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

Status: Active

Description

This phase I trial studies the best dose of donor nicotinamide expanded-natural killer cells followed by IL-2 in treating patients with multiple myeloma or CD20 positive non-Hodgkin lymphoma that has come back or does not respond to treatment. Nicotinamide expanded-natural killer cells may improve the natural killer cell cancer killing ability and improve their ability to home into the tumor cells. Interleukins such as IL-2, are proteins made by white blood cells and other cells in the body and may help regulate immune response. Giving nicotinamide expanded-natural killer cells followed by IL-2 may work better in treating patients with multiple myeloma or non-Hodgkin lymphoma.

Eligibility Criteria

Inclusion Criteria

  • 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 with measurable disease defined as serum IgG, A, M M-protein >= 0.5 g/dL or serum IgD M-protein >= 0.5 g/dL, or urine M-protein >= 200 mg/24 hours AND at least at least 4 weeks since plasmapheresis * 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 ** 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 ** Has measurable disease > 1.5 cm in diameter
  • Available HLA-haploidentical or mismatched related donor (aged 12 to 70 years) with donor/recipient match based on a minimum of intermediate resolution deoxyribonucleic acid (DNA) based class I typing of the A and B locus (at least 2/4 class I allele)
  • 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)
  • Absolute neutrophil count (ANC) >= 1000/uL, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
  • Platelet count >= 75,000/uL, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
  • Hemoglobin >= 8.0 g/dL – may be waived if abnormalities are due to disease related bone marrow involvement, 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)
  • Calcium (MM only): corrected calcium < 11.5 mg/dL within 2 weeks prior to study registration
  • 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
  • Voluntary written consent
  • DONOR: 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)
  • 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 a donor infectious disease screen panel including cytomegalovirus (CMV) antibody, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus (HIV) polymerase chain reaction (PCR), HIV ½ antibody, human T-lymphotropic virus antibody (HTLVA) ½ antibody, rapid plasma reagin (RPR), treponema and trypanosoma Cruzi (T. Cruzi), plus nucleic acid testing (NAT) testing (hepatitis B virus [HBV], hepatitis C virus [HCV], West Nile virus [WNV], HIV by nucleic acid method); or per current panel – must be negative for 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: Voluntary written consent (using assent form if donor < 18 years of age)

Exclusion Criteria

  • Active, untreated central nervous system (CNS) involvement
  • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), or high-grade lymphomas (Burkitt’s lymphoma/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
  • 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 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 (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 * Chemotherapy (Chemo) within 3 weeks (6 weeks for melphalan, or monoclonal antibodies)
  • Received investigational drugs within the 14 days before 1st dose of study drug

Locations & Contacts

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Veronika Bachanova
Phone: 612-625-5469
Email: bach0173@umn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the dose of human leukocyte antigen (HLA)-haploidentical or HLA-mismatched related donor, nicotinamide expanded-natural killer (NAM-NK) cells that is most closely associated with a low rate of any grade 4 or greater suspected adverse reaction within 24 hours after the NAM-NK cell infusion or grade III or IV acute graft-versus-host disease (aGVHD) within 28 days after the 1st NAM-NK cell infusion when given after lymphodepleting chemotherapy and followed by a short course of interleukin-2 (IL-2) in adults with relapsed/refractory multiple myeloma (MM) or relapsed/refractory CD20-positive non-Hodgkin lymphoma (NHL).

SECONDARY OBJECTIVES:

I. To evaluate the safety of the therapy as measured by rate of treatment related mortality (TRM) at 2 months.

II. To obtain a preliminary estimate of efficacy as measured by monitoring the rates of disease response at day 28.

III. To evaluate duration of response for up to 1 year from NAM-NK cell infusion.

TERTIARY OBJECTIVES:

I. To describe the incidence of successful in vivo expansion of adoptively transferred NAM-expanded related donor NK cells at day 7 and 14.

II. To examine function of NK cells in peripheral blood at day 7 and 14.

III. To evaluate the presence of donor NK cells in lymph nodes or tumors (marrow) of patients with NHL or MM within 10 days of infusion.

IV. To compare the Panel Reactive Antibody (PRA) score with disease response and NK cell expansion.

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

Patients with MM receive elotuzumab intravenously (IV) on days -10, -3, and 11 and patients with NHL receive rituximab IV on days -10, -3, and 11. Patients also receive fludarabine phosphate IV over 1 hour on days -5, -4, and -3 and cyclophosphamide IV over 2 hours on day -5. Patients then receive NAM-NK cells IV over 15 minutes-1 hour on days 0 and 2 and IL-2 subcutaneously (SC) on days 0, 2, and 4.

After completion of study treatment, patients are followed up for 12 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Veronika Bachanova

Trial IDs

Primary ID MT2015-46
Secondary IDs NCI-2017-02034, 2015LS057
Clinicaltrials.gov ID NCT03019666