Testing the Investigational Agent Combination of Daratumumab, Bortezomib, and Dexamethasone Compared to the Usual Treatment of Cyclophosphamide, Bortezomib, and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients With Kidney Failure

3.1.1 Patient must be ≥ 18 years of age. 3.1.2 Patient must have an ECOG Performance Status 0-2. NOTE: ECOG Performance Status 3 patients are eligible if attributable to pathological fractures and/or cancer-related bone pain. 3.1.3 Patient must have multiple myeloma and meet BOTH of the following criteria for the original diagnosis of myeloma following the International Myeloma Working Group (IMWG) myeloma diagnostic criteria within 90 days prior to randomization. 1. Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma. Plasma cell % on Bone Marrow \_\_\_\_\_\_ (%) Date of test:\_\_\_\_\_\_\_ Tissue biopsy of any bone lesion or extramedullary plasmacytoma if applicable (Positive / Negative for Clonal Plasma Cells) Date of test:\_\_\_\_\_\_\_ 2. Any one or more of the following myeloma-defining events: * Anemia (hemoglobin value of \>2 g/dL below the lower limit of normal, or a hemoglobin value \<10 g/dL) * Hypercalcemia (serum calcium \>1 mg/dL higher than the upper limit of normal or \>11 mg/dL) * Bone disease (one or more osteolytic lesions on skeletal radiography, CT, or FDG-PET/CT) * Renal dysfunction (creatinine clearance \< 40 mL/min or serum creatinine \>2 mg/dL). * Clonal BMPCs ≥60% * Involved: uninvolved serum free light chain ratio ≥100 * \> 1 focal lesions on MRI studies ≥5 mm NOTE: Patients with smoldering myeloma (serum m protein ≥ 3 gm/dL or bone marrow plasma cells ≥ 10% plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein \< 3 gm/dL and bone marrow plasma cells \< 10% plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible. 3.1.4 Patient must have newly diagnosed (within the last 90 days) light chain cast nephropathy (LCCN) defined as patients with \>1 g/dl proteinuria with \<10% albuminuria, and/or an involved serum free light chain (FLC) concentration \>150 mg/dL. 3.1.5 Patient must have new onset of renal failure (within the last 90 days). Patient must have met one of the following criteria: * Any serum creatinine who have an eGFR of \<40 ml/min/1.73 m2 calculated with the Modification of Diet in Renal Disease (MDRD) formula * Serum creatinine \>2 mg/dL * On dialysis NOTE: eGFR must be \< 50 ml/min/1.73 m2 if eligible based on serum creatinine level and/or dialysis. NOTE: The MDRD formula38 (mL/min/1.73 m2) = GFR = 175 x SCr-1.154 × age-0.203 × 0.742 (if female) × 1.212 (if black) SCr: \_\_\_\_\_\_\_\_ Date of Test: \_\_\_\_\_\_\_\_\_\_\_\_\_ GFR: \_\_\_\_\_ (mL/min/1.73 m2) Date of calculation: \_\_\_\_\_\_\_\_ 3.1.6 Patient may have received myeloma targeting therapy including any of the following: cyclophosphamide, bortezomib and/or dexamethasone, as long as it was no more than one cycle AND the last dose administered was within 30 days prior to randomization. NOTE: There is no washout period required. 3.1.7 Patient may have received plasma exchange to treat LCCN within 30 days prior to randomization. 3.1.8 Patient must not have been exposed to any prior or currently be on any anti-CD38 monoclonal antibodies. 3.1.9 Patients who have received prior investigational drug (including investigational vaccine) or invasive investigational medical device for any indication must have recovered from clinically significant adverse events prior to randomization. 3.1.10 Patient must not have current or prior exposure to focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. 