O6-benzylguanine And Carmustine in Treating Patients With 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.

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