Tipifarnib and Bortezomib in Treating Patients With Relapsed Multiple Myeloma

Inclusion Criteria: * Diagnosis of multiple myeloma * Stage II or III disease * Relapsed disease after ≥ 2 prior therapies\*, confirmed by the presence of 1 of the following: * New lytic lesion * A 25% increase in urine or serum monoclonal protein * Patients who received prior bortezomib must have responded to therapy * Measurable disease, defined by 1 or more of the following criteria: * Serum M-component ≥ 1.0 g/dL by serum protein electrophoresis * Urine M-protein excretion \> 200 mg per 24-hour collection, by urine protein electrophoresis * Performance status - Karnofsky 60-100% * More than 8 weeks * Platelet count ≥ 100,000/mm\^3 * Absolute neutrophil count ≥ 1,000/mm\^3 * Bilirubin ≤ 2 mg/dL * Direct bilirubin ≤ 2 times upper limit of normal (ULN) * AST or ALT ≤ 2 times ULN * Creatinine ≤ 1.5 times ULN * Calcium ≤ 12 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow study medication * Capable of following directions regarding study medication, or has a daily caregiver who will be responsible for administering study medication * No peripheral neuropathy ≥ grade 2 * No hypersensitivity to any of the following: * Bortezomib * Boron * Mannitol * Imidazole compounds (e.g., clotrimazole, ketoconazole, miconazole, econazole) * No serious medical or psychiatric illness that would preclude study compliance * No other life-threatening illness (unrelated to tumor) * No other active or invasive malignancy within the past 3 years except for nonmelanoma skin cancer * No serious infection * No prior allogeneic bone marrow transplantation * More than 30 days since prior and no concurrent immunotherapy * More than 30 days since prior and no concurrent cytotoxic chemotherapy * More than 14 days since prior high-dose corticosteroids * No concurrent therapeutic corticosteroids (e.g., \> 10 mg prednisone per day) * No concurrent hormonal therapy * No concurrent antiemetic corticosteroids * More than 14 days since prior and no concurrent radiotherapy * More than 1 year since prior bortezomib * More than 14 days since prior investigational drugs * No prior tipifarnib * No other concurrent cancer-related treatment * No concurrent administration of the following enzyme-inducing anti-epileptic drugs: * Phenytoin * Phenobarbital * Carbamazepine * No concurrent magnesium- or aluminum-based antacids within 2 hours before or after tipifarnib administration * Concurrent pamidronate or other bisphosphonates allowed