Clinical Trial: Lymphocyte Depletion and Stem Cell Transplantation to Treat Severe Systemic Lupus Erythematosus

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study of Intensified Lymphodepletion Followed by Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Systemic Lupus Erythematosus

Brief Summary:

This study will examine a new approach to treating patients with severe systemic lupus erythematosus (SLE) that involves collecting stem cells (cells produced by the bone marrow that develop into blood cells) from the patient, completely shutting down the patient's immune system, and then giving back the patient's stem cells. SLE is a chronic, inflammatory disorder of the immune system that can affect many organs. It is called an autoimmune disease because the patient's lymphocytes (white blood cells that normally protect against invading organisms), go out of control and attack the body's own tissues.

Patients between 15 and 40 years of age with severe SLE affecting a major organ that is resistant to standard treatment may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, skin tuberculin test, and radiology studies to evaluate the extent of disease. They have endocrinology, nutrition, dental, and social work consultations, ultrasound or MUGA (multi-gated acquisition scan) scan heart imaging, electrocardiogram and lung function tests, bone marrow biopsy, and lymph node aspirate. Depending on which organs are affected, patients may have additional tests, such as lumbar puncture (spinal tap), kidney or lung biopsy, MRI (magnetic resonance imaging) of the brain and spinal cord, and PET (positron emission tomography) scan. They also complete quality of life questionnaires and have disability functional testing and neurocognitive (thinking) assessments.

Participants have a central venous line (plastic tube) inserted into a neck or chest vein for administering stem cells and medicines and for drawing blood. They undergo seven apheresis procedures during the course of the study to collect stem cells for transplant and for research. For apheresis, whole bloo

Detailed Summary:

Background:

  • Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can involve almost any organ and can range in severity from mild to life-threatening. In spite of significant improvements in survival of SLE patients over last 20 years, a small but significant portion of patients still develop progressive therapy-refractory disease that impairs organ function and overall survival.
  • Since 1996, more than 500 patients have been treated worldwide in pilot trials of autologous hematopoietic stem cell transplantation (autoHSCT) for autoimmune diseases, including about 80 patients with SLE.
  • The rationale for autoHSCT in autoimmune disease is to ablate autoreactive immune effectors and allow reconstitution of a new self-tolerant immune system from the

hematopoietic stem cell. Studies have demonstrated acceptable safety and promising short term efficacy of high-dose cyclophosphamide-based (200 mg/kg) autoHSCT for about 60% of patients with advanced refractory SLE and reacquisition of sensitivity to conventional drugs have been demonstrated in many cases. However, these trials were designed to address the primary endpoint of safety and were inadequate for assessing the disease response.

-Numerous questions about the true efficacy of autoHSCT, optimal transplant regimen, patient selection and mechanisms of action remain unaddressed.

Objectives:

  • The primary objective is to assess the rate of continuous relapse-free complete clinical responses at 24 months post-transplant, with statistical power of 84% to detect, if greater than 70
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome: Relapse-free Complete Clinical Response [ Time Frame: 60 months ]

    Complete clinical response is defined as complete clinical response in the target organ and no clinical signs of active lupus as determined by a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of ≤3; prednisone ≤10mg/day at 6 months and ≤5mg/day at 12 months or later.


    Original Primary Outcome:

    Current Secondary Outcome:

    • Number of Participants With Adverse Events [ Time Frame: 18 months ]
      Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
    • Anti-Nuclear Antibody [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      Anti-Nuclear antibody is a well accepted biological clinical laboratory marker of systemic lupus. Range of normal values is 0-0.9 EU.
    • Extractable Nuclear Antigen (ENA) [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      Extractable nuclear antigen is a well accepted biological clinical laboratory marker of systemic lupus. Range of normal values is 0-19.
    • Anti-Double Stranded Deoxyribonucleic Acid (DNA) Antibody [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      Anti-Double stranded deoxyribonucleic acid antibody is a well accepted biological clinical laboratory marker especially specific for systemic lupus. Range of normal values is 0-24 IU.
    • Anti-Smith-Ribonuclear Protein Antibody [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months and 2 years. ]
      Anti-Smith-Ribonuclear protein antibody is a well accepted biological clinical laboratory marker of systemic lupus.Range of normal values is 0-19 EU.
    • White Blood Cells [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      The white blood cell test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 3.4-9.6 K/uL.
    • Absolute Neutrophil Count [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      The absolute neutrophil count test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 1.29-7.5 K/uL.
    • Absolute Lymphocyte Count [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      The absolute lymphocyte count test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 0.45-4.9 K/uL.
    • Platelet Count [ Time Frame: Day -7, day 0, 1 3, and 6 months, 1 year, 18 months, 2 years and 3 years. ]
      The platelet count test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 162-380 K/uL.
    • Cluster of Differentiation 3 (CD3) + Cells [ Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years. ]
      The CD3+Cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 650-2108 uL.
    • Cluster of Differentiation 4 (CD4) + Cells [ Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years. ]
      The CD4 + Cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 358-1259 uL.
    • Cluster of Differentiation 8 (CD8) + Cells [ Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years. ]
      The CD8 + Cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 194-836 u/L.
    • Cluster of Differentiation 19 (CD19) + Cells [ Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years. ]
      The CD19 + Cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 47-409 u/L.
    • Natural Killer Cells [ Time Frame: Day 0, 1 month, 3 months, 6 months, 1 year and 2 years. ]
      The natural killer cells test was performed to investigate immunological efficacy and mechanisms of response after lymphodepleting auto-hematopoietic stem cell transplant for systemic lupus erythematosus. Range of normal values is 87-505 uL.
    • Syste

      Original Secondary Outcome:

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: February 2, 2004
      Date Started: January 30, 2004
      Date Completion:
      Last Updated: April 9, 2017
      Last Verified: April 2017