Nulojix
Drug: Alemtuzumab
All patients will receive a single dose of 30 mgs. on the day of transplantation.
Other Name: CAMPATH
Other: donor bone marrow

The bone marrow was given as an IV infusion over 3 hours on postoperative day 7 (study day 8) in the initial group of 20 randomized subjects. The formulated dose was 1 x 10(8th power) unfractionated nucleated cells/kg recipient ideal body weight.

A proposed total of forty patients will be enrolled in this study. Enrollment was reopened last year to include 20 additional living or deceased donor kidney recipients.

Half of the first 20 recipients were randomized to receive a single donor bone marrow infusion. Half did not receive the infusion. Donor bone marrow infusion in the second group of 20 subjects has been eliminated.

Experimental: 2

All patients will be given a single dose of alemtuzumab on the day of transplantation. All patients will receive belatacept and sirolimus for one year.

Half of the initial 20 subjects did not receive an infusion of donor bone marrow. None of the additional 20 subjects in the second group will receive donor bone marrow.

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.

Drug: Belatacept
Belatacept will be given as an IV infusion at 10mg/kg over 30 minutes on the day of transplantation. This dose will be repeated on study days 4, 8, and 15, then every 2 weeks for 5 additional doses. After week 24, belatacept will be given as an infusion of 5 mg/kg once every 4 weeks indefinitely.
Other Names:
  • LEA29Y
  • Nulojix
Drug: Alemtuzumab
All patients will receive a single dose of 30 mgs. on the day of transplantation.
Other Name: CAMPATH

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565773

Contacts
Contact: Antonio Guasch, MD 404-727-2522 aguasch@emory.edu
Contact: Ada Ghali, R.N. (404) 712-9845 ada.ghali@emoryhealthcare.org

Locations
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Antonio Guasch, MD         
The Emory Clinic Recruiting
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Bristol-Myers Squibb
Investigators
Principal Investigator: Antonio Guasch, MD Emory University
  More Information

No publications provided by Emory University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Antonio Guasch, M.D., Professor, Emory University
ClinicalTrials.gov Identifier: NCT00565773     History of Changes
Other Study ID Numbers: IRB00005064, Grant # FD-R-003539, eIRB 00005064, BMS IM103-036
Study First Received: November 28, 2007
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Alemtuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014