A Pilot Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients
Study Details
Study Description
Brief Summary
The purpose of this study is to assess Alefacept in combination with alemtuzumab induction and calcineurin inhibitor and corticosteroid withdrawal.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This is a single center, investigator initiated, pilot study to assess the safety and efficacy of Alefacept in combination with Alemtuzumab induction and Myfortic with rapid steroid and calcineurin inhibitor withdrawal in de novo Kidney transplant recipients. Induction therapy involves single dose Alemtuzumab and steroids peri-operatively. Tacrolimus will be administered for the first 30 days post-transplantation. Alefacept will be administered IV for the first two doses followed by subcutaneous injections weekly until 12 weeks post-transplant followed by monthly injections for the rest of the duration of the study. The primary outcomes are safety and efficacy outcomes, including biopsy proven acute rejection episodes, infectious complications or other serious adverse events. Secondary outcomes include T-helper differentiation, cytokine production and T regulatory cell generation assessed by immune monitoring assays.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Alefacept (ASP0485) Safety and efficacy of alefacept in combination with alemtuzumab induction and calcineurin inhibitor (CNI) and corticosteroid withdrawal. |
Drug: Alefacept (ASP0485)
Withdrawal of calcineurin inhibitor at 30 days post-transplant. Administer Alefacept 7.5 mg post-op day 0, post-op day 2 given IV; Alefacept 15 mg SQ X 12 weeks, then monthly until Month 12.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Incidence of first biopsy- proven acute rejection (Banff Grade≥ 1) (BCAR rate) and infections [At 12 months post-transplant]
To assess the safety and efficacy of alefacept in combination with a single dose of alemtuzamab induction and Enteric coated Mycophenolic sodium with calcineurin inhibitor withdrawal and rapid elimination of corticosteroids by examining the incidence of first biopsy-proven acute rejection (Banff Grade≥ 1) (BCAR rate) and the incidence and clinical presentation of infections.
Secondary Outcome Measures
- Affect on Immune cells [Up to 12 months post-transplant]
To assess how alefacept affects T-cell differentiation, memory, and immunoregulatory T-cell homeostasis, B-cells and cytokine/chemokine profile by using various immune monitoring assays.
- Assess secondary outcome measures of efficacy and safety [Upto 12 months post-transplant]
At 12 months: Patient/graft survival rates, BCAR rate, Maximum grade of acute rejection with BCAR, Incidence of clinically-treated acute rejections, Incidence of anti-lymphocyte antibody therapy for treatment of rejection, Incidence of multiple rejection episodes, Incidence of treatment failure (defined as death, graft loss, biopsy-confirmed acute rejection, lost to follow-up or early discontinuation of treatment regimen), Incidence of leucopenia, Incidence of bacterial, fungal, viral, or parasitic infection. At 6 & 12 months: Serum creatinine, GFR by iohexol clearance. Time to first BCAR
Eligibility Criteria
Criteria
Inclusion Criteria:
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Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, obtained from the subject or legally authorized representative prior to study-related procedures (including withdrawal of prohibited medication, if applicable)
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Recipient of a kidney from a non-HLA identical related living donor, a non- related living donor, or deceased donor
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Recipient of a de novo kidney transplant
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≥ 18 years of age
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Anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure
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Female subjects of child bearing potential must have a negative urine or serum pregnancy test, and must agree to maintain effective birth control during the study
Healthy donor is eligible for the blood draw if:
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Institutional Review Board (IRB) approved written Informed Consent and Health Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites, or equivalent privacy language as per national regulations, is obtained from subject prior to any study-related procedures
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Subject is a donor to a de novo kidney transplant subject who is enrolled in the study or a self declared healthy volunteer who is not a kidney donor for a subject enrolled in the study
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≥ 18 years of age
Exclusion Criteria:
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Previously received or is receiving an organ transplant other than a kidney
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Sensitivity to iodine
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Will receive a transplant from a non-heart beating donor (donation after cardiac death
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DCD)
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Receives a transplant from an HLA identical related living donor
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Will receive a solitary kidney from a deceased donor < 5 years of age
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Will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours
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Will receive an ABO incompatible donor kidney
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Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)
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Recipient has a positive T or B cell crossmatch by investigational site's standard method of determination. For recipients where a flow cytometry crossmatch is performed and is positive in either T or B cell testing, recipients are excluded only if donor specific, anti-HLA antibody is detected by flow cytometry based, specific anti-HLA antibody testing.
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Current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully
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Significant liver disease
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Serologically negative for cytomegalovirus (CMV) with serologically positive CMV donor
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Serologically negative for Epstein Barr virus
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Has received intravenous immunoglobulin (IVIG) therapy in the three months prior to first dose of study drug
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Uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives
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Concurrently participating in another drug study or has received an investigational drug within 28 days prior to transplant
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Known hypersensitivity to alefacept, alemtuzumab, tacrolimus, mycophenolic acid, corticosteroids, or any of their components
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Any form of substance abuse, psychiatric disorder, or a condition that in the opinion of the Investigator could invalidate communication with the Investigator
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Subject is pregnant or lactating
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Subject is unlikely to comply with the visits scheduled in the protocol
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Subject will receive a kidney transplant from an expanded criteria donor (ECD)
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Will receive a kidney transplant from a CDC high risk donor
Healthy donor subject will be excluded from participation if any of the following apply:
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Unable to comprehend the investigational nature of the protocol participation
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Complete blood count results determined to be outside the normal ranges
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Northwestern Memorial Hospital | Chicago | Illinois | United States | 60611 |
Sponsors and Collaborators
- Northwestern University
- Astellas Pharma Inc
Investigators
- Principal Investigator: M. Javeed Ansari, MD, Northwestern Universiy, Northwestern Memorial Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
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