3.1.11 Patient must have SPEP, UPEP, and serum FLC assays performed within 28 days prior to randomization. In addition, a bone marrow biopsy and/or aspirate and/or tissue biopsy of any bone lesion or extramedullary plasmacytoma is required to be performed within 28 days prior to randomization. Serum M-protein by SPEP: \_\_\_\_\_\_\_ (g/dL) Date of SPEP test:\_\_\_\_\_\_\_ Urine M-protein by 24 hr UPEP: \_\_\_\_\_\_\_ (mg/24 hr) Date of UPEP test:\_\_\_\_\_\_\_ NOTE: UPEP (on a 24 hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is ≥ 200 mg/24 hr. If both serum and urine M-components are measurable, both must be followed in order to confirm response. Serum Free Light Chain Assay Date of Light Chain Assay test:\_\_\_\_\_\_\_ Kappa FLC:\_\_\_\_\_\_\_ (mg/dL) or \_\_\_\_\_\_\_ (mg/L) Lambda FLC:\_\_\_\_\_\_\_ (mg/dL) or \_\_\_\_\_\_\_ (mg/L) Kappa/lambda ratio:\_\_\_\_\_\_\_ NOTE: The serum free light chain test is required to be done monthly if the patient does not have measurable disease in the serum or urine. 3.1.12 Patient must have adequate bone marrow function as defined below (these labs must be obtained \< 28 days prior to randomization): Hemoglobin ≥ 7.5 g/dL (≥ 4.65 mmol/L). Use of prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted. Hgb: \_\_\_\_\_\_\_\_\_\_ Date of Test:\_\_\_\_\_\_\_\_\_\_ Absolute Neutrophil Count (ANC) \> 1000 mcL ANC:\_\_\_\_\_\_\_\_\_\_ Date of Test:\_\_\_\_\_\_\_\_\_\_ Platelets \> 75,000 mcL. Prior platelet transfusion is permitted. Platelets:\_\_\_\_\_\_\_\_\_\_ Date of Test:\_\_\_\_\_\_\_\_\_\_ 3.1.13 Patient must have adequate hepatic function as defined below (these labs must be obtained ≤ 28 days prior to randomization): Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) Total Bilirubin:\_\_\_\_\_\_\_\_\_\_ Institutional ULN:\_\_\_\_\_\_\_\_\_ Date of Test:\_\_\_\_\_\_\_\_\_\_ AST(SGOT) and ALT(SGPT) ≤ 3 × institutional ULN AST:\_\_\_\_\_\_\_ Institutional ULN:\_\_\_\_\_\_\_\_\_ Date of Test:\_\_\_\_\_\_\_ ALT: \_\_\_\_\_\_\_Institutional ULN:\_\_\_\_\_\_\_\_\_ Date of Test:\_\_\_\_\_\_\_ 3.1.14 Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Patient of child bearing potential? \_\_\_\_\_\_ (Yes or No) Date of blood test or urine study: \_\_\_\_\_\_\_\_\_\_\_ 3.1.15 Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the treatment phase of the study. Patients of childbearing potential must agree to continue contraceptive measures for at least 1 year after the last dose of Arm A protocol treatment and for at least 7 months after the last dose of Arm B protocol treatment. Patients who can father children with partners who could become pregnant must agree to continue contraceptive measures for at least 4 months after the last dose of protocol treatment. Patient must not donate eggs (ova, oocytes) or sperm while on protocol treatment and for 4 weeks after the last dose of daratumumab-hyaluronidase. 3.1.16 Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible. 3.1.17 Patients with a history of respiratory disease within the past 2 years (i.e. chronic obstructive pulmonary disease, moderate or severe persistent asthma) must have a forced expiratory volume in 1 second (FEV1) ≥ 50% of predicted normal (obtained within ≤ 28 days prior to randomization) to be eligible. Patients with current uncontrolled asthma of any classification are not eligible. 3.1.18 Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better. 3.1.19 Patients with a history of human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy with an undetectable viral load within 6 months of randomization to be eligible for this trial. 3.1.20 For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. 3.1.21 Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients who completed treatment for hepatitis C at least 6 months prior to randomization and have no detectable circulating HCV are eligible. 3.1.22 Patient must not have grade 3 or 4 peripheral neuropathy at the time of randomization. 3.1.23 Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial 3.1.24 Patient must not have AL amyloidosis (amyloid light chain or primary amyloidosis), plasma cell leukemia, or CNS involvement. 3.1.25 Patient must not have known allergies, hypersensitivity, or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients.