NCT00995137

Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia

Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will determine the maximum tolerated dose of genetically modified natural killer (NK) cells in research participants with relapsed or refractory B-lineage acute lymphoblastic leukemia (ALL).

Detailed description

NK cell cytotoxicity is most powerful against acute myeloid leukemia (AML) cells, whereas their capacity to lyse ALL cells is generally low and difficult to predict. A novel method has been developed to redirect NK cells towards CD19, a molecule highly expressed on the surface of B-lineage ALL cells, but not expressed on normal cells other than B-lymphocytes. In this method, donor NK cells are first expanded by co-culture with irradiated K562 cell line modified to express membrane bound IL-15 and 41BB ligand (K562-mb15-41BBL). Overexpansion of these proteins promotes selective growth of NK cells. Then, the expanded NK cells are transduced with a signaling receptor that binds to CD19 (anti-CD19-BB-zeta). NK cells expressing these receptors showed powerful anti-leukemic activity against CD19+ ALL cells in vitro and in an animal model of leukemia. This study represents the translation of laboratory findings into clinical application. It will allow us to assess the safety of infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL. In this same cohort, we also intend to study the in vivo lifespan and phenotype of genetically modified NK cells and explore the efficacy of NK cells in patients with B-lineage ALL.

Conditions

• Lymphoblastic Leukemia, Acute

Interventions

Type	Name	Description
BIOLOGICAL	NK Cell Infusion	Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.

Timeline

• Start date: 2009-10-01
• Primary completion: 2013-05-01
• Completion: 2014-05-01
• First posted: 2009-10-15
• Last updated: 2017-04-26

Locations

1 site across 1 country: United States