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Completed

NCT Number: NCT03828071

Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

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.

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Key information

Age range

14 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

National Clinical Research Center of Kidney Diseases, Jinling Hospital

Nanjing, Jiangsu, 210002, China

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

autologous hematopoietic stem cell transplantation

Procedure

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.

Primary outcomes

  1. Renal remission rate

    Time frame: seven 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 outcomes

  1. renal survival

    Time frame: seven years

    the time from treatment start to dialysis.

  2. treatment related mortality

    Time frame: 3 months

    patients who dies in 3 months after treatment start.

Sponsors and collaborators

Lead sponsor

Nanjing University School of Medicine

Other

Registry information

Official study title

National Clinical Research Center of Kidney Diseases, Jinling Hospital

Important dates

Study start
2011
Primary completion
2015
Study completion
2018
First posted
Feb 4, 2019
Registry last updated
Feb 4, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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