Protocol of the Combination of Bortezomib and Tipifarnib for Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• •Patients included in the study must meet criteria for relapsed or refractory multiple myeloma. Relapsed myeloma is defined in patients as increasing M-Spike or plasmacytoma compared to a previous measurement confirmed on at least two different settings. Refractory myeloma is defined as progression of disease on current therapy, and having received at least two courses of treatment with or without the use of high dose therapy and autologous transplant.
• •Patients must have received at least 2 prior lines of therapy in order to be eligible for this treatment.
• •Must be ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of bortezomib in combination with tipifarnib in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
• •Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (Karnofsky ≥ 60%, see Appendix A).
• •Life expectancy of greater than 12 weeks.
• •Patients must have organ and marrow function as defined below:
• •* Leukocytes ≥ 1,000/microliter (mcL)
• •* Absolute neutrophil count ≥ 500/mcL
• •* Platelets ≥ 25,000/mcL
• •* Total bilirubin within normal institutional limits
• •* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X institutional upper limit of normal
• •* Creatinine ≤ 2.5 OR
• •* Creatinine clearance ≥ 20 mL/min/1.73 m² for patients with creatinine levels above institutional normal.
• •Eligibility of patients receiving any medications or substances with the potential or known to affect the activity or pharmacokinetics of bortezomib or tipifarnib will be determined following review of their case by the Principal Investigator. Patients must be on bisphosphonates therapy unless precluded by osteonecrosis of the jaw (ONJ) or other clinical circumstances at the investigators discretion. Patients may receive erythroid growth factors as needed, per institutional guidelines. Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs) (e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450 3A4 (CYP3A4) inducer such as rifampin or St. John's wort.
• •The effects of bortezomib and tipifarnib on the developing human fetus are unknown. For this reason, women with child-bearing potential and men must agree to use adequate contraception prior to entering the study. Adequate contraception includes hormonal therapy, a barrier method of birth control or abstinence. Appropriate contraception must be used for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately, and will be immediately discontinued from the study. Any woman who becomes pregnant during the study will be followed throughout their pregnancy until its outcome (i.e. delivery, still birth, miscarriage).
• •* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• •* Male subject agrees to use an acceptable method of contraception for the duration of the study.
• •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• •Both men and women of all races and ethnic groups are eligible for this trial.