Trial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom's Macroglobulinemia

Inclusion Criteria: * Male or female patients 18 years or older. * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care. * Female patients who: * Are postmenopausal for at least 1 year 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, AND * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) * Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: * 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 (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) * Clinicopathological diagnosis of WM (Owen 2003), with symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM (Kyle 2003), and measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of \>2 times the upper limit of normal. * Eastern Cooperative Oncology Group performance status of 0, 1, or 2. * Patients must meet the following clinical laboratory criteria * Absolute neutrophil count ≥1,000/mm3 and platelet count ≥75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. * Total bilirubin ≤1.5 x the upper limit of the normal range (ULN). * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN. * Calculated creatinine clearance ≥30 mL/min. Exclusion Criteria: * Female patients who are lactating or have a positive serum pregnancy test during the screening period. * Major surgery within 14 days before enrollment. * Central nervous system involvement. * Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. * 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 the first dose, with strong inhibitors of cytochrome P (CYP) 1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort. * Known hepatitis B or C virus, or HIV infection. * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. * Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. * Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. * 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. * Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.