Clinical trial NCT01181258
Conditions: Non-Hodgkin Lymphoma Chronic Lymphocytic Leukemia
Keywords: related HLA-haploidentical donor
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2010-08-01; Completion date: 2016-07-01
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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

Arms: arm 1: Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL
Interventions: intervention 1: Rituximab intervention 2: Interleukin-2 intervention 3: Natural killer cells intervention 4: Cyclophosphamide intervention 5: Methylprednisolone intervention 6: Fludarabine
Intervention descriptions: intervention 1: 375 mg/m\^2 administered intravenously (IV) weekly \* 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK) intervention 2: 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. intervention 3: administered intravenously 1.5 to 8 \* 10\^7 cells/kg on Day 0 (day of NK cell infusion) intervention 4: 60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine. intervention 5: 1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion. intervention 6: 25 mg/m\^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through day -2).

Protocol documents: