O6-benzylguanine And Carmustine in Treating Patients With Multiple Myeloma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining O6-benzylguanine with carmustine in treating patients who have previously untreated, refractory, or relapsing multiple myeloma.

OBJECTIVES:

* Evaluate the efficacy of O6-benzylguanine combined with carmustine in patients with previously untreated or refractory multiple myeloma.
* Assess the effects of O6-benzylguanine on bone marrow myeloma cells in this patient population.

OUTLINE: Patients receive O6-benzylguanine IV over 60 minutes followed 1 hour later by carmustine IV over 60 minutes. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses beyond attainment of best response (partial or complete response or stable or plateau disease).

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed progressive multiple myeloma, meeting 1 of the following criteria:

  * Previously untreated
  * Primary refractory
  * Relapsing disease
* Major criteria:

  * Plasmacytomas on tissue biopsy
  * Bone marrow plasmacytosis with greater than 30% plasma cells
  * Monoclonal globulin spike on serum electrophoresis

    * Greater than 3.5 g/dL for G peaks or greater than 2.0 g for A peaks
    * Greater than 1.0 g/24 hours of kappa or lambda light chain excretion on urine electrophoresis in the absence of amyloidosis
* Minor criteria:

  * 10%-30% bone marrow plasmacytosis (criterion A)
  * Presence of monoclonal globulin spike but less than the levels under major criteria (criterion B)
  * Lytic bone lesions (criterion C)
  * IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL (criterion D)
* Must meet one of the following:

  * A minimum of 1 major criterion and 1 minor criterion
  * 3 minor criteria, including criteria A and B

PATIENT CHARACTERISTICS:

Age:

* Not specified

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* WBC greater than 3,000/mm\^3
* Platelet count greater than 100,000/mm\^3
* Absolute neutrophil count greater than 1,500/mm\^3
* Hemoglobin greater than 9 g/dL (transfusions allowed)

Hepatic:

* Bilirubin less than 1.5 mg/dL
* AST/ALT less than 2 times normal

Renal:

* Creatinine no greater than 2.0 mg/dL OR
* Creatinine clearance greater than 60 mL/min
* Calcium less than 14 mg/dL

Pulmonary:

* No prior or concurrent active, symptomatic respiratory disease
* Corrected DLCO at least 60% predicted

Other:

* Controlled diabetes mellitus allowed
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No more than 1 prior chemotherapy regimen containing an alkylating agent for multiple myeloma
* At least 4 weeks since prior chemotherapy

Endocrine therapy:

* Prior corticosteroids for multiple myeloma allowed

Radiotherapy:

* No prior pelvic radiotherapy or radiotherapy to more than 25% of bone marrow

Surgery:

* Not specified