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

You may be eligible if

• 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