Belatacept Post Depletional Repopulation to Facilitate Tolerance - Full Text View

Sponsors and Collaborators:	Emory University Bristol-Myers Squibb FDA Office of Orphan Products Development
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00565773

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 one investigational 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 anti-rejection medications over time, and become tolerant.

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 also an investigational drug being studied in transplant patients. Sirolimus (Rapamune) is approved for use in transplant patients, but its use with belatacept and alemtuzumab is investigational.

Half of the patients enrolled in this study will test whether an infusion of bone marrow from the kidney donor will improve the effect of these drugs.

Bone marrow infusion is also considered investigational.

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

Drug Information available for: Alemtuzumab Campath Abatacept

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Use of Belatacept During Post Depletional Repopulation to Facilitate Tolerance in Renal Allograft Recipients

Further study details as provided by Emory University:

Primary Outcome Measures:

The primary endpoint will be the number of patients successfully withdrawn from immunosuppression for one year after their last dose of an immunosuppressive drug.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:	20
Study Start Date:	December 2007
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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 will receive 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) and 15 then every 2 weeks for 4 additional doses. After week 24, belatacept will be given at a dose of 5 mg/kg once every 4 weeks until the drug is weaned. Drug: Alemtuzumab All patients will receive a single dose of 30 mgs. on the day of transplantation. Other: donor bone marrow The bone marrow will be given as an IV infusion over 3 hours on postoperative day 7 (study day 8). The formulated dose will be 1 x 10(8th power) unfractionated nucleated cells/kg recipient ideal body weight. A proposed total of twenty patients will be enrolled in this study. Half of the recipients will be randomized to receive the donor bone marrow infusion. Half of the recipients will not receive the infusion. bone marrow infusion.
2: Experimental 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. This group will not receive an infusion of 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 4 additional doses. After week 24, belatacept will be given as an infusion of 5 mg/kg once every 4 weeks until the drug is weaned. Drug: Alemtuzumab All patients will receive a single dose of 30 mgs. on the day of transplantation.

Arms

Assigned Interventions

1: Experimental

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 will receive 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) and 15 then every 2 weeks for 4 additional doses. After week 24, belatacept will be given at a dose of 5 mg/kg once every 4 weeks until the drug is weaned.

Drug: Alemtuzumab

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

Other: donor bone marrow

The bone marrow will be given as an IV infusion over 3 hours on postoperative day 7 (study day 8). The formulated dose will be 1 x 10(8th power) unfractionated nucleated cells/kg recipient ideal body weight.

A proposed total of twenty patients will be enrolled in this study. Half of the recipients will be randomized to receive the donor bone marrow infusion.

Half of the recipients will not receive the infusion. bone marrow infusion.

2: Experimental

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.

This group will not receive an infusion of 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 4 additional doses. After week 24, belatacept will be given as an infusion of 5 mg/kg once every 4 weeks until the drug is weaned.

Drug: Alemtuzumab

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

Detailed Description:

This study will be a single-center, open-label, randomized, proof of concept study in non-HLA-identical living donor renal transplants.

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 immunosuppressive withdrawal or continue therapy through study close. Sirolimus will first be weaned by halving the dose and/or increasing the dosing interval over a 3 month period.

After sirolimus is discontinued, participants will remain on belatacept alone for 3 additional months. Those still eligible for weaning by pre-defined criteria will then discontinue any further dosing of belatacept.

Follow-up will continue for at least five years. If subjects are successfully weaned from all immunosuppression during their participation in this trial, no other alternative therapy will be warranted. Pending FDA approval of belatacept during the five year course of the study, subjects would be eligible to continue this therapy. If belatacept has not been approved during the course of the study, the Principal Investigator will discuss approved treatment options with the study participants.

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 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.
Positive T-cell lymphocytotoxic crossmatch or a peak PRA >20%.
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

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

Contacts

Contact: Allan D Kirk, M.D.	(404) 727-8380	allan.kirk@emoryhealthcare.org
Contact: Sue Mead, R.N.	(404) 712-1787	sue.mead@emoryhealthcare.org

Locations

United States, Georgia
Emory University Hospital	Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Allan D. Kirk, M.D.
The Emory Clinic	Recruiting
Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Bristol-Myers Squibb

FDA Office of Orphan Products Development

Investigators

Principal Investigator:

Allan D. Kirk, M.D.

Emory University

More Information

Responsible Party:	Emory University ( Allan D. Kirk, M.D. )
Study ID Numbers:	BMS IM103-036
Study First Received:	November 28, 2007
Last Updated:	October 10, 2008
ClinicalTrials.gov Identifier:	NCT00565773
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Study placed in the following topic categories:

Abatacept
Alemtuzumab

Additional relevant MeSH terms:

Immunologic Factors
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs

Antirheumatic Agents
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009