Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT00995137|
Recruitment Status : Completed
First Posted : October 15, 2009
Last Update Posted : April 26, 2017
|Condition or disease||Intervention/treatment||Phase|
|Lymphoblastic Leukemia, Acute||Biological: NK Cell Infusion||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Genetically Modified Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia|
|Study Start Date :||October 2009|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||May 2014|
Experimental: relapse B-Lineage ALL
All patients meeting the eligibility criteria.
Intervention: NK Cell Infusion
Biological: NK Cell Infusion
Infusing genetically modified NK cells into research participants who have chemotherapy refractory or relapse B-lineage ALL.
- This study will determine the maximum tolerated dose of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL [ Time Frame: 30 days after the enrollment of the last patient ]
- This study will determine the persistence and phenotype of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL. [ Time Frame: 30 days after the enrollment of the last patient ]
- This study will explore the efficacy of genetically modified NK cells in research participants with relapsed or refractory B-lineage ALL. [ Time Frame: 30 days after the enrollment of the last patient ]
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): NCT00995137
|United States, Tennessee|
|St Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105-3678|
|Principal Investigator:||David Shook, MD||St. Jude Children's Research Hospital|