Ixazomib Citrate and Dexamethasone in Treating Patients with High Risk Smoldering Multiple Myeloma

Inclusion Criteria

• Patients must have histologically or cytologically confirmed smoldering multiple myeloma confirmed by Department of Pathology, based on the International Myeloma Working Group Criteria
• Serum myeloma protein (M-protein) >= 3 g/dl and/or bone marrow plasma cells >= 10 %
• Absence of anemia attributed to the plasma cell disorder: hemoglobin > 10 g/dl or not more than 2 g/dL below the lower limit of normal * To be determined based on clinical and laboratory assessment by the primary oncologist
• Absence of renal failure attributed to the plasma cell disorder: calculated creatinine clearance (according to Cockcroft-Gault method, Modification of Diet in Renal Disease [MDRD], or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulae) > 30 mL/min (or alternatively based on standard creatinine level criteria of 2 mg/dl) * To be determined based on clinical and laboratory assessment by the primary oncologist
• Absence of hypercalcemia attributed to the plasma cell disorder*: calcium (Ca) < 10.5 mg/dl or =< 2.5 mmol/L * To be determined based on clinical and laboratory assessment by the primary oncologist
• Absence of lytic bone lesion
• Absence of clonal bone marrow plasma cell percentage >= 60%
• Absence of involved: uninvolved serum free light chain ratio >= 100
• Absence > 1 focal lesions on magnetic resonance imaging (MRI) studies
• “High-risk SMM” per Mayo Clinic or Spanish Programa para et Tratamiento de Hemopatias Malignas (PETHEMA) criteria
• Measurable disease within the past 4 weeks defined by any one of the following * Serum monoclonal protein >= 1.0 g/dl * Urine monoclonal protein > 200 mg/24 hour * Serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Ability to give informed consent
• Absolute neutrophil count >= 1.0 K/uL
• Platelets >= 75 K/uL (platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment)
• Hemoglobin >= 10 g/dL (transfusions are not permissible)
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3.0 X institutional upper limit of normal
• Female patients who: * Are postmenopausal for at least 24 months before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)

Exclusion Criteria

• Participation in other clinical trials, including those with other investigational agents not included in this trial and throughout the duration of this trial; within at least 5 half-lives of previous therapy for smoldering myeloma at start of this trial
• Prior therapy for SMM with a proteasome inhibitor
• Patients with a diagnosis of multiple myeloma (MM) per standard International Myeloma Working Group (IMWG) criteria
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Uncontrolled hypertension or diabetes
• Females patients who are lactating or have a positive serum pregnancy test during the screening period
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
• Patient has >= grade 1 peripheral neuropathy with pain on clinical examination during the screening period
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
• Systemic treatment, within 14 days before study enrollment, with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
• Ongoing or active systemic infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis
• Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Psychiatric illness/social situation that would limit compliance with study requirements
• Corrected QT interval (QTc) > 470 milliseconds (msec) on a 12-lead electrocardiography (EKG) obtained during the screening period; if a machine reading is above this value, the EKG should be reviewed by a qualified reader and confirmed on a subsequent EKG
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible effects of prior chemotherapy
• Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements or GI procedure that could interfere with the oral absorption or tolerance of treatment
• Major surgery within 14 days prior to enrollment
• Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
• Central nervous system involvement (based on clinical assessment)
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
• No current anti-myeloma bisphosphonate therapy (however, prior bisphosphonates and/or bisphosphonate therapy due to osteoporosis is allowed)
• Patients with Paget's disease of the bone
• Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not