Ixazomib Citrate, Cyclophosphamide and Dexamethasone in Treating Newly Diagnosed Participants with Primary Amyloidosis

Inclusion Criteria

• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care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 * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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)
• 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 * Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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) * Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
• Patients must have a diagnosis of biopsy-proven diagnosis of AL amyloidosis according to the following standard criteria: * Histochemical diagnosis of AL amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence and immunohistochemistry * If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary * Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non amyloid forming [uninvolved] free light chain [FLC]) ≥ 50 mg/L) * Systemic amyloid organ involvement including renal, cardiac, gastrointestinal (GI) and/or nervous system involvement as well as soft tissue disease
• Untreated biopsy proven AL amyloidosis
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3
• Hemoglobin ≥ 8.0 g/dL
• Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
• Total bilirubin ≤ 2 × the upper limit of the normal range (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)

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
• 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; recent history of myocardial infarction in the six months prior to registration
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of 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, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
• 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 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 early stage prostate cancer, non melanoma skin cancer or carcinoma in situ of any type are not excluded; patients with malignancies that have undergone complete resection are not excluded
• Patient has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial
• New York Heart Association class III or IV heart failure
• N-terminal pro b-type natriuretic peptide (NT Pro-BNP) > 8500 pcg/mL
• Dialysis dependent renal failure