Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, patients must take immunosuppressants to prevent rejection. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for immunosuppressants. Patients in this study received a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, patients underwent a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that had not been approved by the FDA. This is a phase I study; the primary goal of the trial was to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study was also meant to determine whether patients with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation. Patients were assessed before and after transplantation and were actively followed for 24 months. Patients were monitored for graft rejection and medication toxicity. After Month 24, the study continued with an additional 36 months of medical record-based surveillance.

Plan to Share IPD: Yes Plan Description: Data access is provided in TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

instance of dataset

available with registration

PART

National Institute of Allergy and Infectious Diseases (NIAID)

Drug: hOKT3gamma1(Ala-Ala) Escalating dose given IV over 5 days (1mg, 2mg, 4mg on days 3-5) of each 28 day cycle Other Name: anti-CD3 monoclonal antibody Drug: Placebo Intravenous dose of placebo given over 5 days of each 28 day cycle Other Name: Placebo comparator

registration required

Arthritis, Psoriatic

Marcus Clark, MD

University of Chicago

Principal Investigator

Treatment of Psoriatic Arthritis with hOKT3γ1 (Ala-Ala)

4

Proportion of Participants Who Received at Least Two Cycles of Treatment and Who Showed Predefined Levels of Improvement in Primary Efficacy Parameter at Six Months [ Time Frame: 6 Months ] Participants who improve by at least 1 unit from baseline in either the physician or participant global assessment and have at least 30% improvement from baseline in either tender or swollen joint scores[1] at 6 months from start of treatment and received at least 2 cycles of treatment The tender and swollen joint scores assess 68 and 66 joints, respectively, with each joint rated from 0 to 3. Total scores range from 0-204 for tenderness and 0-198 for swelling, with higher scores indicating more severe symptoms[2]. Ref: Clegg DO et al. Arthritis Rheum. 1996; 39(12):2013-20.

Not Provided

NC

Inclusion Criteria: Diagnosis of psoriatic arthritis. Participants do not need to have concurrent psoriasis to participate in the study; Active inflammation in 3 or more joints; Currently receiving ongoing therapy with methotrexate or azathioprine; and Willing to use acceptable forms of contraception. Exclusion Criteria: Active infection with HIV, hepatitis C virus, or hepatitis B virus; Uncompensated heart failure or a recent myocardial infarction (heart attack) within the 6 months prior to study entry; Certain other serious illnesses or cancers; Participation in another clinical trial within the 6 weeks prior to study entry; or Pregnant or breastfeeding.

2006-12-01

Treatment of Psoriatic Arthritis With hOKT3γ1 (Ala-Ala)

Experimental: hOKT3gamma1 (Ala-Ala) Escalating dose of hOKT3gamma1 (Ala-Ala) given intravenously over 5 days of each 28 day cycle Intervention: Drug: hOKT3gamma1(Ala-Ala) Placebo Comparator: Placebo Intravenous dose of placebo given over 5 days of each 28 day cycle Intervention: Drug: Placebo

hOKT3gamma1 (Ala-Ala) is a man-made antibody that is commonly used to prevent organ rejection. The purpose of this study is to determine whether hOKT3gamma1 (Ala-Ala) is safe and effective in psoriatic arthritis patients who are unable to control their arthritis with methotrexate or azathioprine.

Psoriatic arthritis is a form of inflammatory arthritis that affects approximately 7% of people who have psoriasis. Treatment typically include drugs such as methotrexate, azathioprine, and etanercept, which suppress the immune system in a nonspecific fashion in an attempt to control the immune responses causing the disease. In some severe cases of psoriatic arthritis, these drugs cannot adequately control the disease, often requiring patients to undergo continuous treatment to prevent or combat disease activity. hOKT3gamma1 (Ala-Ala) is a genetically engineered monoclonal antibody directed against the CD3 antigen on T cells. hOKT3gamma1 (Ala-Ala) specifically targets immune cells that are actively involved in destructive immune responses, such as those that cause psoriatic arthritis. In a small pilot study of eight people with psoriatic arthritis who received a 2-week course of hOKT3gamma1 (Ala-Ala), the drug appeared safe and caused no serious side effects. This study will test the safety and efficacy of hOKT3gamma1 (Ala-Ala) in alleviating symptoms in psoriatic arthritis patients. This study will last 2 years. Individuals with psoriatic arthritis who are receiving methotrexate or azathioprine therapy and have active disease are eligible to participate. Participants will be randomly assigned to receive hOKT3gamma1 (Ala-Ala) or placebo. Participants will receive a 5-day treatment with the drug or placebo every month for the first 4 months of the study. There will be 5 study visits over 2 years to assess the safety and effectiveness of hOKT3gamma1 (Ala-Ala) and to evaluate laboratory measures related to the underlying immune problems that cause psoriatic arthritis.

Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Outcomes Assessor) Primary Purpose: Treatment

United States

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