RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of R115777 in treating patients who have relapsed or refractory multiple myeloma.

Condition	Treatment or Intervention	Phase
stage II multiple myeloma stage III multiple myeloma refractory plasma cell neoplasm	Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Drug: R115777	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the objective response rate and disease-stabilization rate in patients with relapsed or refractory multiple myeloma treated with R115777. II. Determine whether the degree of inhibition of FTase activity and farnesylation of lamin-B, H-RAS, K-RAS, and N-RAS in peripheral blood mononuclear cells (PBMC) and tumor tissue correlates with tumor response in patients treated with this drug. III. Determine whether the presence of activating RAS mutations in myeloma cells correlates with disease response in patients treated with this drug. IV. Correlate R115777 plasma levels, degree of farnesylation inhibition in PBMC and tumor tissue, and RAS mutation status with tumor response in patients treated with this drug.

PROTOCOL OUTLINE: This is a multicenter study. Patients receive oral R115777 twice daily on days 1-21. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 4 weeks.

PROJECTED ACCRUAL: A total of 12-42 patients will be accrued for this study within 8-25 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-

• Diagnosis of relapsed or refractory multiple myeloma; Bone marrow plasmacytosis with at least 10% plasma cells, sheets of plasma cells, or biopsy-proven plasmacytoma; Myeloma (M)-protein in serum or urine Stage IIA or IIIA
• Previously treated with conventional chemotherapy
• Measurable disease; Serum M-protein component at least 1.0 g/dL OR Urine M-protein excretion greater than 200 mg/24 hours (the following are not considered measurable disease: Lytic bone lesions; Anemia; Bone marrow plasmacytosis; Beta-2 microglobulin in serum)

--Prior/Concurrent Therapy--

• Biologic therapy: At least 2 weeks since prior immunologic agents; Prior thalidomide allowed; No concurrent immunotherapy
• Chemotherapy: See Disease Characteristics; At least 3 weeks since prior cytotoxic chemotherapy; No other concurrent cytotoxic therapy
• Endocrine therapy: At least 2 weeks since prior high-dose corticosteroids; No concurrent corticosteroids; No concurrent hormonal therapy
• Radiotherapy: At least 3 weeks since prior radiotherapy; No concurrent radiotherapy
• Surgery: Not specified
• Other: Concurrent pamidronate or other bisphosphonates allowed; No concurrent anticancer therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-3
• Life expectancy: More than 8 weeks
• Hematopoietic: Absolute neutrophil count at least 1,000/mm3
• Hepatic: Bilirubin no greater than 2 mg/dL; AST or ALT no greater than 2 times upper limit of normal (ULN)
• Renal: Creatinine no greater than 1.5 times ULN; Calcium no greater than 12 mg/dL
• Other: Capable of swallowing intact tablets; No other life-threatening illness unrelated to tumor; No concurrent serious infection; No other active or invasive malignancy within the past 3 years except nonmelanoma skin cancer; No peripheral neuropathy grade 3 or greater; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use 2 forms of effective contraception

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States

Study chairs or principal investigators

Melissa Alsina,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000068759; MCC-12516; MCC-IRB-6028
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00021203
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08