A Phase II Study of Isatuximab (SAR650984) for Patients with Previously Treated AL Amyloidosis

-Pt must have relapsed or refractory primary systemic AL Amyloidosis.

-Pt must have measurable disease within 28 days prior to reg and serum beta2 microglobulin, IgG, IgA, and IgM, serum free kappa and lambda, SPEP with M-protein quant, and urine immunofixation electrophorsis within 14 days prior to reg.

-Pt must demonstrate a difference in the involved serum free light chains (kappa or lambda) versus the uninvolved serum free light chain of >/= 4.5mg/dL within 14 days prior to reg.

-Pt must have objective organ involvement of kidney, heart, liver, GI tract, autonomic or peripheral nervous system and/or soft tissue.

-Pts must not have active symptomatic MM by 2015 IMWG criteria.

-Pt must be relapsed or refractory to at least one prior line of therapy.

-Pts must have completed other systemic therapy >/= 14 days or investigational drug >/= 28 days prior to reg, surgery (other than biopsies) >/= 21 days prior to reg, and ASCT >/= 100 days prior to reg.

-Pts must not have received any supplements with known anti-amyoidogenic effect within 14 days prior to reg.

-Pts must not have any known allergies to isatuximab or other monoclonal antibody therapies.

-Pts must not have received or been refractory to daratumumab within 56 days prior to reg.

-Pts must not be eligible for ASCT.

-Pts must have a complete medical history and physical exam within 14 days prior to reg.

-Patients must be >/= 18 years of age.

-Pts must have adequate hepatic function within 14 days prior to registration (Total bilirubin </= 2.0 x IULN AND AST and ALT </= 4.0 x IULN.

-Pts must have adequate renal function (CrCl) >/= : 25 mL/min by a 24-hour urine or estimated by Cockcroft and Gault (serum creatinine value used in the calculation must have been obtained within 35 days prior to reg).

-Pts must have bone marrow aspirate, including FISH (including: del 17p; t11;14; t4;14, t14;16; and del 13q) and cytogenetics (normal - XY; and all abnormalities) within 35 days prior to registration.

-Pts must have adequate bone marrow function within 14 days prior to (ANC >/= 1,000 cells/mcl without GF, AND platelets >/= 75,000 cells/mcl).

-Pts must have hemoglobin >/= 8 g/dL within 14 days prior to reg (no transfusion within 7 days prior to reg).

-Pts must have adequate cardiac function (NYHA < Class IV heart failure AND LVEF by ECHO >/= 35% within 35 days prior to reg AND NT-proBNP </= 8500 ng/L within 14 days prior to reg).

-Pts must have a Zubrod Performance Status </= 2.

-Pts must not have any clinically significant uncontrolled systemic illness within the past 6 months, uncontrolled cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes mellitus.

-FCBP must have a negative pregnancy test within 14 days prior to reg and must agree: (1) to have a pregnancy test prior to the start of each treatment cycle and (2) to either commit to continued abstinence or to use effective contraception while receiving study drug and for at least 12 weeks after receiving the last dose of study drug.

-Pts with evidence HBV must have minimal hepatic injury and the undetectable HBV on suppressive HBV therapy. Pt must be willing to maintain adherence to HBV therapy. Pts with previously treated and eradicated HCV who have minimal hepatic injury are eligible.

-Pts who are known to be HIV-positive at reg must have undetectable HIV viral load by PCR, be willing to maintain adherence to combination antiretroviral therapy, have no history of AIDS defining condition (other than CD4 cell count <200mm3), and be otherwise likely to have a near normal lifespan if not for the presence of relapsed/refractory amyloid.

-No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least two years.

-Pts must be offered participation in specimen banking.

-Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.