O6-benzylguanine And Carmustine in Treating Patients With Multiple Myeloma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Trial of O6-Benzylguanine (NSC 637037) and BCNU in Patients With Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: O6-benzylguanine
* Drug: carmustine


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: O6-benzylguanine|Patients receive O6-benzylguanine 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.|
|Drug: carmustine|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of O6-benzylguanine combined with carmustine in patients with previously untreated or refractory multiple myeloma. |  | Every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses beyond attainment of best response. Patients are followed every 2 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma