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Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

Not Applicable
Completed
Conditions
Lupus Nephritis
Interventions
Procedure: Autologous hematopoietic stem cell transplantation
Registration Number
NCT03828071
Lead Sponsor
Nanjing University School of Medicine
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
stem cell transplantationAutologous hematopoietic stem cell transplantationpatients enrolled in this study will received autologous hematopoietic stem cell transplantation as the initial treatment.
Primary Outcome Measures
NameTimeMethod
Renal remission rateseven years

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

Secondary Outcome Measures
NameTimeMethod
renal survivalseven years

the time from treatment start to dialysis.

treatment related mortality3 months

patients who dies in 3 months after treatment start.

Trial Locations

Locations (1)

National Clinical Research Center of Kidney Diseases, Jinling Hospital

🇨🇳

Nanjing, Jiangsu, China

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