Allogeneic Blood Stem Cell Transplantation for Patients With Life-Threatening Systemic Lupus Erythematosus (SLE)

August 11, 2023 updated by: Stanford University

Allogeneic Hematopoietic Cell Transplantation for Patients With Life-Threatening Systemic Lupus Erythematosus Using a Non-Myeloablative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin

The Stanford Medical Center Division of Immunology and Rheumatology and the Division of Blood and Marrow Transplantation (BMT) are enrolling patients with severe systemic lupus erythematosus (SLE) that is resistant to standard treatment (prednisone and cyclophosphamide [Cytoxan]) into a new study to determine if they can be successfully treated with a blood stem cell transplantation obtained from an appropriate donor. Donors will be human leukocyte antigen (HLA)-matched healthy brothers or sisters. For patients without sibling HLA-matches, a search for donors will be initiated through the US and International Donor Registries. Eligible patients must be at least 18 years old and have SLE with progressive kidney, lung, heart, or central nervous system disease that has not responded to standard therapy.

Patients will be treated for two weeks to prepare them for the infusion of blood stem cells that are obtained from their HLA-matched donor. Patients will initially be treated with immunosuppressive drugs, which will be gradually withdrawn at approximately 6 months after transplantation. The goal of this study is to replace the abnormal immune cells of the SLE affected patient that causes the disease with normal immune cells that are generated from the transplant blood stem cells from the healthy donor.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to evaluate the effectiveness of allogeneic blood stem cell transplantation in individuals with life-threatening SLE. A non-bone marrow ablative regimen consisting of total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) will be used to condition the recipients for transplantation. Appropriately HLA-matched donors will undergo "mobilization" of their peripheral blood mononuclear cells using G-CSF and collection by apheresis.

The preparative regimen will consist of targeted low dose radiation of lymphoid tissue administered over a 2-week period of time. During the first week of irradiation, the patients will also receive the ATG treatment. Patients will be admitted to the in-patient service for the first 5 days of the transplant preparative regimen while receiving the ATG infusion. Patients will be discharged for the second half of the preparative regimen and followed in the out-patient clinic thereafter. Patients will start immunosuppressive treatment with cyclosporine and mycophenolate mofetil prior to the infusion of mobilized peripheral blood stem cells. The mycophenolate mofetil will be stopped at approximately 1 month post-transplantation and the cyclosporine will be tapered beginning at 2 months post-transplantation and discontinued by 6 months in the presence of stable blood chimerism and the absence of graft-versus-host disease. In the pre-transplant and post-transplant setting, patients will be evaluated by an integrated team of Rheumatology and BMT physicians. During the first 21-28 days post-transplantation, these evaluations will be performed on a daily or every other day basis. Patients will be clinically assessed and evaluated for engraftment of donor cells and disease response. Patients will then be followed as needed with maximum time between evaluations of 1 to 2 weeks in the first 100 days, and then monthly for 6 months and every 6 months to 12 months thereafter.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Meet the American College of Rheumatology (ACR) criteria for classification of SLE (i.e., at least 4 of the 11 criteria; see Appendix 2 of the protocol for more information)
  • SLE disease activity index (SLEDAI) greater than 20 (i.e., active, multi-system SLE; see Appendix 3 of the protocol for more information)

  • History of one or more of the following conditions that have not responded to conventional therapy with pulse intravenous or oral cyclophosphamide and corticosteroids:

    1. Lupus pneumonitis with a progressive decline in lung function tests and evidence of oxygen desaturation on effort in which the lung CT scans and chest X-rays show active disease without irreversible extensive scarring
    2. Diffuse alveolar hemorrhage associated with oxygen desaturation with persistent abnormalities of the lung CT scan or X-rays that have not resolved after conventional therapy
    3. Central nervous system lupus that has resulted in neurological deficits requiring hospitalization with a brain CT scan and/or brain MRI and shows evidence of lupus activity without extensive irreversible lesions
    4. Lupus nephritis with a progressive decline in the creatinine clearance that has not fallen below 25 ml/min in which a biopsy shows active disease without irreversible extensive scarring

  • Refractory disease, as determined by failure of the following two conditions:

    1. Trial of corticosteroids (equivalent to prednisone 0.5 mg/kg/day for 2 months and/or at least 3 pulses of methylprednisolone 1,000 mg over 3 days) on at least one occasion within the 6 months prior to study entry
    2. Trial of cyclophosphamide of at least 500 mg/m² IV pulse at least 3 times or oral cyclophosphamide for at least 30 days
  • Must have a fully HLA identical sibling or a matched unrelated donor
  • Willing to use contraception throughout the study and for 12 months following treatment

Exclusion Criteria:

  • Allergic to rabbit ATG
  • Score of less than 60% on Karnofsky Performance Scale

  • Organ dysfunction, defined as follows:

    1. Cardiac function ejection fraction less than 40% or uncontrolled malignant arrhythmias or clinical evidence of congestive heart failure (New York Class 3-4, see Appendix 4 of the protocol for more information)
    2. Pulmonary diffusion capacity (DLCO) less than 30% of predicted
    3. Liver function abnormalities with direct bilirubin levels greater than 3.0 mg/dL on two repeated tests and/or transaminases greater than 4 times the upper limit of normal
    4. Measured creatinine clearance of less than 40 ml/min (24 hour urine collection)
  • Pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hematopoietc Stem Cell Transplant
Hematopoietic Cell Transplantation. Total body irradiation and Stem cell infusion in life threating lupus patients
Drug: Hematopoietic Cell Transplantation
1200 cGy total lymphoid irradiation (TLI) are administered on day -11 through -7 and days -4 through -1 pretransplantation; rabbit ATG at 1.5 mg/kg i.v. on days -11 through -7 pretransplantation; one single infusion of donor CD34+ cells plus selected T cell add back on completion of TLI (day 0); mycophenolate mofetil (MMF) is begun on day 0 at a dose of 15 mg/kg bid and stopped on day +28; cyclosporine (CSP) at initial dose of 6.25 mg/kg and adjusted to maintain trough blood levels of 350-500 ng/ml is begun on day -3 to complete withdrawal by 6 months post-transplantation.
Other Names:
  • NCT00325741

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to achieve complete remission (participants that are off all immunosuppressive therapy without clinical or laboratory evidence of active disease)
Time Frame: Measured within the first year
Measured within the first year

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients with stable chimerism in all blood and immune cell lineages
Time Frame: Measured within the first year
Measured within the first year
Percentage of participants with acute or chronic graft-versus-host disease
Time Frame: Measured within the first year
Measured within the first year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
City of Hope National Medical Center

Investigators

  • Principal Investigator: Judith A. Shizuru, MD, PhD, Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2004

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

May 12, 2006

First Submitted That Met QC Criteria

May 12, 2006

First Posted (Estimated)

May 15, 2006

Study Record Updates

Last Update Posted (Actual)

August 15, 2023

Last Update Submitted That Met QC Criteria

August 11, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 368
  • P01HL075462-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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