Dexamethasone and Chemotherapy With or Without Plasma Exchange in Patients With Newly Diagnosed Multiple Myeloma and Acute Kidney Failure

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

A Randomised Controlled Trial of Adjunctive Plasma Exchange in Patients With Newly Diagnosed Multiple Myeloma and Acute Renal Failure [MERIT] MyEloma Renal Impairment Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00416897
• Other study ID #: CDR0000523378
• Secondary ID: CRUK-MERITEU-206
• Status: Completed
• Phase: Phase 3
• First received: December 27, 2006
• Last updated: August 23, 2013
• Start date: March 2003
• Est. completion date: December 2008

Study information

• Verified date: June 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Dexamethasone is used to treat multiple myeloma. Drugs used in chemotherapy may stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Plasma exchange is a process in which certain cells are separated from the plasma in the blood by a machine and then only the cells are returned to the patient. Dexamethasone and plasma exchange may be an effective treatment for acute kidney failure caused by multiple myeloma. It is not yet known whether giving dexamethasone and chemotherapy together with plasma exchange is more effective than giving dexamethasone and chemotherapy alone in treating patients with multiple myeloma and acute kidney failure.

PURPOSE: This randomized phase III trial is studying dexamethasone, chemotherapy, and plasma exchange to see how well they work compared with dexamethasone and chemotherapy alone in treating patients with newly diagnosed multiple myeloma and acute kidney failure.

Description:

OBJECTIVES:

Primary

• Compare the effect of dexamethasone and cytotoxic chemotherapy with vs without plasma exchange on the likelihood of renal recovery (i.e., dialysis-independent at 100 days) in patients with newly diagnosed multiple myeloma and acute renal failure.

Secondary

• Compare the overall survival of patients treated with these regimens.

• Compare the quality of life of patients treated with these regimens.

• Determine the value of renal histology in predicting recovery of renal function in these patients.

• Determine the value of serum free light chain assay in determining disease response and renal function recovery in these patients.

OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to planned chemotherapy (vincristine and doxorubicin hydrochloride (VA) or VA-like chemotherapy vs thalidomide-containing chemotherapy vs alkylating agent vs other), frequency of chemotherapy courses (1-3 weekly vs 4 weekly), need for dialysis at randomization (yes vs no), and age (< 65 years vs ≥ 65 years). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral dexamethasone, at least twice daily, on days 1-4 and 9-12. Patients undergo plasma exchange by cytocentrifugation or plasmafiltration over 2-3 hours in weeks 1 and 2 (7 treatments total; 4 of them in week 1). Patients then receive planned chemotherapy per local clinician on days 17-100. Chemotherapy may continue after 100 days at the discretion of the local clinician.

• Arm II: Patients receive dexamethasone and planned chemotherapy as in arm I. Quality of life is assessed at baseline, day 100, and 6 and 12 months.

After completion of study treatment, patients are followed at 6 and 12 months and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma (MM), meeting = 2 of the following criteria:

• Serum or urine* paraprotein

• Bone marrow showing > 10% plasma cells

• Lytic bone lesions NOTE: *The presence of typical myeloma kidney on renal biopsy is considered equivalent to the demonstration of urine paraprotein by electrophoresis

• Acute renal failure attributable to MM, meeting both of the following criteria:

• Creatinine > 5.65 mg/dL OR urine output < 400 mL/day OR requires dialysis

• Unresponsive to treatment with fluids and/or treatment of hypercalcemia with bisphosphonates

• No significant intrinsic renal disease unrelated to MM

PATIENT CHARACTERISTICS:

• Platelet count = 50,000/mm³

• Bilirubin = 1.5 times upper limit of normal (ULN)

• ALT and AST = 2.5 times ULN

• No contraindications to study medication, including the following:

• Active or recent peptic ulcer

• Known significant cardiac insufficiency

• Allergy to study medications

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No known HIV positivity

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for MM

• Prior steroid therapy of = 3 days duration for MM allowed

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma
• Renal Failure
• Renal Insufficiency

Intervention

Drug:
• chemotherapy

• dexamethasone

Procedure:
• plasmapheresis

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Monklands General Hospital	Airdrie	Scotland
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Good Hope Hospital	Birmingham	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Bradford Royal Infirmary	Bradford	England
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	St. Helier Hospital	Carshalton	England
United Kingdom	Saint Richards Hospital	Chichester	England
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Dumfries & Galloway Royal Infirmary	Dumfries	Scotland
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Royal Infirmary - Castle	Glasgow	Scotland
United Kingdom	Harrogate District Hospital	Harrogate	England
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Hull Royal Infirmary	Hull	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester General Hospital	Leicester	England
United Kingdom	Aintree University Hospital	Liverpool	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. Georges, University of London	London	England
United Kingdom	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Hope Hospital	Salford	England
United Kingdom	Staffordshire General Hospital	Stafford	England
United Kingdom	Sunderland Royal Hospital	Sunderland	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	Morriston Hospital NHS Trust	West Glamorgen	Scotland
United Kingdom	New Cross Hospital	Wolverhampton	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales
United Kingdom	Cancer Care Centre at York Hospital	York	England

Sponsors (1)

Lead Sponsor	Collaborator
University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients alive and dialysis-independent at 100 days			No
Secondary	Proportion of patients alive and dialysis-independent at 6 and 12 months			No
Secondary	Overall survival			No
Secondary	Glomerular filtration rate (calculated or measured) at 15 and 100 days and at 6 and 12 months			No
Secondary	Change in serum free light chain levels between days 0 and 15			No
Secondary	Response of myeloma to treatment at 100 days and at 6 and 12 months			No
Secondary	Quality of life			No