Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant

NCT00063817 | Completed Phase 1 DMC

• 2 other identifiers: DAIT ITN010STDAIT NKD03
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.

Conditions

End-stage Renal Disease; Renal Transplantation; Kidney Transplantation

Keywords

End-stage renal disease; Renal Transplant; Bone Marrow Transplant; nonmyeloablative conditioning regimen

Outcome Measures

Primary Outcomes (1)

• Graft Survival Twenty-Four Months Post Transplantation

  Defined by kidney transplant survival at month 24 post transplantation with successful withdrawal of cyclosporine following transplantation, in the absence of maintenance immunosuppression.

  24 months (2 Years) Post Transplantation

Secondary Outcomes (5)

• Participant Survival

  Up to thirty-six months (3 Years) Post Transplantation

• Graft Survival

  Up to thirty-six months (3 Years) Post Transplantation

• Change from Baseline in Renal Function Using Serum Creatinine

  Up to thirty-six months (3 Years) Post Transplantation

• Number of Episodes of Acute or Chronic Graft Versus Host Disease (GVHD)

  From Week 1 through thirty-six months (3 Years) Post Transplantation

• Number of Adverse Events

  Participant enrollment through <=thirty-six months (3 Years) Post Transplantation

Study Arms (1)

Conditioning Regimen

EXPERIMENTAL

Cyclophosphamide intravenously (IV) on days -5 and -4 with respect to transplantation; MEDI-507 on days -1, 0, and 1 (after a test dose of 0.1 mg per kg on day -2); and cyclosporine A IV and thymic irradiation on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered daily postoperatively, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Amendment applicable to the 4th and 5th participant: rituximab on days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.

Drug: Conditioning Regimen

Interventions

Conditioning Regimen DRUG

Cyclophosphamide 60 mg per kilogram (kg) of body weight per day intravenously (IV) on days -5 and -4 with respect to transplantation; humanized anti-CD2 monoclonal antibody (MEDI-507) 0.6 mg per kg on days -1, 0, and 1 (after test dose of 0.1 mg per kg on day -2); and cyclosporine A 5 mg per kg IV and thymic irradiation (700 cGy) on day -1. Hemodialysis was performed before and 14 hours after each dose of cyclophosphamide.Kidney transplantation was followed by IV infusion of donor bone marrow. Oral cyclosporine A was administered postoperatively, 8 to 12 mg per kg per day, with target trough blood levels of 250 to 350 ng per milliliter; the dose was tapered and discontinued over a period of several months. Protocol amendment that applied to participant 4 and 5: rituximab, 375 mg per square meter of body-surface area days -7 and -2; and prednisone, 2 mg per kg per day starting on the day of transplantation with tapering over the next 10 days.

Also known as: nonmyeloablative preparative regimen

Conditioning Regimen

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody \[PRA\] greater than 20%) within the 60 days prior to transplant as measured by cytotoxicity assays, ELISA, and flow cytometry;
• Undergoing a first or second transplant;
• Receiving a transplant from a living related donor who is ABO (blood type) compatible and haploidentical (3, 4, or 5 antigen match by serologic typing);
• Cardiac ejection fraction greater than 40%;
• Forced expiratory volume (FEV1) greater than 50%;
• Liver function tests, bilirubin, and coagulation studies less than 2 X normal;
• White blood cells greater than 2000/mm\^3; abd
• Platelets greater than 100,000/mm\^3

You may not qualify if:

• Positive donor lymphocyte cross-match;
• HIV-1 infected;
• Positive hepatitis B surface antigen (HbsAg);
• Hepatitis C virus infected;
• History of cancer;
• Prior dose-limiting radiation therapy;
• Pregnant, breastfeeding, or planning pregnancy within the time frame of the study;
• Enrolled in another investigational drug study within 30 days prior to study entry; or
• Receiving maintenance immunosuppression within 3 months before the conditioning regimen begins

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.

  PMID: 18216355 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases website
• Click here for the Immune Tolerance Network website

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Transplantation Conditioning

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• David H. Sachs, MD

  Department of Medicine, Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• A. Benedict Cosimi, MD

  Department of Medicine, Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2003
• First Posted: July 8, 2003
• Study Start: June 1, 2003
• Primary Completion: January 1, 2009
• Study Completion: July 1, 2009
• Last Updated: December 27, 2017

Record last verified: 2017-12

Locations

US (1)