HLA-Identical Sibling Renal Transplant Tolerance

NCT ID: NCT00619528

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2023-09-30

Brief Summary

The purpose of this study is to attempt to eliminate the necessity of immunosuppressive therapy for HLA-identical sibling Kidney Transplants, examine cellular chimerism of donor hematopoietic stem cell (DHSC) lineages for pairs to demonstrate immunologic unresponsiveness, and to investigate the safety and efficacy of the treatment regimen including withdrawal of immunosuppression after one year post-transplant for those recipients having received DHSC infusions.

Detailed Description

Primary Study Objectives:

1. To remove all immunosuppressive therapy from recipients of HLA-identical sibling renal transplants within 24 months of transplantation.

2. To detect and follow cellular (macro) chimerism of donor hematopoietic stem cell (DHSC) lineages and the generation of T-regulatory cells using specialized immunomonitoring assays for these donor/recipient pairs to demonstrate specific immunologic unresponsiveness.

3. To investigate the safety and efficacy of a treatment regimen consisting of induction therapy with Campath-1H and steroid-free low dose maintenance immunosuppression, consisting of mycophenolate mofetil (MMF) and tacrolimus converted to sirolimus. This is to be followed by complete withdrawal of immunosuppression beginning at one year, at a minimum, post transplant, in recipients who have also been given four infusions of purified donor hematopoietic Cluster of Differentiation (CD)34+ stem cells (DHSC).

Conditions

Immunosuppression; Kidney Transplantation; Graft Rejection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

No separate arms: All Enrolled Receive Same Treatment

Group Type: EXPERIMENTAL

Infusion of Donor Hematopoietic Stem Cells and Campath-1H

Intervention Type: BIOLOGICAL

Intervention: a four-dose (peri-operative and 3, 6, and 9-month boost) DHSC infusion protocol using two-dose Campath-1H induction combined with transient (conditioning) Tacrolimus/Sirolimus and MMF therapy will result in a high degree of macro-chimerism (\>10%), and a robust prolonged donor-specific (post-thymic) immunoregulatory condition that will allow renal transplant survival in the absence of permanent immunosuppression.

Interventions

Infusion of Donor Hematopoietic Stem Cells and Campath-1H

Intervention: a four-dose (peri-operative and 3, 6, and 9-month boost) DHSC infusion protocol using two-dose Campath-1H induction combined with transient (conditioning) Tacrolimus/Sirolimus and MMF therapy will result in a high degree of macro-chimerism (\>10%), and a robust prolonged donor-specific (post-thymic) immunoregulatory condition that will allow renal transplant survival in the absence of permanent immunosuppression.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patient fully informed, signed dated Institutional Review Board (IRB)-approved informed consent form obtained directly by the P.I., Co-P.I., or Res. Nurse, and willing to follow study procedures for the duration of study (3 yrs).
• Recipient: a hematocrit of ≥ 33%, and a hemoglobin of ≥ 11.0 g/dL.
• Weight > 40 kg.
• Primary renal allograft: living related (HLA-identical donor-recipient sibling pairs)
• Negative B-cell and T-cell cytotoxic cross-match, and a low (≤ 10%) Panel Reactive Antibody (PRA) using cytotoxicity.
• Women of childbearing potential: negative qualitative serum pregnancy test.
• Patients studied equivalently as available for transplant using criteria, w/out regard to gender, race, or ethnicity.
• Normal echocardiogram w/ ejection fraction >50%.
• Male participants w/ reproductive potential agree to use approved methods of birth control during treatment w/ Campath-1H and for minimum of 6 months following last dose. Female participants of childbearing potential agree to use approved methods of birth control for duration of participation in study.
• Patient agrees to follow-up every 2 months after year 3, up to 10 years.

Exclusion Criteria

• Patient previously received/receiving transplant other than kidney.
• Patient receiving ABO (blood type) incompatible donor kidney.
• Recipient/donor is ELISA positive for human immunodeficiency virus (HIV), antibody positive for hep. C, or surface antigen positive for hep. B.
• Patient has current malignancy or history of malignancy (within past 5 years), except non-metastatic basal or squa¬mous cell carcinoma of the skin, or carcinoma in situ of the cervix that has been treated successfully.
• Patients w/ significant liver disease, defined as having during past 28 days continuously elevated aspartate aminotransferase (AST (SGOT)) and/or Alanine Aminotransferase (ALT (SGPT)) levels greater than 3 times the upper value of the normal range at this center.
• Patient has uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer or other unstable medical condition that could interfere w/ study objectives.
• Patient currently receiving investigational drug or received an investigational drug within 30 days pre-transplant.
• Patient currently receiving immunosuppressive agent.
• In investigator's judgment, anticipated that patient unable to take medications orally or via nasogastric tube by morning of second day (i.e., skin closure).
• Concurrent use of warfarin, fluvastatin, astemizole, pimozide, cisapride, terfenadine, or ketoconazole.
• Patient hypersensitivity to tacrolimus, Campath-1H, Thymoglobulin, daclizumab (Zenapax®), sirolimus, MMF or corticosteroids.
• Patient pregnant or lactating.
• Patients w/ screening/baseline total white blood cell count <4000/mm3; platelet count <100,000/mm3; fasting triglycerides >400 mg/dl (>4.6 mmol/L); fasting total cholesterol >300 mg/dl (>7.8 mmol/L); fasting HDL-cholesterol <30 mg/dl; fasting LDL-cholesterol >200 mg/dl.
• Patient unlikely to comply w/ visits.
• Patient w/ any form of substance abuse, psychiatric disorder or condition that, in investigator's opinion, may invalidate communication.
• Expected that tacrolimus cannot be instituted for over 5 days post-operatively.
• Patients w/ cytotoxic PRA value >10% any time pre-enrollment.
• Patients w/ Graves disease, unless previously treated w/ radioiodine ablative therapy.
• History of idiopathic thrombocytopenic purpura (ITP) or thrombotic thrombocytopenic purpura (TTP)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Joseph Leventhal

Professor, Department of Surgery, Division of Organ Transplantation, Feinberg School of Medicine; Director, Kidney Pancreas Program, Comprehensive Transplant Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph Leventhal, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern Memorial Hospital

Chicago, Illinois, United States

Countries

United States

References

Leventhal JR, Mathew JM, Salomon DR, Kurian SM, Friedewald JJ, Gallon L, Konieczna I, Tambur AR, Charette J, Levitsky J, Jie C, Kanwar YS, Abecassis MM, Miller J. Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers. Am J Transplant. 2016 Jan;16(1):221-34. doi: 10.1111/ajt.13416. Epub 2015 Jul 30.

Reference Type: DERIVED

PMID: 26227106 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01DK025243

Identifier Type: NIH

Identifier Source: secondary_id

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2R01DK025243-25A2

Identifier Type: NIH

Identifier Source: org_study_id

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