Clinical trial NCT01208818: Studies in Patients With Multiple Myeloma and Renal Failure Due to Myeloma Cast Nephropathy
Official title: Treatment of Renal Failure Due to Myeloma Cast Nephropathy: Comparison of Two Different Chemotherapy Regimens and Evaluation of Optimized Removal of Monoclonal Immunoglobulin Light Chains Using a High Permeability Hemodialysis Membrane.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Renal Failure With Uremic Nephropathy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2010-09-24
Enrollment: 284
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: MYRE is a phase III multicentric controlled national clinical trial conducted in patients with multiple myeloma and renal failure related to myeloma cast nephropathy (MCN). Its aims are to assess (1) the efficacy of bortezomib plus dexamethasone (BD), compared with cyclophosphamide, plus bortezomib and dexamethasone (C-BD) in patients with inaugural MCN not requiring hemodialysis; and (2) in patients with inaugural severe renal failure secondary to biopsy-proven MCN and requiring hemodialysis that of an intensive hemodialysis regimen using either a dialyser with very high permeability to proteins (TheraliteTM) or a conventional high-flux dialyser, while receiving chemotherapy with BD.

Detailed description: MYRE is a phase III multicentric controlled national clinical trial conducted in patients with multiple myeloma and renal failure related to myeloma cast nephropathy (MCN). Its aims are to assess (1) the efficacy of bortezomib plus dexamethasone (BD), compared with cyclophosphamide, plus bortezomib and dexamethasone (C-BD) in patients with inaugural MCN not requiring hemodialysis; and (2) in patients with inaugural severe renal failure secondary to biopsy-proven MCN and requiring hemodialysis that of an intensive hemodialysis regimen using either a dialyser with very high permeability to proteins (TheraliteTM) or a conventional high-flux dialyser, while receiving chemotherapy with BD.

Study hypotheses are: (1) in patients not requiring dialysis, based on renal response after 3 cycles as the main endpoint, to show a benefit of 30% in absolute rate from an expected 30% response rate in the control arm; and (2) in patients requiring hemodialysis, using the prevalence of patients free of dialysis after 3 cycles as the main endpoint, to show a benefit of at least 20% from an assumed rate of 50% in the control arm. A total sample size of 284 patients was computed to be enrolled (type I and II error rates at 5 and 20%, respectively).

Eligibility criteria: Inclusion Criteria:

* Age \>=18 years old
* Serum creatinine \> 170µmol/l and/or DFG \< 40 ml/min/1.73 m2
* Myeloma cast nephropathy (MCN)
* Multiple myeloma
* Informed consent
* neutrophils \>= 1 Giga/L and platelets \>= 70 Giga/L

Exclusion Criteria:

* Amylosis
* Chronic renal Failure with eDFG \< 30 ml/min/1.73 m2, unrelated to myeloma
* Peripheral neuropathy
* Contraindications to either corticosteroids or Bortezomib
* Patient refusal
* Known HIV infection
* Concomitant severe disease including neoplasias (except basocellular carcinoma)
* Liver failure, cytolysis, and/or cholestasis
* Fertile women who refuse or cannot use effective contraception; Women pregnant or nursing; Women with positive test pregnancy (test before treatment initiation)

Primary outcomes:
measure: Prevalence of renal response (if dialysis not mandatory at baseline: strata 1); Prevalence of patients free of dialysis (if dialysis required at baseline; strata 2)
timeFrame: 3 months after randomization
Secondary outcomes:
measure: Improvement in renal function
timeFrame: after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year
measure: Hematological response
timeFrame: after 1 and 3 courses, at the end of chemotherapy and at 1 year
measure: Progression free survival (PFS)
timeFrame: 4 years
measure: Time to treatment Failure (TTF)
timeFrame: 4 years
measure: Overall survival (OS)
timeFrame: 4 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Saint Louis
Study officials:
affiliation: Hôpital saint Louis, Paris, France
name: Jean-Paul Fermand, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Poitiers
name: Franck Bridoux, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Bridoux F, Carron PL, Pegourie B, Alamartine E, Augeul-Meunier K, Karras A, Joly B, Peraldi MN, Arnulf B, Vigneau C, Lamy T, Wynckel A, Kolb B, Royer B, Rabot N, Benboubker L, Combe C, Jaccard A, Moulin B, Knebelmann B, Chevret S, Fermand JP; MYRE Study Group. Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence Among Patients With Myeloma Cast Nephropathy: A Randomized Clinical Trial. JAMA. 2017 Dec 5;318(21):2099-2110. doi: 10.1001/jama.2017.17924.