Study of SubQ Dara With Dose-Attenuated Bortezomib, Lenalidomide, Dexamethasone in Elderly NDMM

Exclusion Criteria

• •Peripheral neuropathy \> Grade 2 or \>Grade 1 with pain on clinical examination during the Screening period.
• •Kidney failure with CrCl ≤ 15 mL/min by Cockfraft Gault
• •Significant cardiac disease as determined by the investigator including:
• •1. Known or suspected cardiac amyloidosis
• •2. Congestive heart failure of Class III or IV of the NYHA classification
• •3. Uncontrolled angina, hypertension or arrhythmia
• •4. Myocardial infarction in the past 6 months
• •5. Any uncontrolled or severe cardiovascular disease
• •6. QTc \> 470 milliseconds (msec) on a 12-lead ECG obtained during the Screening period. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG or by manual calculation.
• •Prior cerebrovascular event with persistent neurologic deficit.
• •Subject is:
• •1. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using realtime polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• •2. Seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• •Human immunodeficiency virus infection
• •Any medical conditions that, in the investigator's opinion, would impose excessive risk to the subject.
• •Prior or concurrent malignancy, except for the following:
• •1. Adequately treated basal cell or squamous cell skin cancer
• •2. Cervical carcinoma in situ
• •3. Adequately treated Stage I or II cancer from which the subject is currently in complete remission.
• •4. Or any other cancer from which the subject has been disease-free for ≥ 3 years
• •Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
• •Males sexually active with females of childbearing potential who do not agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 90 days after the last dose of study drug, or do not agree to practice true abstinence.
• •Central nervous system involvement.
• •Diagnosis of primary amyloidosis (with the exception of patients whose amyloidosis has been documented as a complication of MM, who will be evaluated on a case-by-case basis for trial participation).
• •Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study drug administration.
• •Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal (for subjects \> 65 years old FEV1 \<50% or DLCO \<50%). Note: FEV1 testing is required for subjects suspected of having chronic obstructive pulmonary disease and subjects must be excluded if FEV1 \<50% of predicted normal.
• •Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification. Note: Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study.
• •Persistent corrected serum calcium ≥ 14 mg/dL within 2 weeks of enrollment (despite appropriate measure such a short course of steroids, bisphosphonates, hydration, calcitonin).
• •Absolute neutrophil count \< 1000 cells/mm3. No growth factors allowed within 1 week of enrollment.
• •Platelets \< 75,000 cell/mm3 (75 x 109/L). Qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than 14 days before enrollment. No transfusions are allowed within 72 hours prior to study drug administration.
• •Hemoglobin \< 8 g/dL. Qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than 14 days before enrollment. No transfusions are allowed within 72 hours before qualifying laboratory value.
• •Total bilirubin \> 1.5 x ULN, unless known have Gilbert's syndrome in which case 3 x ULN).
• •AST or ALT ≥ 3 x ULN.
• •Major surgery or radiation therapy within 14 days before study drug administration.
• •Kyphoplasty or vertebroplasty within 1 week of enrollment.
• •Administration of Anti-myeloma chemotherapy, biological, immunotherapy, or investigational agent (therapeutic or diagnostic) within 3 weeks before enrollment; however, a cumulative dose of ≤ 160 mg dexamethasone or equivalent during screening is permitted.
• •NSAIDs, IV contrast, aminoglycosides, or other potentially nephrotoxic drugs within 2 weeks of enrollment, except aspirin.
• •Known hypersensitivity to bortezomib, lenalidomide, dexamethasone, or daratumumab