Clinical trial NCT03828071: Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis
Official title: National Clinical Research Center of Kidney Diseases, Jinling Hospital
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lupus Nephritis
Lead sponsor: Nanjing University School of Medicine
Sponsor class: OTHER
First posted: 2019-02-04
Enrollment: 22
Sex: ALL
Minimum age (years): 14
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Renal remission rate
timeFrame: seven years
Secondary outcomes:
measure: renal survival
timeFrame: seven years
measure: treatment related mortality
timeFrame: 3 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: National Clinical Research Center of Kidney Diseases, Jinling Hospital
state: Jiangsu
Study officials:
affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital
name: zhihong liu, MD
role: PRINCIPAL_INVESTIGATOR
References: