Lenalidomide, Dexamethasone, and Elotuzumab in Treating Patients with Relapsed Primary Amyloidosis

Inclusion Criteria

• Subject must have obtained approval by their insurance to use commercially available lenalidomide and elotuzumab while being treated in the study; if an alternative means of covering the cost of commercial drugs is identified (foundation support, patient drug cost support program, etc.) this is acceptable; please contact the study team at the Karmanos Cancer Institute if any mechanism other than insurance approval is anticipated
• Biopsy-proven histochemical diagnosis of AL amyloidosis based on tissue specimens with Congo red staining or other histologic stain; thioflavin T or S, or crystal violet; tandem mass spec or immunohistochemistry (IHC) confirmation of immunoglobulin-derived amyloidosis is encouraged; cases in which histochemical confirmation is lacking need to be discussed with one of the Multiple Myeloma Research Foundation (MMRF) protocol chair/co-chairs
• At least one prior line of therapy (defined as either one non-transplant regimen such as melphalan [Mel]-dexamethasone [Dex], bortezomib [Vel]-Dex, cyclophosphamide [Cy] bortezomib [Bor] dexamethasone [D], daratumumab, one autologous stem cell transplant, or one regimen of non-transplant induction therapy followed by a single autologous stem cell transplant (without hematologic progression between induction and autologous stem cell transplant [ASCT])
• Measurable hematologic 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) ** Patients without measurable disease according to the dFLC criteria defined above who have a serum M-spike of >= 1.0 g/dL or a urine light chain measurement of >= 200 mg/24 hours (hrs) may be considered eligible; determination of VGPR will be based on International Myeloma Working Group (IMWG) myeloma criteria (Durie DGM, 2006)
• Life expectancy of >= 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Female of child bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL or equivalent units of human chorionic gonadotropin (HCG) within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and study drug and must either commit to continue abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide through 4 weeks after the last dose of lenalidomide and 5 half-lives after elotuzumab plus 30 days (duration of ovulatory cycle) for a total of 180 days post-last dose of elotuzumab; FCBP must also agree to ongoing pregnancy testing during the entire duration of treatment; males must agree to use a latex or synthetic condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 28 days after the last dose of lenalidomide and 5 half-lives of elotuzumab plus 90 days (duration of sperm turnover) for a total of 180 days post-last dose of elotuzumab; these same patients must not donate sperm; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; all patients prior to taking lenalidomide, must be registered in and must comply with all requirements of the lenalidomide Risk Evaluation and Mitigation Strategies (REMS) program * FCBP is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
• Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (1.0 x 10^9/L) (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)
• Platelet count >= 75,000 cells/mm^3 (75 x 10^9/L) (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)
• Hemoglobin >= 8.0 g/dl (red blood cell [RBC] transfusions are permitted) (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)
• Total bilirubin =< 1.5 x ULN (except if the patient has Gilbert’s syndrome who can have total bilirubin =< 2 x ULN) (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)
• Alkaline phosphatase =< 5 x ULN (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x ULN (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)
• Renal function: creatinine clearance by Cockcroft-Gault formula >= 30 mL/min (must be met during screening [within 21 days] and also prior to study drug administration on cycle 1 day 1)

Exclusion Criteria

• Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis; exception: patients with amyloid heavy (AH) or mixed AL/AH type amyloidosis are potentially eligible
• Peripheral neuropathy >= grade 3 sensory neuropathy or >= grade 2 sensory neuropathy with pain within 14 days of registration; prior neuropathy of this severity improved due to medical management such as gabapentin are potentially eligible
• N-terminal fragment brain natriuretic protein (NT-pro)-B-type natriuretic peptide (BNP) > 8500 ng/L
• Medically documented cardiac syncope, uncompensated New York Heart Association (NYHA) class 3 or 4 congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, uncontrolled hypertension (defined as an average systolic blood pressure [SBP] over 140 or a diastolic blood pressure [DBP] over 90 despite antihypertensive agents), clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant; NOTE: there is no lower limit of left ventricular ejection fraction below which patients are excluded from participation
• Any medical conditions that, in the investigator’s opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study, including:
• Known active infection requiring parenteral anti-infective treatment at the time of initiation of treatment
• Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast, or low-risk Gleason grade =< 6 localized prostate cancer not requiring therapy
• Pregnant or breast-feeding females
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
• Known or active human immunodeficiency virus (HIV) infection or active hepatitis B or C viral infection
• Cerebrovascular accident (CVA) with persistent neurologic deficits occurring within 6 months prior to enrollment; persisting neurologic deficits from a CVA occurring over 6 months prior to enrollment are not necessarily grounds for exclusion
• Patients with active symptomatic multiple myeloma as defined by 2015 IMWG criteria (hypercalcemia, renal failure, anemia, bone lesions [CRAB] criteria; bone marrow plasmacytosis > 60%); NOTE: kappa lambda ratio > 100 is acceptable only if the clinical symptoms and signs are attributable only to amyloidosis and not multiple myeloma (i.e., there are no other myeloma-defining CRAB criteria present)
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes)
• Previous cytotoxic therapies, including cytotoxic investigational agents, within 3 weeks (6 weeks nitrosoureas) prior to start of study treatment; previous corticosteroids used with intent to treat amyloidosis within three weeks; (prednisone up to but no more than 10 mg orally once a day [q.d.] or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to study treatment)
• Residual side effects to previous therapy > grade 1 prior to initiation of therapy (alopecia any grade and/or neuropathy grade 2 without pain are permitted)
• Prior autologous stem cell transplant within 12 weeks of initiation of therapy
• Prior major surgical procedure or radiation therapy within 4 weeks of the first dose of study treatment (this does not include limited course of radiation used for management of bone pain within 7 days of first dose of study therapy)
• Known intolerance to steroid therapy (defined as being unable to tolerate at least 20 mg dex/week)
• Inability to tolerate prophylactic anti-thrombotic therapy
• >= grade 3 thromboembolic event in the last 6 months