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