Studies in Patients With Multiple Myeloma and Renal Failure Due to Myeloma Cast Nephropathy
- Conditions
- Chronic Renal Failure With Uremic Nephropathy
- Interventions
- Device: HCO groupDevice: conventional high-flux dialyzer
- Registration Number
- NCT01208818
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 284
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BD Bortezomib +Dexamethasone regimen - HCO Bortezomib +Dexamethasone regimen - HCO HCO group - C-BD Cyclophosphamide + Bortezomib + Dexamethasone regimen - Control HD Bortezomib +Dexamethasone regimen - Control HD conventional high-flux dialyzer -
- Primary Outcome Measures
Name Time Method 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) 3 months after randomization * renal response is defined by creatinine≤ 170 µmol/l and/or DFG (modified MDRD) ≥ 40 ml/min/1.73m2
* the absence of any dialysis requirement will be defined by an eDFG \> 15 ml/min/1.73 m2, 15 days after the last hemodialysis session
- Secondary Outcome Measures
Name Time Method Overall survival (OS) 4 years Time to death from randomization
Hematological response after 1 and 3 courses, at the end of chemotherapy and at 1 year Partial Response (PR) Very Good Partial Response (VGPR) Complete Response (CR)
Improvement in renal function after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year * DFG (modified MDRD)
* hemodialysis requirementTime to treatment Failure (TTF) 4 years Time from randomization to progression, relapse, non scheduled hematological treatment or death
Progression free survival (PFS) 4 years Time to progression, relapse or death from randomization
Trial Locations
- Locations (1)
Hôpital Saint Louis
🇫🇷Paris, France