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Natural Killer Cells in Acute Leukaemia and Myelodysplastic Syndrome

NCT02123836 · Status: UNKNOWN · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 20

Last updated 2019-04-16

No results posted yet for this study

Summary

A novel method has been developed to expand natural (NK) cells and enhance their cytotoxicity against cancer cells while maintaining low killing capacity against non-transformed cells. In this method, donor NK cells are expanded by co-culture with the irradiated K562 cell line modified to express membrane bound IL-15 and 41BB ligand (K562-mb15-41BBL). Expression of these proteins in conjunction with unknown stimuli provided by K562 cells promotes selective growth of NK cells. Then, the expanded NK cell population is depleted of T cells to prevent graft versus host disease (GVHD). Expanded and activated NK cells showed powerful anti-leukemic activity against acute myeloid leukemia (AML) cells in vitro and in animal models of leukemia.Unpublished laboratory results also demonstrated that T-cell acute lymphoblastic leukaemia (T-ALL) is extremely sensitive to the cytotoxicity exerted by the expanded and activated NK cells.

The present study represents the translation of the laboratory findings into clinical application. The study proposes to determine the feasibility, safety and efficacy of infusing expanded NK cells into patients who have AML or T-lineage ALL which is resistant to standard therapy as demonstrated by persistent minimal residual disease (MRD). Patients with myelodysplastic syndrome (MDS), who are at high risk to develop AML will also be eligible for the study. In this patient cohort, the study will also investigate the in vivo lifespan and phenotype of the expanded NK cells.

The main hypothesis to be tested in this study is that infusion of expanded activated NK cells can produce measurable clinical responses in patients with AML or T-ALL.

Conditions

Interventions

BIOLOGICAL

NK cells

7 days of preparatory treatment are given before the NK cell infusion. Chemotherapy will be given over 6 days. This chemotherapy will promote donor NK cells engraftment. After which, a drug called Interleukin-2 (IL-2) will be given as an injection just under the skin three times per week for at least 2 weeks (total of 6 doses). This treatment is used to help keep the donor NK cells alive. Blood cells will be collected from an eligible and suitable family donor 10 days before infusion. The collection sample will be processed to remove red blood cells and as many T-cells as possible. T-cells from the donor might cause these donor cells to attack the body, usually the skin, liver, and intestines. NK cells will be activated in the National University Hospital lab and ready for infusion on Day 0. The NK cells will then be infused into the vein, through a peripheral catheter.

Sponsors & Collaborators

  • National University Hospital, Singapore

    lead OTHER

Principal Investigators

  • Frances Yeap, MBBS · National University Hospital, Singapore

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
6 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-04-30
Primary Completion
2020-09-30
Completion
2020-10-31

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 NCT02123836 on ClinicalTrials.gov