Studies in Patients With Multiple Myelo… | Clinical Trial

Key information

Conditions

Chronic Renal Failure With Uremic Nephropathy

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hôpital Saint Louis

Paris, 75010, France

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

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.

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.

HCO group

Device

TheraliteTM dialyzer of 2.1 m2 in surface

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.

Primary outcomes

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
- 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 outcomes

Improvement in renal function

Time frame: after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year
- DFG (modified MDRD)
- hemodialysis requirement
Hematological response

Time frame: 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)

Time frame: 4 years

Time to progression, relapse or death from randomization
Time to treatment Failure (TTF)

Time frame: 4 years

Time from randomization to progression, relapse, non scheduled hematological treatment or death
Overall survival (OS)

Time frame: 4 years

Time to death from randomization

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study 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.

Acronym: MYRE

Important dates

Study start: 2011
Primary completion: 2015
Study completion: 2017
First posted: Sep 24, 2010
Registry last updated: Dec 8, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.