Clinical trial NCT00416897: Dexamethasone and Chemotherapy With or Without Plasma Exchange in Patients With Newly Diagnosed Multiple Myeloma and Acute Kidney Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Renal Failure
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
renal failure
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-12-28
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients alive and dialysis-independent at 100 days
Secondary outcomes:
measure: Proportion of patients alive and dialysis-independent at 6 and 12 months
measure: Overall survival
measure: Glomerular filtration rate (calculated or measured) at 15 and 100 days and at 6 and 12 months
measure: Change in serum free light chain levels between days 0 and 15
measure: Response of myeloma to treatment at 100 days and at 6 and 12 months
measure: Quality of life
Other outcomes:
Locations:
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Birmingham
country: United Kingdom
facility: Good Hope Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Carshalton
country: United Kingdom
facility: St. Helier Hospital
state: England
city: Chichester
country: United Kingdom
facility: Saint Richards Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: St. Georges, University of London
state: England
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals NHS Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Salford
country: United Kingdom
facility: Hope Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: York
country: United Kingdom
facility: Cancer Care Centre at York Hospital
state: England
city: Belfast
country: United Kingdom
facility: Centre for Cancer Research and Cell Biology at Queen's University Belfast
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Airdrie
country: United Kingdom
facility: Monklands General Hospital
state: Scotland
city: Dumfries
country: United Kingdom
facility: Dumfries & Galloway Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Infirmary - Castle
state: Scotland
city: West Glamorgen
country: United Kingdom
facility: Morriston Hospital NHS Trust
state: Scotland
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
state: Wales
Study officials:
affiliation: Hammersmith Hospitals NHS Trust
name: Gill Gaskin, MD
role: STUDY_CHAIR
References: