European Trial of Free Light Chain Removal by Extended Haemodialysis in Cast Nephropathy

Study Overview
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Brief Summary
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Hypothesis: Free light chain removal haemodialysis will increase the rate of renal recovery in patients with cast nephropathy, severe renal failure and de novo multiple myeloma. This study will randomise patients with multiple myeloma and severe renal failure to treatment to remove free light chains by haemodialysis or not.

Detailed Description
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The EUropean trial of free LIght chain removal by exTEnded haemodialysis in cast nephropathy (EuLITE) trial is a prospective, randomised, multicentre, open label clinical trial to investigate the clinical benefit of FLC removal haemodialysis in patients with cast nephropathy, dialysis dependent renal failure and de novo multiple myeloma. Recruitment commenced in May 2008, in total 90 patients will be recruited. Participants will be randomised, centrally, upon enrolment, to either trial chemotherapy and FLC removal haemodialysis or trial chemotherapy and standard high flux haemodialysis. Trial chemotherapy is a modified PAD regime, consisting of bortezomib, doxorubicin and dexamethasone. FLC removal haemodialysis is undertaken using two Gambro HCO 1100 dialysers in series, over an intensive treatment schedule. The primary outcome for the study is independence of dialysis at 3 months. Secondary outcomes are: duration of dialysis, reduction in serum FLC concentrations; myeloma response and survival.

Official Title
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European Trial of Free Light Chain Removal by Extended Haemodialysis in Cast Nephropathy

Conditions
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Multiple Myeloma, Cast Nephropathy, Kidney Failure

Intervention / Treatment
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* Device: FLC removal HD (Gambro HCO 1100)
* Procedure: Standard dialysis on a high flux ployflux dialyser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Dialysis dependent acute renal failure (eGFR <15ml/min/1.73m2) Fulfils diagnostic criteria for the diagnosis of symptomatic de novo multiple myeloma1 Abnormal serum FLC ratio and a sFLC concentration > 500 mg/L Myeloma kidney demonstrated on a renal biopsy (cast nephropathy) Ability to give informed consent to partake in study Commencement of study within 10 days of presenting to enrolling unit Exclusion Criteria: Age < 18 years Known advanced chronic renal failure (CKD stage IV 4-5; eGFR <30mls/min/1.73m2) or evidence of significant chronic damage on renal biopsy Amyloidosis or light chain deposition disease on renal biopsy Previous treatment of multiple myeloma with chemotherapy Haemodynamic instability that precludes unsupported dialysis renal replacement therapy Significant cardiac disease (myocardial infarction with in the last 6 months; unstable angina; NYHA class III or IV heart failure; clinically significant pericardial disease; cardiac amyloidosis) Advanced disease or significant co-morbidity: with poor short term prognosis, necessitating palliation and no active or disease specific treatment. Inability to give informed consent History of allergic reaction attributable to compounds containing boron or mannitol History of Peripheral neuropathy or neuropathic pain (grade 2 or higher as defined by NCI CTCAE version 3) Clinically significant liver dysfunction (bilirubin >1.8mg/dl (30µmol/L)) Known HIV infection Active uncontrolled infection Pregnant and lactating women Inability to give informed consent Pre-menopausal female patients of childbearing potential: positive pregnancy test or unwilling to use effective contraception during the study Lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive FLC removal HD undertaken using an extended dialysis schedule on the Gambro HCO 1100 dialysers | Device: FLC removal HD (Gambro HCO 1100)<br>* FLC removal HD using a extended dialysis schedule on the Gambro HCO 1100<br>* Other names: Gambro HCO 1100;|
| Active Comparator: 2<br>Patients receive standard dialysis on a high flux ployflux dialyser at a frequency determined by the duty nephrologist | Procedure: Standard dialysis on a high flux ployflux dialyser<br>* Standard dialysis on a high flux ployflux dialyser at a frequency determined by the duty nephrologist<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Independence of haemodialysis at 3 months from enrollment (eGFR > 15mls/min/1.73m2 at 2 weeks after last dialysis session) |  | 3 months from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency of extended HD with respect to reduced sFLC concentrations; duration of HD before renal recovery; multiple myeloma response to chemotherapy and suitability for stem cell transplantation; mortality over 24 months observation period |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Multiple myeloma, Cast nephropathy, Kidney failure