HLA-Identical Sibling Renal Transplant Tolerance

NCT00619528 | Completed Results DMC

• 2 other identifiers: 2R01DK025243-25A2R01DK025243
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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.

Conditions

Immunosuppression; Kidney Transplantation; Graft Rejection

Keywords

Transplants; Kidney Transplantation; Immunosuppression; HLA Antigens; Stem Cells; Bone Marrow

Outcome Measures

Primary Outcomes (2)

• The Ability to Withdraw Immunosuppression as Above 24 Months Post-transplant

  The ability to withdraw immunosuppression as above 24 months post-transplant with follow-up to 10 years.

  24 months post-transplant with follow-up to 10 years

• Patient and Graft Survival

  Patient and graft survival measured at the one-year timepoint post-transplant.

  One Year

Study Arms (1)

Experimental

EXPERIMENTAL

No separate arms: All Enrolled Receive Same Treatment

Biological: Infusion of Donor Hematopoietic Stem Cells and Campath-1H

Interventions

Infusion of Donor Hematopoietic Stem Cells and Campath-1H 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.

Experimental

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwestern University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• 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.

  PMID: 26227106 DERIVED

MeSH Terms

Interventions

Alemtuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

20 Donor Recipient Pairs were enrolled (n=40) In addition, 19 controls and 29 parents were also enrolled. This study was concluded earlier than anticipated due to changes in funding support, which impacted the ability to meet all originally stated enrollment goals.

Results Point of Contact

• Title: Joseph Leventhal MD, PhD
• Organization: Northwestern University

jleventh@nm.org

312-695-0427

Study Officials

• Joseph Leventhal, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Surgery, Division of Organ Transplantation, Feinberg School of Medicine; Director, Kidney Pancreas Program, Comprehensive Transplant Center

Study Record Dates

• First Submitted: February 8, 2008
• First Posted: February 21, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2022
• Study Completion: September 1, 2023
• Last Updated: February 27, 2026
• Results First Posted: August 11, 2025

Record last verified: 2026-02

Locations

US (1)