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

NCT00325741 | Terminated Phase 1 DMC

• 2 other identifiers: 368P01HL075462-02
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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 Patients will initially be treated with immunosuppressive drugs, which will be gradually withdrawn at approximately 6 months after transplantation.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.

Conditions

Lupus Erythematosus, Systemic

Keywords

Lupus; Systemic Lupus Erythematosus; Blood Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Time to achieve complete remission (participants that are off all immunosuppressive therapy without clinical or laboratory evidence of active disease)

  Measured within the first year

Secondary Outcomes (2)

• Percentage of patients with stable chimerism in all blood and immune cell lineages

  Measured within the first year

• Percentage of participants with acute or chronic graft-versus-host disease

  Measured within the first year

Study Arms (1)

Hematopoietc Stem Cell Transplant

EXPERIMENTAL

Hematopoietic Cell Transplantation. Total body irradiation and Stem cell infusion in life threating lupus patients

Drug: Hematopoietic Cell Transplantation

Interventions

Hematopoietic Cell Transplantation DRUG

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.

Also known as: NCT00325741

Hematopoietc Stem Cell Transplant

Eligibility Criteria

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

You may qualify if:

• 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:
• 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
• 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
• 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
• 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:
• 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
• 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

You may not qualify if:

• Allergic to rabbit ATG
• Score of less than 60% on Karnofsky Performance Scale
• Organ dysfunction, defined as follows:
• 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)
• Pulmonary diffusion capacity (DLCO) less than 30% of predicted
• 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
• Measured creatinine clearance of less than 40 ml/min (24 hour urine collection)
• Pregnant

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• City of Hope National Medical Center: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Judith A. Shizuru, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 12, 2006
• First Posted: May 15, 2006
• Study Start: June 1, 2004
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: August 15, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)