Cyclophosphamide and rATG/Rituximab in Patients With Systemic Lupus Erythematosus
|Systemic Lupus Erythematosus||Biological: Hematopoietic stem cell transplantation||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Cyclophosphamide and rATG/Rituximab in Patients With Systemic Lupus Erythematosus: Phase II Trial|
- The primary efficacy outcome is overall survival and the proportion of participants who achieve and maintain remission after transplant. [ Time Frame: 5 years after transplant ]
|Study Start Date:||August 2005|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation will be performed
Biological: Hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
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.
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. BID weights will be obtained. Warning: Participants with renal insufficiency are prone to volume overload. Early institution of ultrafiltration or dialysis is recommended.
Rabbit ATG 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 (e.g., PICC line). Following stem cell reinfusion, routine daily labs will be obtained including CBC, chemistry panel, and liver function tests. Antibiotics and blood transfusions will be administered as required by clinical judgment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00278538
|United States, Illinois|
|Northwestern University, Feinberg School of Medicine|
|Chicago, Illinois, United States, 60611|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||Richard Burt, MD||Northwestern University|