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

Sponsor

University of Glasgow (Other)

Overall Status

Completed

CT.gov ID

NCT00416897

Collaborator

(none)

280

Enrollment

Locations

69.1

Duration (Months)

7.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm Renal Failure	Drug: chemotherapy Drug: dexamethasone Procedure: plasmapheresis	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2003

Actual Study Completion Date :

Dec 1, 2008

Outcome Measures

Primary Outcome Measures

Proportion of patients alive and dialysis-independent at 100 days []

Secondary Outcome Measures

Proportion of patients alive and dialysis-independent at 6 and 12 months []
Overall survival []
Glomerular filtration rate (calculated or measured) at 15 and 100 days and at 6 and 12 months []
Change in serum free light chain levels between days 0 and 15 []
Response of myeloma to treatment at 100 days and at 6 and 12 months []
Quality of life []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England	United Kingdom	RG24 9NA
2	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England	United Kingdom	B15 2TH
3	Good Hope Hospital	Birmingham	England	United Kingdom	B75 7RR
4	Birmingham Heartlands Hospital	Birmingham	England	United Kingdom	B9 5SS
5	Bradford Royal Infirmary	Bradford	England	United Kingdom	BD9 6RJ
6	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England	United Kingdom	BN2 5BE
7	Bristol Haematology and Oncology Centre	Bristol	England	United Kingdom	BS2 8ED
8	Addenbrooke's Hospital	Cambridge	England	United Kingdom	CB2 2QQ
9	Kent and Canterbury Hospital	Canterbury	England	United Kingdom	CT1 3NG
10	St. Helier Hospital	Carshalton	England	United Kingdom	SM5 1AA
11	Saint Richards Hospital	Chichester	England	United Kingdom	P019 4SE
12	Walsgrave Hospital	Coventry	England	United Kingdom	CV2 2DX
13	Harrogate District Hospital	Harrogate	England	United Kingdom	HG2 7SX
14	Wycombe General Hospital	High Wycombe	England	United Kingdom
15	Hull Royal Infirmary	Hull	England	United Kingdom	HU3 2KZ
16	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
17	Leicester General Hospital	Leicester	England	United Kingdom	LE5 4PW
18	Aintree University Hospital	Liverpool	England	United Kingdom	L9 7AL
19	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
20	St. Georges, University of London	London	England	United Kingdom	SW17 ORE
21	Hammersmith Hospital	London	England	United Kingdom	W12 OHS
22	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England	United Kingdom	NE7 7DN
23	Nottingham City Hospital	Nottingham	England	United Kingdom	NG5 1PB
24	Oxford Radcliffe Hospital	Oxford	England	United Kingdom	0X3 7LJ
25	Hope Hospital	Salford	England	United Kingdom	M6 8HD
26	Staffordshire General Hospital	Stafford	England	United Kingdom	ST16 3SA
27	Sunderland Royal Hospital	Sunderland	England	United Kingdom	SR4 7TP
28	Royal Cornwall Hospital	Truro, Cornwall	England	United Kingdom	TR1 3LJ
29	New Cross Hospital	Wolverhampton	England	United Kingdom	WV10 0QP
30	Cancer Care Centre at York Hospital	York	England	United Kingdom	Y031 8HE
31	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland	United Kingdom	BT9 7BL
32	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
33	Monklands General Hospital	Airdrie	Scotland	United Kingdom	ML6 0JF
34	Dumfries & Galloway Royal Infirmary	Dumfries	Scotland	United Kingdom	DG1 4AP
35	Ninewells Hospital	Dundee	Scotland	United Kingdom	DD1 9SY
36	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU
37	Royal Infirmary - Castle	Glasgow	Scotland	United Kingdom	G4 0SF
38	Morriston Hospital NHS Trust	West Glamorgen	Scotland	United Kingdom	SA6 6NL
39	Wrexham Maelor Hospital	Wrexham	Wales	United Kingdom	LL13 7TD