Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma

PRIMARY OBJECTIVES:

I. To find the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived natural
killer (NK) cells.

II. To determine efficacy by the percent of patients achieving very good partial remission
(VGPR) + complete remission (CR) at 3 months post-transplant.

III. To assess the minimal residual disease rate 100 days post-transplant in high-risk
patients.

SECONDARY OBJECTIVES:

I. To quantify duration of infused allogeneic donor UCB-derived NK cells in the recipient.

OUTLINE: This is a dose-escalation study of UCB-derived NK cells.

Patients receive elotuzumab intravenously (IV) over 2-5 hours on day -15 and -8, lenalidomide
orally (PO) once daily (QD) on days -8 to -2, high-dose melphalan IV over 30 minutes on day
-7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell
transplant on day 0.

After completion of study treatment, patients are followed up on days 30 and 100.

Inclusion Criteria:

- Patients with high risk multiple myeloma who are transplant candidates, in partial
response (PR) or better; high risk will be defined as patients with any of the
following:

- Fluorescence in situ hybridization showing t(4:14), t(14:16)t (14:20) deletion
(Del) 17/17p or gain (amp) 1q;

- Deletion 13 by conventional cytogenetic analysis;

- High risk signatures as determined by the GEP-70 or EMC-92 gene expression
profiles;

- Relapsed disease within 18 months of prior autologous stem cell transplant (ASCT)

- Patients with plasma cell leukemia who are transplant candidates

- Performance score of at least 70% by Karnofsky or 0 to 2 Eastern Cooperative Oncology
Group (ECOG)

- Left ventricular ejection fraction greater than 40%

- Pulmonary function test (PFT) demonstrating a diffusion capacity of least 40%
predicted

- Estimated serum creatinine clearance >= 60 ml/min (using the Cockroft-Gault formula
and/or serum creatinine =< 1.6 mg/dL

- Serum glutamate pyruvate transaminase (SGPT) less than 3 x upper limit of normal

- Total bilirubin less than 2 x upper limit of normal

- All study participants must be registered into the mandatory Revlimid Risk Evaluation
and Mitigation Strategy (REMS) program, and be willing and able to comply with the
requirements of the Revlimid REMS program

- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS program

- Men must agree to use a latex condom during sexual contact with females of child
bearing potential even if they have had a successful vasectomy

- Patients must have a cord blood (CB) unit available which is matched with the patient
at 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular)
antigens

- Availability of autologous peripheral blood stem cell graft, containing at least 6.0 x
10^6 cluster of differentiation 34 positive (CD34+) cells/kg except those with
relapsed disease within 18 months of prior ASCT, who should have at least 2.5 x 10^6
CD34+ cells/kg available

- Patient or legally authorized representative able to sign informed consent

Exclusion Criteria:

- Patients receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to melphalan

- Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, uncontrolled hypertension (systolic > 160, diastolic > 100 despite
antihypertensive therapy, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements

- Human immunodeficiency virus (HIV)-positive patients are excluded