Clinical trial NCT00700531: European Trial of Free Light Chain Removal by Extended Haemodialysis in Cast Nephropathy
Official title: European Trial of Free Light Chain Removal by Extended Haemodialysis in Cast Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Myeloma
Cast Nephropathy
Kidney Failure
Keywords: Hemodialysis
Multiple myeloma
Cast nephropathy
Kidney failure
Lead sponsor: University Hospital Birmingham
Sponsor class: OTHER
Collaborators: name: Gambro Renal Products, Inc.
name: Ortho Biotech, Inc.
First posted: 2008-06-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Independence of haemodialysis at 3 months from enrollment (eGFR > 15mls/min/1.73m2 at 2 weeks after last dialysis session)
timeFrame: 3 months from enrollment
Secondary outcomes:
measure: 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
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham
state: West Midlands
Study officials:
affiliation: University Hospital Birmingham
name: Paul Cockwell, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Birmingham
name: Mark Cook, PhD FRCPath
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, Hattersley J, Evans ND, Chappell MJ, Cook M, Goehl H, Storr M, Bradwell AR. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol. 2007 Mar;18(3):886-95. doi: 10.1681/ASN.2006080821. Epub 2007 Jan 17.
citation: Hutchison CA, Harding S, Mead G, Goehl H, Storr M, Bradwell A, Cockwell P. Serum free-light chain removal by high cutoff hemodialysis: optimizing removal and supportive care. Artif Organs. 2008 Dec;32(12):910-7. doi: 10.1111/j.1525-1594.2008.00653.x.
citation: Hutchison CA, Cook M, Heyne N, Weisel K, Billingham L, Bradwell A, Cockwell P. European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): a randomised control trial. Trials. 2008 Sep 28;9:55. doi: 10.1186/1745-6215-9-55.