O6-benzylguanine And Carmustine in Treating Patients With Multiple Myeloma

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Treatments

Drug: carmustine

Drug: O6-benzylguanine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00004072

U01CA062502 (U.S. NIH Grant/Contract)

NCI-T97-0021

P30CA043703 (U.S. NIH Grant/Contract)

CWRU-1A96 (Other Identifier)

CWRU1A96

Details and patient eligibility

About

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.

Full description

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.

Enrollment

17 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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: