MT2007-12 Allogeneic Natural Killer Cells With Rituximab in Patients With CD20 Positive Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia. Strategies to Increase Sensitivity of CLL Tumor Cells to Natural Killer Cell-Immune-Mediated Cytolysis
- To determine if allogeneic natural killer (NK) cells infused following
chemoimmunotherapy can be safely expanded in vivo with aldesleukin.
- To determine if interleukin-15 production at day 0 correlates with NK cells expansion.
- To determine overall response rate at 3 months.
- To determine time to progression and overall survival.
- To characterize the quantitative and qualitative toxicities of this treatment plan.
- To determine the incidence of donor products that do not meet release criteria and the
NK cell numbers infused.
- To correlate clinical response with donor/recipient KIR ligand matching status, FcG
receptor 3A genotype, and NK cells phenotype and function
- To determine pharmacodynamic and pharmacogenomic markers and correlate them with NK
cell expansion and disease response.
- Conditioning regimen: Patients receive rituximab intravenously (IV) over 6-8 hours on
days -8, -1, 6, and 13; fludarabine IV on days -6 to -2; and cyclophosphamide IV on day
- Allogeneic natural killer (NK) cell administration: Patients receive
aldesleukin-activated haploidentical NK cells IV over less than 1 hour on day 0. Within
4 hours after allogeneic NK cell infusion, patients receive aldesleukin subcutaneously
(SC) 3 times a week for 6 doses. Patients also receive filgrastim (G-CSF) SC beginning
on day 14 and continuing until absolute neutrophil count (ANC) is > 2,500/mm³ for 2
Patients who achieve a complete or partial response at 28 days are eligible for allogeneic
stem cell transplantation. Patients who achieve initial response at 3 months, clinically
benefit from treatment, but subsequently relapse are eligible for retreatment provided all
eligibility criteria are met.
Blood samples are collected periodically for correlative laboratory studies. Patients with
chronic lymphocytic leukemia (CLL) also undergo bone marrow aspiration periodically for
correlative laboratory studies.
After completion of study treatment, patients are followed periodically for up to 1 year.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients Exhibiting Natural Killer Cell Expansion
Successful natural killer (NK) cell expansion will be defined as an absolute circulating donor-derived NK cell count of >100 cells/μl 14 days after infusion with <5% donor T and B cells in the mononuclear population.
Veronika Bachanova, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center, University of Minnesota||Minneapolis, Minnesota 55455|