NCT01181258

Penostatin, Rituximab and Ontak and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies

Lymphodepleting Chemotherapy With Rituximab and Allogeneic Natural Killer Cells for Patients With Refractory Lymphoid Malignancies (MT2009-15)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

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

Conditions

• Non-Hodgkin Lymphoma
• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	Rituximab	375 mg/m\^2 administered intravenously (IV) weekly \* 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK)
BIOLOGICAL	Interleukin-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.
BIOLOGICAL	Natural killer cells	administered intravenously 1.5 to 8 \* 10\^7 cells/kg on Day 0 (day of NK cell infusion)
DRUG	Cyclophosphamide	60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine.
DRUG	Methylprednisolone	1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion.
DRUG	Fludarabine	25 mg/m\^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through day -2).

Timeline

• Start date: 2010-08-01
• Primary completion: 2015-09-01
• Completion: 2016-07-01
• First posted: 2010-08-13
• Last updated: 2018-02-06
• Results posted: 2017-05-18

Locations

1 site across 1 country: United States