Overview

This trial is active, not recruiting.

Condition chronic renal failure with uremic nephropathy
Treatments cyclophosphamide + bortezomib + dexamethasone regimen, bortezomib +dexamethasone regimen, hco group, conventional high-flux dialyzer
Phase phase 3
Sponsor Assistance Publique - Hôpitaux de Paris
Start date June 2011
End date September 2015
Trial size 284 participants
Trial identifier NCT01208818, P081226

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
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. The regimen is given for 3 cycles in the absence of serious side-effect.
(Experimental)
cyclophosphamide + 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.
(Experimental)
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. The regimen is given for 3 cycles in the absence of serious side-effect.
hco group
TheraliteTM dialyzer of 2.1 m2 in surface
(Active Comparator)
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. The regimen is given for 3 cycles in the absence of serious side-effect.
conventional high-flux dialyzer
conventional high-flux dialyzer; polyacrylonitrile, polysulfone, or PMMA dialysers, with an ultrafiltration coefficient > 14 ml/min and ≥ 1.8 m2 in surface, are recommended.

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)
time frame: 3 months after randomization

Secondary Outcomes

Measure
Improvement in renal function
time frame: after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year
Hematological response
time frame: after 1 and 3 courses, at the end of chemotherapy and at 1 year
Progression free survival (PFS)
time frame: 4 years
Time to treatment Failure (TTF)
time frame: 4 years
Overall survival (OS)
time frame: 4 years

Eligibility Criteria

Male or female participants at least 18 years old.

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)

Additional Information

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.
Principal investigator Jean-Paul Fermand, MD
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).
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.