Penostatin, Rituximab and Ontak and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies
Chronic Lymphocytic Leukemia
Biological: Natural killer cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Lymphodepleting Chemotherapy With Rituximab and Allogeneic Natural Killer Cells for Patients With Refractory Lymphoid Malignancies (MT2009-15)|
- Objective Response Rate [ Time Frame: Month 2 Post Infusion ] [ Designated as safety issue: No ]The proportion of patients with an objective response rate (Partial Response +Complete Response) at 2 months post haploidentical NK cell infusion in patient with refractory/relapsed NHL or chronic lymphocytic leukemia (CLL).
- Serious Adverse Events [ Time Frame: Day 1 through Month 12 ] [ Designated as safety issue: Yes ]Number of 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 ] [ Designated as safety issue: No ]Cumulative incidence will be used to determine time to disease progression.
- Patients with Expansion of NK Cells [ Time Frame: Day 14 ] [ Designated as safety issue: No ]Number of patients who experience in vivo expansion of allogeneic donor natural killer (NK) cells.
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
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
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01181258
|Contact: Judith Witte, RNfirstname.lastname@example.org|
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Veronika Bachanova, MD 612-625-5469 email@example.com|
|Contact: Judith Witte, RN 612-626-0169 firstname.lastname@example.org|
|Principal Investigator: Veronika Bachanova, MD|
|Principal Investigator:||Veronika Bachanova, MD||Masonic Cancer Center, University of Minnesota|