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

NCT01974479 · Status: SUSPENDED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 20

Last updated 2019-04-12

No results posted yet for this study

Summary

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.

Conditions

Interventions

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.

Sponsors & Collaborators

  • National University Health System, Singapore

    lead OTHER

Principal Investigators

  • Poh Lin Tan · NUHS Singapore

  • Dario Campana · NUHS Singapore

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-09-30
Primary Completion
2017-02-28
Completion
2020-02-29

Countries

  • Singapore

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01974479 on ClinicalTrials.gov