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

This study is currently recruiting participants.
Verified November 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01208818
First received: September 23, 2010
Last updated: November 19, 2012
Last verified: November 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Chronic Renal Failure With Uremic Nephropathy
 Drug: Cyclophosphamide + Bortezomib + Dexamethasone regimen
Drug: Bortezomib +Dexamethasone regimen
Device: HCO group
Device: conventional high-flux dialyzer
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    • 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 Outcome Measures:
  • Improvement in renal function [ Time Frame: after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year ] [ Designated as safety issue: No ]
    • DFG (modified MDRD)
    • hemodialysis requirement

  • Hematological response [ Time Frame: after 1 and 3 courses, at the end of chemotherapy and at 1 year ] [ Designated as safety issue: No ]
    Partial Response (PR) Very Good Partial Response (VGPR) Complete Response (CR)

  • Progression free survival (PFS) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Time to progression, relapse or death from randomization

  • Time to treatment Failure (TTF) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Time from randomization to progression, relapse, non scheduled hematological treatment or death

  • Overall survival (OS) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Time to death from randomization


Estimated Enrollment: 284
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: BD 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.
Other Name: Bortezomib +Dexamethasone regimen
Experimental: C-BD Drug: 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.
Other Name: Cyclophosphamide + Bortezomib + Dexamethasone regimen
Experimental: HCO 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.
Other Name: Bortezomib +Dexamethasone regimen
Device: HCO group
TheraliteTM dialyzer of 2.1 m2 in surface
Other Name: HCO group
Active Comparator: Control HD 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.
Other Name: Bortezomib +Dexamethasone regimen
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.
Other Name: conventional high-flux dialyzer

Detailed 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01208818

Contacts
Contact: Jean Paul Fermand, MD 33(0)1 42 49 95 48 jpfermand@yahoo.fr

Locations
France
Hôpital Saint Louis Recruiting
Paris, France, 75010
Contact: Jean-Paul Fermand, MD     33(0)1 42499548     jpfermand@yahoo.fr    
Principal Investigator: Jean-Paul Fermand, MD            
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jean-Paul Fermand, MD Hôpital saint Louis, Paris, France
Study Director: Franck Bridoux, MD, PhD CHU Poitiers
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01208818     History of Changes
Other Study ID Numbers: P081226
Study First Received: September 23, 2010
Last Updated: November 19, 2012
Health Authority: France: Ministry of Health

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
Cyclophosphamide
Bortezomib
Dexamethasone
Immunoglobulin Light Chains
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on May 23, 2013