Pilot Study of Redirected Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT01974479|
Recruitment Status : Suspended (Suspended for an interim review of (CAR) CD19 research strategy for the treatment of CD19 positive ALL.)
First Posted : November 1, 2013
Last Update Posted : April 12, 2019
Modern therapy for patients with B-lineage acute lymphoblastic leukemia (ALL) is based on intensive administration of multiple drugs. In patients with relapsed disease, treatment response is generally poor; for most patients, particularly those who relapse while still receiving frontline therapy, the only therapeutic option is hematopoietic stem cell transplantation (HSCT). There is no proven curative therapy for patients who relapse after transplant.
Natural killer (NK) cells have powerful anti-leukemia activity. In patients undergoing allogeneic HSCT, several studies have demonstrated NK-mediated anti-leukemic activity. NK cell infusions in patients with leukemia have been shown to be well tolerated and void of graft-versus-host disease (GVHD) effects.
NK cell cytotoxicity is most powerful against acute myeloid leukemia (AML) cells, whereas their capacity to lyse ALL cells is generally low. We have developed a novel method to expand and 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 the cell line K562-mb15-41BBL and interleukin (IL)-2. 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 will assess the feasibility, safety and efficacy of infusing expanded, activated redirected NK cells into research participants with B-lineage ALL who have persistent disease after intensive chemotherapy . In this same cohort, we will study the in vivo lifespan and phenotype of these redirected NK cells.
|Condition or disease||Intervention/treatment||Phase|
|B-cell Acute Lymphoblastic Leukemia||Biological: anti-CD19 redirected NK cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||To determine the feasibility, safety and efficacy of anti-CD19 redirected NK cells infusion in research participants with B-Lineage Acute Lymphoblastic Leukemia (B-ALL) who have persistent disease as determined by MRD methods after intensive chemotherapy.|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Redirected Haploidentical Natural Killer Cell Infusions for B-Lineage Acute Lymphoblastic Leukemia|
|Actual Study Start Date :||September 2013|
|Actual Primary Completion Date :||February 2017|
|Estimated Study Completion Date :||February 2020|
Experimental: anti-CD19 redirected NK cells
This is a single arm study. Intravenous Infusion of activated NK cells bearing anti-CD19-BB-zeta receptors at cell dose of 0.5 - 5 x 10^7 CD56+ cells/kg, and up to 1 x 10^8 CD56+ cells/Kg
Biological: anti-CD19 redirected NK cells
Haploidentical donor NK cells will be expanded and electroporated over 10 days and infused. NK cells will be infused at single dose on day 0. The patient will receive cyclophosphamide 60mg/kg on day - 7 , and Fludarabine 25 mg/m2/day will be given on day -6 to day -2 prior to the NK cell infusion. IL- 2 will be given subcutaneously for 6 doses every alternate day starting on day -1, for NK cell survival.
Other Name: NKCARCD19
- Disease Response Criteria - Minimal Disease Residual (MRD) Monitoring [ Time Frame: 1 Month Post NK Cell Infusion ]Treatment response will be measured by comparing MRD levels before and 1 month after NK cell infusion. Achievement of MRD negativity in bone marrow, i.e., < 0.01% blasts by flow cytometry or PCR, will be regarded as a complete response. Partial response will be defined as ≥ 1 log decrease in MRD levels, while < 1 log decrease in MRD levels will be regarded as no response.
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): NCT01974479
|Department of Paediatrics, National University Health System|
|Singapore, Singapore, 119228|
|Principal Investigator:||Poh Lin Tan||NUHS Singapore|
|Principal Investigator:||Dario Campana||NUHS Singapore|