Ph I Trial of NAM NK Cells and IL-2 for Adult Pts With MM and NHL

Patient Inclusion Criteria:

- ≥18 to ≤70 years of age

- Meets one of the following disease criteria:

- Multiple Myeloma (MM) meeting one of the following:

- relapsed/refractory disease after two lines of therapies, including a
proteasome inhibitor (bortezomib, carfilzomib or ixazomib) and an
immunomodulatory drug (thalidomide, lenalidomide or pomalidomide)

- relapsed disease between 2-18 months of 1st autologous stem cell
transplantation,

- relapsed disease at least 4 months after allogeneic stem cell
transplantation with no evidence of active graft versus host disease and no
availability of donor lymphocyte infusion

- measurable disease defined as serum IgG, A, M M-protein ≥ 0.5g/dL or serum
IgD M-protein ≥ 0.5 g/dL, or urine M-protein ≥ 200 mg/24 hours

- at least 4 weeks since plasmapheresis

- at least 3 days between last corticosteroids and study treatment start

- CD20-positive B-cell Non-Hodgkin Lymphoma (NHL)

- CD20 expression confirmed by flow cytometry or immunohistochemistry and
meeting one or more of the following:

- evidence of relapsed/refractory disease that has failed conventional
therapy and failed/not eligible/refused studies of a higher priority,

- relapsed disease at least 60 days after autologous stem cell
transplantation

- relapsed disease at least 4 months after allogeneic stem cell
transplantation with no evidence of active graft versus host disease
and no availability of donor lymphocyte infusion

- has measurable disease >1.5 cm in diameter

- HLA-haploidentical or mismatched related donor (aged 12 to 70 years) with
donor/recipient match based on a minimum of intermediate resolution DNA based Class I
typing of the A and B locus (at least 2/4 class I allele) and absence of recipient
anti HLA antibodies against selected donor

- Karnofsky Performance Status ≥ 60% - appendix III

- Adequate organ function within 14 days of study registration (30 days for pulmonary
and cardiac assessments) defined as:

- Bone Marrow: Total white blood cell (WBC) count ≥ 3000/μL, absolute neutrophil
count (ANC) ≥ 1000/μL, platelet count ≥ 75,000/μL and hemoglobin ≥ 8.0 g/dL - may
be waived if abnormalities are due to disease related bone marrow involvement

- Renal: creatinine ≤ 1.5 mg/dL or creatinine clearance ≥40mL/min using
Cockcroft-Gault formula

- Hepatic: ALT or AST ≤ 3 x upper limit of institutional normal (ULN), total
bilirubin ≤ 1.5 x ULN

- Pulmonary Function: oxygen saturation ≥ 90% on room air. If symptomatic or prior
known impairment, pulmonary function ≥ 50% corrected DLCO and FEV1 is required

- Cardiac Function: LVEF ≥ 40%, no uncontrolled angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or
active conduction system abnormalities

- Calcium (MM only): Corrected calcium < 11.5 mg/dL within 2 weeks prior to
enrollment

- Able to be off prednisone or other immunosuppressive medications for at least 3 days
prior to NAM-NK cell infusion (excluding preparative regimen pre-medications)

- Sexually active females of child bearing potential and males with partners of child
bearing potential must agree to use effective contraception during therapy and for 4
months after completion of therapy

- Must have recovered from acute effects of prior therapy - at least 2 weeks should have
elapsed since the last dose of chemotherapy

- Voluntary written consent

Patient Exclusion Criteria:

- Active, untreated CNS involvement

- Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), or high-grade
lymphomas (Burkittt's lymphoma/Lymphoblastic lymphoma)

- Pregnant or breastfeeding - The agents used in this study include those that fall
under Pregnancy Category D - have known teratogenic potential. For elotuzumab arm:
Women of child bearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days of study
treatment start (24 hours prior to the start of elotuzumab)

- Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval
greater than 500 milliseconds)

- Class II or greater New York Heart Association Functional Classification criteria
(appendix III) or serious cardiac arrhythmias likely to increase the risk of cardiac
complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular
ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)

- Active autoimmune disease requiring immunosuppressive therapy

- History of severe asthma, presently on chronic medications (a history of mild asthma
requiring inhaled steroids only is eligible)

- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
unless cleared for study by Pulmonary. Infiltrates attributed to infection must be
stable/improving (with associated clinical improvement) after 1 week of appropriate
therapy (4 weeks for presumed or documented fungal infections).

- Active uncontrolled bacterial, fungal, or viral infections - all prior infections must
have resolved following optimal therapy

- Known hypersensitivity to any of the study agents used

- For MM patients only:

- Prior radiotherapy within 2 weeks prior to the administration of study drug"

- Surgery within 4 weeks

- Chemo within 3 weeks (6 weeks for melphalan, or monoclonal antibodies)

- Received investigational drugs within the 14 days before 1st dose of study drug

- High titer of donor specific anti-HLA antibodies (MFI >1000)

DONOR INCLUSION CRITERIA:

- HLA-haploidentical or mismatched related donor/recipient match based on a minimum of
intermediate resolution DNA based Class I typing of the A and B locus (at least 2/4
class I allele) and absence of recipient anti HLA antibodies

- 12 to 70 years of age - Priority should be given to age (<35 years), followed by HLA
matching (haploidentical and if not available then fully mismatched donor).

- At least 40 kilogram body weight

- In general good health as determined by the evaluating medical provider

- Adequate organ function defined as:

- Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of
normal range of test (gender based for hemoglobin),

- Hepatic: ALT < 2 x upper limit of normal,

- Renal: serum creatinine < 1.8 mg/dl

- Performance of a donor infectious disease screen panel including CMV Antibody,
Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV PCR,
HIV ½ Antibody, HTLVA ½ Antibody, Rapid Plasma (RPR) Treponema , Trypanosoma Cruzi (T.
Cruzi), HCV by NAT, HIV by NAT and WNV (West Nile Virus) by NAT or per current panel -
must be negative for HIV and active hepatitis B

- Not pregnant - females of childbearing potential must have a negative pregnancy test
within 7 days of apheresis

- Able and willing to undergo apheresis

- Voluntary written consent (using assent form if donor < 18 years of age)