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

Chronic Renal Failure With Uremic Nephropathy Clinical Trial

— MYRE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01208818
• Other study ID #: P081226
• Status: Completed
• Phase: Phase 3
• First received: September 23, 2010
• Last updated: December 7, 2017
• Start date: June 2011
• Est. completion date: December 2017

Study information

• Verified date: December 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 284
• Est. completion date: December 2017
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Renal Failure With Uremic Nephropathy
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

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.
• 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.

Device:
• HCO group
TheraliteTM dialyzer of 2.1 m2 in surface
• 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.

Locations

Country	Name	City	State
France	Hôpital Saint Louis	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Improvement in renal function	DFG (modified MDRD); hemodialysis requirement	after 1 cycle of chemotherapy, at the end of chemotherapy, at 6 months and 1 year
Secondary	Hematological response	Partial Response (PR) Very Good Partial Response (VGPR) Complete Response (CR)	after 1 and 3 courses, at the end of chemotherapy and at 1 year
Secondary	Progression free survival (PFS)	Time to progression, relapse or death from randomization	4 years
Secondary	Time to treatment Failure (TTF)	Time from randomization to progression, relapse, non scheduled hematological treatment or death	4 years
Secondary	Overall survival (OS)	Time to death from randomization	4 years