In this study the investigators investigate a cell therapy strategy that could harness allogeneic effectors that can potentially mediate anti-lymphoma effect. The investigators have designed a novel lymphodepleting conditioning regimen followed by infusion of donor-derived natural killer (NK) cells and interleukin-2 (IL-2) for patients with refractory lymphoid malignancies.
This is a single center phase II trial designated to expand donor NK cells and induce remissions in patients with refractory non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) using chemotherapy followed by haploidentical NK cells and IL2. Primary Objective is to evaluate the objective response rate (PR+CR) at 2 months post haploidentical NK cell infusion in patients with refractory Non Hodgkin's Lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Secondary Objective is to 1) evaluate the safety and tolerability of lymphodepleting chemotherapy, rituximab, and methylprednisone as determined by incidence of serious adverse events; 2) evaluate in vivo expansion of allogeneic donor NK cells at day 14; 3) determine time to progression Exploratory Objective is to 1) correlate clinical response with frequencies of peripheral blood T reg cells after chemotherapy; 2) correlate clinical response with donor KIR-B-content score determined by genotype; 3) monitor phenotypic and functional characteristics of natural killer cells and regulatory T cells in vivo; 4) correlate clinical response with donor FcR polymorphism. * Pre-NK cell infusion chemotherapeutic regimen consist of 1) Rituximab 375mg/m2 IV weekly x 4, start day -7; 2) Fludarabine 25 mg/m2 IV day -6 through day -2; 3) Cyclophosphamide 60mg/kg IV day -5; 4) Methylprednisolone 1 mg/kg day -2 through day +9. * NK cell infusion using IL2 activated donor NK cells 1.5 to 8 x 107 cells/kg IV day 0 * IL2 SC 9 million IU every other day x 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight \< 45 kilograms, give IL-2 at 5 million units/m2 on same schedule Accrual Goal: Up to 17 patients will be enrolled
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
375 mg/m\^2 administered intravenously (IV) weekly \* 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK)
subcutaneously administered 9 million international units (IU) every other day \* 6 doses over 2 weeks begin 1 to 24 hours after NK cell infusion. If weight \< 45 kilograms, give IL-2 at 5 million units/m2 on same schedule.
administered intravenously 1.5 to 8 \* 10\^7 cells/kg on Day 0 (day of NK cell infusion)
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Number of Patients With an Objective Response
The number of patients with a partial response (PR) or complete response (CR). For patients with non-hodgkin's lymphoma: CR - complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR - at least a 50% decrease in sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. For patients with chronic lymphocytic leukemia: CR - disappearance of all palpable disease, normalization of the blood counts without transfusions, bone marrow aspirate lymphocyte percentage \< 30%, and no evidence of disease on bone marrow biopsy. PR - 50% or more reduction in palpable disease as well as one or more of the remaining features: neutrophils \>= 1.5 × 109/L or 50% improvement over baseline, platelets more than 100 × 109/L or 50% improvement over baseline, and hemoglobin more than 11.0 g/dL or 50% improvement over baseline without transfusions.
Time frame: Month 2 Post Infusion
Serious Adverse Events
Number of participants experiencing serious adverse events that occur during study. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL2 injections.
Time frame: Day 1 through Month 12
Time to Disease Progression
Cumulative incidence will be used to determine time to disease progression.
Time frame: Day 1 through Month 12
Patients With Expansion of NK Cells
Number of patients who experience in vivo expansion of allogeneic donor natural killer (NK) cells.
Time frame: Day 14
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NONE
Enrollment
16
60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine.
1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion.
25 mg/m\^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through day -2).