Penostatin, Rituximab and Ontak and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies
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|ClinicalTrials.gov Identifier: NCT01181258|
Recruitment Status : Completed
First Posted : August 13, 2010
Results First Posted : May 18, 2017
Last Update Posted : February 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma Chronic Lymphocytic Leukemia||Drug: Rituximab Biological: Interleukin-2 Biological: Natural killer cells Drug: Cyclophosphamide Drug: Methylprednisolone Drug: Fludarabine||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Lymphodepleting Chemotherapy With Rituximab and Allogeneic Natural Killer Cells for Patients With Refractory Lymphoid Malignancies (MT2009-15)|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||July 2016|
Experimental: Patients Receiving NK Cell Infusion
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
375 mg/m^2 administered intravenously (IV) weekly * 4, (day -7, -1, +6, +13) pre-infusion with natural killer cells (NK)
Other Names: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.
Other Name: IL-2Biological: Natural killer cells
administered intravenously 1.5 to 8 * 10^7 cells/kg on Day 0 (day of NK cell infusion)
Other Name: NK cellsDrug: Cyclophosphamide
60 mg/kg administered intravenously (IV) for 2 hours on day -5 after Fludarabine.
Other Name: CytoxanDrug: Methylprednisolone
1 mg/kg on Days -2 through +9 as an intravenous (IV) infusion.
Other Name: MedrolDrug: Fludarabine
25 mg/m^2/day administered as a 1 hour IV infusion once a day for 5 doses (day -6 through day -2).
Other Name: Fludara
- Number of Patients With an Objective Response [ Time Frame: Month 2 Post Infusion ]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.
- Serious Adverse Events [ Time Frame: Day 1 through Month 12 ]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 to Disease Progression [ Time Frame: Day 1 through Month 12 ]Cumulative incidence will be used to determine time to disease progression.
- Patients With Expansion of NK Cells [ Time Frame: Day 14 ]Number of patients who experience in vivo expansion of allogeneic donor natural killer (NK) cells.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01181258
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Veronika Bachanova, MD||Masonic Cancer Center, University of Minnesota|