Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

National Clinical Research Center of Kidney Diseases, Jinling Hospital

In this study, we aimed to evaluate the long term efficacy, remission, survival and safety of autologous hematopoietic stem cell transplantation in patients with refractory lupus nephritis.

This is an single arm, non-randomized study. Patients who were diagnosed with relapsed and refractory lupus nephritis would included in this study. Refractory lupus nephritis is defined as no response to at least one type of immunosuppressant therapy (including corticosteroids, cyclophosphamide, tacrolimus, mycophenolate mofetil and cyclosporine) for more than six months, or relapse during the period maintenance therapy with kidney pathological transformation or persistently positive antibodies. Close observation was carried out at stem cell harvest, at transplantation, at 3, 6, 12, 18, and 24 months and then once a year after autologous stem cell transplantation.

20-30 cases will be included in this study.

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Procedure: Autologous hematopoietic stem cell transplantation

Detailed Description

Treatment plan: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was administered when the level of peripheral leucocytes was < 1×109/L. Peripheral leukocyte counts were monitored, and harvesting was performed when the peripheral white blood cell level rebounded (usually 11 days after cyclophosphamide). The target acquisition was CD34+ cells > 2×10^6/kg and mononuclear cells > 2×10^8/kg. The graft was preserved at a temperature of -196 ℃ for further use. The conditioning regimen consisted of intravenous cyclophosphamide (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose of cyclophosphamide and ATG could be reduced according to the patients' condition. Methylprednisolone (80-500 mg/day) was administered through intravenous drip at the same time with ATG to reduce anaphylaxis. The incidence of drug-related complications was decreased by hyperhydration (the volume of infusion liquid is 50 ml/kg/day), urine alkalization (infusion of sodium bicarbonate 250ml/day), and anti-emetic medication. G-CSF (0.5 μg/kg/d) was administered to each patient beginning the day after stem cells reinfusion until the level of absolute peripheral neutrophil count was consecutively higher than 1.0 × 10^9/L.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • National Clinical Research Center of Kidney Diseases, Jinling Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Diagnosed with relapsed and refractory lupus nephritis; 2. Ages from 14 - 45 years old; 3. Serum creatinine < 2mg/dl; 4. Alanine aminotransferase < 2 times of normal upper limit; 5. Left ventricular ejection fraction > 50%; 6. Subjects (or their legal representatives) must signed an informed consent document.

Exclusion Criteria:

• 1. Active infection; 2. Known or suspected hypersensitivity to CTX or ATG; 3. Subjects suffering from uncontrolled or severe cardiovascular disease; 4. Subjects suffering from serious physical disease and mental illnesses.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: stem cell transplantation; patients enrolled in this study will received autologous hematopoietic stem cell transplantation as the initial treatment.

Procedure: Autologous hematopoietic stem cell transplantation; Stem cell mobilization and collection: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) for 2 days and granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg per day was administered when the level of peripheral leucocytes was < 1×109/L. Peripheral leukocyte counts were monitored, and harvesting was performed when the peripheral white blood cell level rebounded . Conditioning and reinfusion of stem cells: The conditioning regimen consisted of intravenous cyclophosphamide (40 mg/kg/day × 4 days) 5 days before transplantation (a total dose 160 mg/kg) and rabbit antithymocyte globulin (ATG) (2.5mg/kg/day × 3 days) 4 days before transplantation. The dose of cyclophosphamide and ATG could be reduced according to the patients' condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal remission rate	The curative effect on the kidney was defined as follows: complete remission: proteinuria< 0.4 g/24 h, red blood cell (RBC) < 3/HP in urine sediment, serum albumin > 3.5g/dl and serum creatinine < 1.24 mg/dl; partial remission: 50% baseline < decrease of proteinuria < 3.5 g/24 h, serum albumin >30g/L and serum creatinine < 1.24 mg/dl, no remission (NR): failed to achieve partial remission	seven years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
renal survival	the time from treatment start to dialysis.	seven years
treatment related mortality	patients who dies in 3 months after treatment start.	3 months

Collaborators and Investigators

• Sponsor: Nanjing University School of Medicine
• Investigators: Principal Investigator: zhihong liu, MD, National Clinical Research Center of Kidney Diseases, Jinling Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2011
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): February 4, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: NJCT-1008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No