Donor Nicotinamide Expanded-Natural Killer Cells Followed by IL-2 in Treating Patients with Relapsed or Refractory Multiple Myeloma or CD20 Positive Non-Hodgkin Lymphoma

Inclusion Criteria

• Meets one of the following disease criteria: * Aggressive CD20-positive B-cell non-Hodgkin lymphoma (NHL) with diagnosis of diffuse large B cell lymphoma, follicular lymphoma grade IIIb, aggressive B-cell lymphoma and its variants ** 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 *** 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 has measurable disease > 1.5 cm in diameter * Indolent CD20-positive B-cell Non-Hodgkin Lymphoma (NHL) with diagnosis of: ** Follicular lymphoma grade I, II, IIIa ** Lymphoplasmacytic lymphoma ** Waldenstrom macroglobulinemia ** Marginal zone lymphoma (nodal, splenic, extranodal) ** Mucosa-associated lymphoid tissue (MALT) lymphoma ** Small lymphocytic lymphoma or chronic lymphocytic leukemia (CLL) ** Other indolent B-cell non-Hodgkin lymphoma ** 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 *** 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 has measurable disease > 1.5 cm in diameter
• Available HLA-haploidentical or mismatched related donor (aged 12 to 70 years). With the January 2021 version the definition of related was expanded to include non-biologic relatives (e.g. spouse/partner, half/adopted siblings, step or adopted offspring)
• Karnofsky performance status >= 60%
• Total white blood cell (WBC) count >= 3000/uL, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
• Creatinine =< 1.5 mg/dL or creatinine clearance >= 40 mL/min using Cockcroft-Gault formula, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3 x upper limit of institutional normal (ULN), within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
• Total bilirubin =< 1.5 x ULN, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
• Oxygen saturation >= 90% on room air; if symptomatic or prior known impairment, pulmonary function >= 50% corrected diffusing capacity of the lungs for carbon monoxide (DLCO) and forced expiratory volume (FEV)1 is required, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
• Left ventricular ejection fraction (LVEF) >= 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
• 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
• Provides voluntary written consent
• COMPASSIONATE RE-TREATMENT: The patient had stable disease (SD), partial response (PR), or a complete response (CR) from the initial study treatment
• COMPASSIONATE RE-TREATMENT: A minimum of 60 days has passed since the 1st NAM-NK cell infusion and the day +60 visit must have occurred
• COMPASSIONATE RE-TREATMENT: The original donor agrees to a 2nd cell collection procedure
• COMPASSIONATE RE-TREATMENT: The patient experienced no dose limiting equivalent toxicities with the 1st treatment course
• COMPASSIONATE RE-TREATMENT: The patient voluntarily signs the re-treatment consent
• DONOR: HLA-haploidentical or mismatched related donor/recipient with the January 2021 version the definition of related was expanded to include non-biologic relatives (e.g. spouse/partner half/adopted siblings, step or adopted offspring)
• DONOR: 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)
• DONOR: At least 40 kilogram body weight
• DONOR: In general good health as determined by the evaluating medical provider
• DONOR: Hemoglobin within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• DONOR: WBC within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• DONOR: Platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• DONOR: ALT < 2 x upper limit of normal
• DONOR: Serum creatinine < 1.8 mg/dl
• DONOR: Performance of the current institutional donor infectious disease screen panel – must be negative for human immunodeficiency virus (HIV) and active hepatitis B
• DONOR: Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of apheresis
• DONOR: Able and willing to undergo apheresis
• DONOR: Provides voluntary written consent (using assent form if donor < 18 years of age)

Exclusion Criteria

• Active, untreated central nervous system (CNS) involvement
• Burkitt lymphoma and lymphoblastic lymphoma
• Pregnant or breastfeeding; 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 human chorionic gonadotropin [HCG]) within 14 days of study treatment start (24 hours prior to the start of elotuzumab)
• Marked baseline prolongation of QT/corrected QT interval (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
• Class II or greater New York Heart Association Functional Classification criteria 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
• New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (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 (2 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
• Time between previous treatment and 1st dose of study drug (disease specific monoclonal antibody): * Surgery within 4 weeks * Chemotherapy within 2 weeks (6 weeks for melphalan) * Monoclonal antibodies within 2 weeks (does not apply to rituximab, elotuzumab) * Immunomodulatory imide drugs (ImiDs), proteasome inhibitors, Bruton's tyrosine kinase (BTK) inhibitors and PI3 kinase inhibitors and other oral disease modifying anti-cancer therapies within 3 days (does not apply to pomalidomide) * There are no timing restrictions for the use of palliative radiation therapy
• Received investigational drugs within the 14 days before 1st dose of study drug
• Current or past diagnosis of plasma cell leukemia