Combination Chemotherapy With or Without PSC 833 in Treating Patients With Relapsed or Refractory Multiple Myeloma

DISEASE CHARACTERISTICS: Multiple myeloma of any stage confirmed by: Bone marrow plasmacytosis with at least 10% plasma cells, sheets of plasma cells, or biopsy proven plasmacytosis Myeloma (M) protein in serum and/or urine Measurable disease by at least one of the following: Serum M-component at least 1.0 g/dL by electrophoresis Baseline measurement by nephelometry also, if used to follow response Urine M-protein excretion greater than 200 mg/24 hours by electrophoresis The following are not considered measurable but are followed for response: Lytic bone lesions Bone marrow plasmacytosis Anemia Serum beta 2-microglobulin Objective evidence of progression by at least one of the following: Increased serum M-protein (by electrophoresis unless M-spike less than 1.5 g/dL) At least 50% above lowest remission level or by at least 2 g/dL To more than 1.0 g/dL if sole protein indication of relapse Nephelometry may be used instead of electrophoresis Increased urine M-protein To 50% above lowest level OR by 2 g/24 hours To greater than 200 mg/24 hours Definite new lytic bone lesions or at least a 50% increase in size of existing lesions (discussion with ECOG Study Chairman required if sole indication of progression) Increase in serum or urine M-protein by 25% to under 50% (as above) plus one of the following: Serum calcium greater than 12 mg/dL without other cause Hemoglobin decreased by more than 2.0 g/dL not attributed to chemotherapy, interferon therapy, or a myelodysplastic syndrome Less than 11 g/dL in men Less than 10 g/dL in women At least a 50% increase in bone marrow plasmacytosis Failure of prior cytotoxic therapy defined by one of the following: Never responded Relapsed within 2 months of last treatment Relapsed 2-12 months after last treatment following initial response Adequate prior chemotherapy required, e.g.: At least 2 courses of combination chemotherapy (e.g., VBMCP, VBAP, MP) Prior vincristine, doxorubicin, and dexamethasone (VAD) allowed No demonstrated resistance to VAD At least 3 months since prior VAD Cumulative doxorubicin dose no more than 250 mg/m2 Prior autologous peripheral blood stem cell transplant allowed if performed prior to development of drug resistance No prior allogeneic transplant No smoldering myeloma, localized plasmacytoma, or monoclonal gammopathy of undetermined significance (MGUS) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-3 Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 50,000/mm^3 Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) AST less than 1.5 times ULN No chronic or active hepatitis or cirrhosis Renal: Creatinine less than 3.0 mg/dL Cardiovascular: Ejection fraction at least 50% No history of congestive heart failure No overt angina despite medication No myocardial infarction within 2 months No poorly controlled hypertension (i.e., pressure 200/110 or higher despite medication) No arrhythmia requiring therapy (i.e., sustained atrial or ventricular arrhythmia or multifocal premature ventricular contraction) Digoxin to control ventricular rate of atrial fibrillation that has been chronic for more than 1 month allowed Neurologic: No peripheral neuropathy with weakness No cerebellar disease with ataxia Gastrointestinal: Adequate gastrointestinal function to allow absorption of PSC 833 No active peptic ulcer Other: No hypersensitivity to PSC 833 or cyclosporine No active infection HIV negative No uncontrolled diabetes mellitus No second malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other localized cancer treated with surgery alone Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other serious medical problem unless sufficiently stabilized PRIOR CONCURRENT THERAPY: Biologic therapy: Prior biologic therapy (e.g., interferon) allowed Chemotherapy: See Disease Characteristics At least 3 weeks since other prior chemotherapy (including plicamycin) Endocrine therapy: At least 2 weeks since high dose steroids (at least 100 mg/m2/day of prednisone or at least 40 mg/day of dexamethasone (including steroids for hypercalcemia) Radiotherapy: At least 2 weeks since prior radiotherapy except limited radiotherapy to a single bone lesion Surgery: At least 4 weeks since prior major surgery Other: No concurrent anticoagulants No concurrent drugs known to modulate cyclosporine blood concentrations