Clinical Drug Experience Knowledgebase

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