Chronic Renal Failure With Uremic Nephropathy
Conditions
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).
Interventions
DRUGCyclophosphamide + Bortezomib + Dexamethasone regimen
Dosing regimen (21 day-cycle): * Bortezomib 1.3 mg/m2 I.V. on days 1, 4, 8, and 11. An interval of at least 72 hours between each administration of bortezomib is required. * Dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12. * Cyclophosphamide 900 mg/m2 on day 1, through a short I.V. infusion The regimen is given for 3 cycles in the absence of serious side-effect.
DRUGBortezomib +Dexamethasone regimen
Dosing regimen (21 day-cycle): * Bortezomib 1.3 mg/m2 I.V. on days 1, 4, 8, and 11. An interval of at least 72 hours between each administration of bortezomib is required. * Dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12. The regimen is given for 3 cycles in the absence of serious side-effect.
DEVICEHCO group
TheraliteTM dialyzer of 2.1 m2 in surface
conventional high-flux dialyzer; polyacrylonitrile, polysulfone, or PMMA dialysers, with an ultrafiltration coefficient \> 14 ml/min and ≥ 1.8 m2 in surface, are recommended.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Improvement in renal function | after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year | * DFG (modified MDRD) * hemodialysis requirement |
| 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) |
| Progression free survival (PFS) | 4 years | Time to progression, relapse or death from randomization |
| Time to treatment Failure (TTF) | 4 years | Time from randomization to progression, relapse, non scheduled hematological treatment or death |
| Overall survival (OS) | 4 years | Time to death from randomization |
Countries
France
Outcome results
None listed