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

NCT ID: NCT01208818

Last Updated: 2017-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

284 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2017-12-31

Brief Summary

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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

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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).

Conditions

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Chronic Renal Failure With Uremic Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BD

Group Type ACTIVE_COMPARATOR

Bortezomib +Dexamethasone regimen

Intervention Type 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.

C-BD

Group Type EXPERIMENTAL

Cyclophosphamide + Bortezomib + Dexamethasone regimen

Intervention Type 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.

HCO

Group Type EXPERIMENTAL

Bortezomib +Dexamethasone regimen

Intervention Type 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.

HCO group

Intervention Type DEVICE

TheraliteTM dialyzer of 2.1 m2 in surface

Control HD

Group Type ACTIVE_COMPARATOR

Bortezomib +Dexamethasone regimen

Intervention Type 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.

conventional high-flux dialyzer

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

HCO group

TheraliteTM dialyzer of 2.1 m2 in surface

Intervention Type DEVICE

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.

Intervention Type DEVICE

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Paul Fermand, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital saint Louis, Paris, France

Franck Bridoux, MD, PhD

Role: STUDY_DIRECTOR

CHU Poitiers

Locations

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Hôpital Saint Louis

Paris, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 29209721 (View on PubMed)

Other Identifiers

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P081226

Identifier Type: -

Identifier Source: org_study_id