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

NCT01208818 | Completed Phase 3 DMC

• 1 other identifier: P081226
• Study Type: interventional
• Target: 284
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Renal Failure With Uremic Nephropathy

Outcome Measures

Primary Outcomes (1)

• 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)

  * 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

  3 months after randomization

Secondary Outcomes (5)

• Improvement in renal function

  after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year

• Hematological response

  after 1 and 3 courses, at the end of chemotherapy and at 1 year

• Progression free survival (PFS)

  4 years

• Time to treatment Failure (TTF)

  4 years

• Overall survival (OS)

  4 years

Study Arms (4)

BD

ACTIVE COMPARATOR

Drug: Bortezomib +Dexamethasone regimen

C-BD

EXPERIMENTAL

Drug: Cyclophosphamide + Bortezomib + Dexamethasone regimen

HCO

EXPERIMENTAL

Drug: Bortezomib +Dexamethasone regimen; Device: HCO group

Control HD

ACTIVE COMPARATOR

Drug: Bortezomib +Dexamethasone regimen; Device: conventional high-flux dialyzer

Interventions

Cyclophosphamide + Bortezomib + Dexamethasone regimen DRUG

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.

C-BD

Bortezomib +Dexamethasone regimen DRUG

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.

BD; Control HD; HCO

HCO group DEVICE

TheraliteTM dialyzer of 2.1 m2 in surface

HCO

conventional high-flux dialyzer DEVICE

conventional high-flux dialyzer; polyacrylonitrile, polysulfone, or PMMA dialysers, with an ultrafiltration coefficient \> 14 ml/min and ≥ 1.8 m2 in surface, are recommended.

Control HD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Saint Louis

Paris, 75010, France

Location

Related Publications (1)

• 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.

  PMID: 29209721 DERIVED

MeSH Terms

Interventions

Cyclophosphamide; Bortezomib

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jean-Paul Fermand, MD

  Hôpital saint Louis, Paris, France

  PRINCIPAL INVESTIGATOR

• Franck Bridoux, MD, PhD

  CHU Poitiers

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Study Start: June 1, 2011
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2017
• Last Updated: December 8, 2017

Record last verified: 2017-12

Locations

FR (1)