Velcade for Proliferative Lupus Nephritis

Study Overview
=================
Brief Summary
-----------------
The primary objective is to test the safety and efficacy of Velcade to induce remission in WHO class III/IV/V lupus nephritis that are refractory to standard medications.

Detailed Description
-----------------
This exploratory single center, open-label, single treatment group assignment, safety, and efficacy study will enroll 14 patients with WHO class III/IV/V lupus nephritis. Subjects will receive 12 doses of Velcade to induce clinical remission.

Official Title
-----------------
Velcade for Proliferative Lupus Nephritis

Conditions
-----------------
Lupus Nephritis, Proteinuria, Hematuria

Intervention / Treatment
-----------------
* Drug: Velcade


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ACR criteria for lupus (minimum 4 out of 11). Biopsy proven WHO class III or IV or V lupus nephritis with clinical activity. GFR must be greater or equal to 30 cc/min/1.73 m2. Proteinuria must exceed 1000 mg per day except for WHO class V lupus nephritis, daily proteinuria must be greater or equal to 2000 mg. Primary therapy for active disease must have been given at least 6 months prior to protocol enrollment for WHO lupus III/IV. Exclusion Criteria: Serum creatinine of more than 3.0 mg/dL on repeated testing. Greater than 50% fibrosis on renal biopsy. Platelet count of less than 30× 109/L. Absolute neutrophil count of less than 1.0 × 109/L. Greater than or equal to Grade 1 peripheral neuropathy. Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure. Hypersensitivity to Velcade, boron or mannitol. Serious medical conditions and infections (including HIV, HCV, HBV) or psychiatric illness. Known history of untreated positive PPD. Serious complications from systemic lupus such as cerebral lupus and severe active infections. Diagnosed or treated for another malignancy within 3 years of enrollment. Greater than 1.5x upper limit of normal total bilirubin.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Velcade Therapy<br> | Drug: Velcade<br>* Velcade at 1.3 mg/m2, on days 1, 4, 8 and 11 (=1 cycle). The study will involve 3 cycles of Velcade therapy.<br>* Other names: Proteasome inhibitor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria | Quantification of 24 hr urinary protein. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function | Serum creatinine and GFR | 1 year | 
| Lupus activity score | Assessment of SELENA-SLEDAI | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Proliferative lupus nephritis, WHO class III/IV/V lupus nephritis, Proteinuria, Hematuria, Velcade, SLE, Bortezomib, Proteasome inhibitor