Clinical trial NCT00002878 (phase 3, status: completed)
Conditions: multiple myeloma and plasma cell neoplasm
ICD codes: C96.20, C96.29, D47.09
Drugs: dexamethasone, doxorubicin hydrochloride, valspodar, vincristine sulfate
SMILES: C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O, C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@@H](NC1=O)C(C)C)C(C)C, CC[C@]1(O)C[C@@H]2CN(C1)CCC1=C(NC3=CC=CC=C13)[C@@](C2)(C(=O)OC)C1=C(OC)C=C2N(C=O)[C@@H]3[C@]4(CCN5CC=C[C@](CC)([C@@H]45)[C@@H](OC(C)=O)[C@]3(O)C(=O)OC)C2=C1
Eligibility 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