Title
Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM)

Description
Phase III study Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma(DETER-SMM)

Objective
The purpose of this study is to determine whether patients with high-risk smoldering multiple myeloma when treated with daratumumab in addition to lenalidomide and dexamethasone live longer when compared to patients with high-risk smoldering multiple myeloma patients treated with lenalidomide and dexamethasone. We would also like to know whether the period of time in which patients are free of multiple myeloma symptoms differs between the two treatment groups

Treatment
Group 1: Daratumumab IV days 1,8,15,and 22 of cycles 1-2, then days 1 and 15 cycles 3-6, then day 1 cycles 7-24, Lenalidomide orally days 1-21, and Dexamethasone days 1,8,15 and 22 for 12 cycles. After the 6th cycles, the dose of dexamethasone will be reduced by 50%. Each cycles lasts 28

Group 2: lenalidomide orally on Days 1-21 for 24 cycles, Dexamethasone orally on Days 1, 8, 15, and 22 for 12 cycles. After the 6th cycle, the dose of dexamethasone will be reduced by 50%. Each cycles lasts 28 days.

Key Eligibility
18 years of age or older

Diagnosed with asymptomatic high-risk(as defined by the protocol) smoldering multiple myeloma (SMM) within the past 12 months

Bone marrow aspirate and/or biopsy is required to be performed within 28 days prior to randomization and must demonstrate 10-59% clonal plasma cells

Measurable disease as defined by the protocol

SPEP, UPEP, and serum FLC are required to be performed within 28 days prior to randomization

Must have no lytic lesions, no known plasmacytoma, and no unexplained hypercalcemia

Adequate hematology, liver and renal function as defined by the protocol

Must not have any prior or concurrent systemic or radiation therapy for the treatment of myeloma. Must also not have contraindication to DVT prophylaxis/aspirin

Must not have more than one focal marrow lesion on MRI of either pelvis or spine

Concurrent use of erythropoietin is not allowed while on study therapy

Prior or glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted

Must not have active, uncontrolled seizure disorder. Must not have had a seizure in the last 6 months

ECOG performance status 0, 1, or 2

Patients with monoclonal gammopathy of undetermined significance are not eligible

No active uncontrolled infection

Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on fulldose
anticoagulation

Should not have New York Heart Association classification III or IV heart failure at baseline

Can not be pregnant or breast feeding

Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled
psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson Syndrome

Male and female of childbearing potential must agree to adequate birth control as defined by the protocol

HIV positive patients with undetectable HIV viral loads tested within 6 months are eligible

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
Mercy Health Systems, Janesville ; UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital