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