Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG)/Rituximab in Patients With Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is designed to examine whether treating patients with lupus with high dose
      cyclophosphamide together with rATG/rituximab (drugs which reduce the function of the immune
      system), followed by return of their previously collected stem cells will result in
      improvement in the disease. Stem cells are undeveloped cells that have the capacity to grow
      into mature blood cells, which normally circulate in the blood stream. The purpose of the
      intense chemotherapy is to destroy the cells in the immune system which may be causing this
      disease. The purpose of the stem cell infusion is to produce a normal immune system that will
      no longer attack body. The study purpose is to examine whether this treatment will result in
      improvement in the lupus disease.
    

Detailed description: 
      Mobilization Participants will be administered Cyclophosphamide at 2.0 g/m2 in 200 ml of
      normal saline (NS) over 1 hour. Hydration with 0.9 NS at approximately 100-250-ml/ hour will
      begin 4 hours prior to cyclophosphamide and continued for 24 hours after termination of
      cyclophosphamide. Urine output approximately greater than 100 ml/hour should be maintained.

      Granulocyte-colony stimulating factor (G-CSF) will be administered subcutaneously at 5-10
      mcg/kg/day and will be started 5 days after termination of cyclophosphamide administration.

      After the absolute neutrophil count is greater than 1000/ul or after hematological nadir,
      leukapheresis using a continuous flow blood cell separator will be initiated. A 10-15 liter
      apheresis will be performed unless stopped earlier for clinical judgment of toxicity (e.g.,
      numbness, tetany). The G-CSF will continue until apheresis is discontinued. If necessary,
      platelets will be transfused to greater than 60,000/ul prior to each apheresis.

      Conditioning Regimen Mesna: 50mg/kg/day x 4 days will be given intravenously over 24 hours.

      Cyclophosphamide: 50 mg/kg/day x 4 days (the lesser of ideal or actual weight) will be given
      intravenously over 1 hour in 250 cc of normal saline on days -5 through -2.

      Hydration: approximately 50-200cc/hour in adults should begin 6 hours before cyclophosphamide
      and continue until 24 hours after the last cyclophosphamide dose. Hydration rates need to be
      individually adjusted by daily weights to maintain dry weight count. Twice daily weights will
      be obtained. Warning: Participants with renal insufficiency are prone to volume overload.
      Early institution of ultrafiltration or dialysis is recommended.

      rATG 0.5mg/kg will be given IV on day -5, 1.0mg/kg will be given on day

      -4, 1.5mg/kg will be given IV on days -3, -2, -1 (no dose adjustment). It will be given over
      10 hours. Premedicate with Solumedrol 250mg IV, acetaminophen 650mg po qd and diphenhydramine
      25mg 30 minutes before infusion.

      Rituximab 500mg/day will be given IV on days -6 and +1. At the first dose (D-6), rituximab
      infusion will be started at 50mg/h and escalate the infusion rate by 50mg every 30minutes to
      a maximum of 400mg/h. Starting the second dose (days -4, -2 and +1). IV infusion will be
      started at 100mg/h and escalate the infusion rate 100mg every 30minutes to a maximum of
      400mg/h. Premedicate with Solumedrol 250mg IV, acetaminophen 650mg po qd and diphenhydramine
      25mg 30 minutes before infusion on days -6 and +1. Premedicate acetaminophen 650mg po qd and
      diphenhydramine 25mg 30 minutes before infusion on days -4 and -2.

      Stem Cell Reinfusion Previously collected stem cells will be reinfused on day 0 as noted in
      Table 4. The stem cells are infused over approximately 20 minutes through the central venous
      catheter, such as a peripherally inserted central catheter (PICC line). Following stem cell
      reinfusion, routine daily labs will be obtained including complete blood count (CBC),
      chemistry panel, and liver function tests. Antibiotics and blood transfusions will be
      administered as required by clinical judgment.
    

Intervention name(s): Hematopoietic stem cell transplantation
Intervention type(s): Biological
Intervention description(s): Autologous hematopoietic stem cell transplantation
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stem cell, Autoimmune disease, Systemic Lupus Erythematosus