Studies in Patients With Multiple Myeloma and Renal Failure Due to Myeloma Cast Nephropathy (MYRE)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Chronic Renal Failure With Uremic Nephropathy

Treatments: Drug: Bortezomib +Dexamethasone regimen; Device: HCO group; Drug: Cyclophosphamide + Bortezomib + Dexamethasone regimen; Device: conventional high-flux dialyzer

Study type: Interventional

Funder types: Other

Identifiers

NCT01208818

P081226

Details and patient eligibility

About

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.

Full 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).

Enrollment: 284 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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284 participants in 4 patient groups

BD

Active Comparator group

Treatment:

Drug: Bortezomib +Dexamethasone regimen

C-BD

Experimental group

Treatment:

Drug: Cyclophosphamide + Bortezomib + Dexamethasone regimen

HCO

Experimental group

Treatment:

Drug: Bortezomib +Dexamethasone regimen

Device: HCO group

Control HD

Active Comparator group

Treatment:

Device: conventional high-flux dialyzer

Drug: Bortezomib +Dexamethasone regimen