S1211, Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma

RATIONALE: Lenalidomide and bortezomib may stop the growth of multiple myeloma by blocking
blood flow to the tumor. Also, bortezomib may stop the growth of tumor cells by blocking
some of the enzymes needed for cell growth. Monoclonal antibodies, such as elotuzumab, can
block cancer growth in different ways. Some block the ability of cancer cells to grow and
spread. Others find cancer cells and help kill them or carry cancer-killing substances to
them. Drugs used in chemotherapy, such as lenalidomide and dexamethasone also work in
different ways to kill tumor cells or stop them from growing. Giving elotuzumab together
with chemotherapy may be a better way to block cancer growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of elotuzumab and
to see how well it works when given with lenalidomide, bortezomib, and dexamethasone in
treating patients with multiple myeloma.

Eligibility Criteria


- Patients must have newly diagnosed active multiple myeloma (MM)

- Patients with non-secretory MM or known amyloidosis are not eligible

- For the Phase II portion only, patients must have high-risk MM based on one or more
of the following criteria at the time of initial diagnosis (prior to any

- Poor-risk genomic signature according to the University of Arkansas 70-gene
model (available clinically as MyPRS score, Signal Genetics, Inc.)

- Translocation (14;16), and/or translocation (14;20), and/or deletion (17p) by
florescence in-situ hybridization (FISH) or cytogenetics

- Primary plasma cell leukemia (defined by either ≥ 2,000 plasma cells/mL of
peripheral blood, or 20% on a manual differential count

- Serum lactate dehydrogenase (LDH) ≥ 2 times institutional upper limit of normal

- Patients must have measurable disease within 28 days prior to registration (or prior
to initiation of first induction course for patients with prior therapy)

- Patients on the Phase I portion may not have received ANY prior chemotherapy

- Patients on the Phase II portion may have received one prior cycle of any
noninvestigational chemotherapy

- Patients must not have active involvement of the central nervous system (CNS) with MM
(by clinical evaluation)

- Patients with documentation of or clinical signs or symptoms consistent with CNS
involvement by MM must have a lumbar puncture that is negative for CNS

- Patients with no previous history of documented CNS involvement and with no
clinical signs or symptoms consistent with CNS involvement are not required to
have completed a lumbar puncture prior to registration


- Zubrod performance status ≤ 2

- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm³ without growth factor support

- Platelet count ≥ 70,000 cells/mm³ for patients who have bone marrow plasmacytosis <
50% OR ≥ 50,000 cells/mm³ for patients who have bone marrow plasmacytosis of ≥ 50%

- Total bilirubin ≤ 1.5 times institutional upper limit of normal (IULN)

- Serum glutamic oxalo-acetic transaminase (SGOT)/aspartate aminotransferase (AST) and
serum glutamic pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) ≤ 2.5
times IULN

- Creatinine clearance (CrCL) ≥ 30 mL/min

- Patients who are known to be human immunodeficiency virus (HIV)-positive are eligible
providing they meet all of the following additional criteria within 28 days prior to

- CD4 cells ≥ 500/mm³

- Viral load of < 50 copies HIV mRNA/mm³ if on antiretroviral therapy (ART) or <
25,000 copies HIV mRNA if not on ART

- No zidovudine or stavudine as part of ART

- Patients must have baseline skeletal survey to document lytic lesions, osteopenia, or
compression fracture

- Patients with known hepatitis B or hepatitis C infection may be eligible providing
they have viral load < 800,000 IU/L within 28 days prior to registration

- Patients must not have POEMS syndrome (plasma cell dyscrasia with polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes)

- Patients must not have clinically significant illness including any of the following:

- Uncontrolled, active infection requiring intravenous antibiotics

- New York Heart Association (NYHA) Class III or Class IV heart failure

- Unstable angina pectoris

- Myocardial infarction within the past 6 months

- ≥ Grade 3 cardiac arrhythmias per Common Terminology Criteria for Adverse Events
(CTCAE) Version 4.0

- Patients must have undergone an electrocardiogram (EKG) within 28 days
prior to registration

- Uncontrolled blood pressure (BP) or hypertension

- Defined as systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg within 14
days prior to registration

- An exception can be made by a healthcare provider for a patient with a
single BP elevation who, upon rechecking, has a normal BP

- Patients are permitted to be receiving multiple antihypertensive
medications (unless otherwise indicated in the study)

- Uncontrolled diabetes mellitus (defined as a glycosylated hemoglobin A1C (Hg
A1C) > 7% within 14 days prior to registration)

- The same criterion will be used in patients with confirmed diagnosis of
diabetes mellitus who have been on a stable dietary or therapeutic regimen
for this condition in the last three months

- Patients must not have any psychiatric illness that could potentially interfere with
the completion of treatment according to this protocol

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to

- FCBP must either commit to continued 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 28 days before starting
lenalidomide and continuing for at least 4 months after completion of study therapy

- Men must agree to use a latex condom during sexual contact with a FCBP, even if
they have had a successful vasectomy

- Not pregnant or breastfeeding

- 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 five years


- See Disease Characteristics

- Prior chemotherapy must have been completed within 56 days prior to registration and
all toxicities must have resolved to ≤ Grade 1

- Patients may have received prior radiotherapy for symptomatic localized bone lesions
or impending spinal cord compression only

- Radiotherapy must be completed at least 14 days prior to registration and all
toxicities must have resolved to ≤ Grade 1

Principal Investigator

Peter VanVeldhuizen

Study Contact

Kelly Daniels, kdaniels2@kumc.edu

Estimated Completion Date

Thursday, November 1, 2018

ClinicalTrials.gov #