This is a phase I trial with pilot expansion of HLA-haploidentical or HLA-mismatched related donor nicotinamide expanded-natural killer (NAM-NK) cell based therapy for patients with relapsed or refractory multiple myeloma (MM) or relapsed/refractory CD20-positive non-Hodgkin lymphoma (NHL). The primary endpoint of the study is to determine the maximum tolerated dose (MTD) of NAM-NK cells while maintaining safety.

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)