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

Inclusion Criteria

• •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