Clinical trial · Interventional
Natural Killer Cells in Acute Leukaemia and Myelodysplastic Syndrome
Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Acute Leukaemia and Myelodysplastic Syndrome
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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Unpublished laboratory results also demonstrated that T-cell acute lymphoblastic leukaemia (T-ALL) is extremely sensitive to the cytotoxicity exerted by the expanded and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
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Leukaemia | Acute Leukemia | ONTOLOGY_EXACT | 0.90 |
| Myelodysplastic Syndrome | Myelodysplastic Syndrome | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| NK cells | Biological | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- NK cells
- description
- Peripheral blood cell will be collected by apheresis from donors. Peripheral blood mononucleated cells will be cultured with irradiated K562-mb15-41BBL cells and low dose (10 IU/mL) IL-2 for 10 days. After T-cell depletion, expanded activated NK cells will be infused. Before infusion, patients will receive immunosuppressive therapy to promote temporary engraftment of NK cells. After infusion, they will receive IL-2 to support NK cell viability and expansion in vivo. The effects of NK cell infusion will be determine by comparing MRD levels before and after treatment.
- interventionNames
- Biological: NK cells
Primary outcomes (1)
- measure
- Minimal Residual Disease (MRD) levels
- timeFrame
- 1 year
- description
- MRD blood levels will be tested at baseline, weekly during the first 2 months and monthly thereafter
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 6 Years
- Maximum age
- 80 Years
Show eligibility criteria text
Inclusion Criteria: (NK cell Recipient) * From 6 to 80 years old at time of consent. * Patients with the following haematological diseases: * Acute myeloid leukaemia (de novo or secondary) * Myelodysplastic syndromes (RAEB I/II) * T-cell acute lymphoblastic leukaemia (T-ALL) * Patients must have been treated with prior standard intensive chemotherapy upfront, which will be defined according to institutional practice for each respective disease, and may include allogeneic haematopoietic stem cell transplantation. * Patients must have persistent detectable residual leukaemia following initial treatment with intensive chemotherapy. Residual leukaemia is defined as the presence of \>=0.01%-20% blasts in the bone marrow by flow cytometry. * High risk AML patients with either High risk cytogenetics or FLT3-ITD mutation or Acute megakaryoblastic leukaemia in non-Down's Therapy related leukaemia or Myelodysplastic syndrome will qualify for NKEXPSIN either after Induction I chemotherapy or Induction II chemotherapy regardless of residual disease. * At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy. * Shortening fraction greater than or equal to 25%. * Glomerular filtration rate greater than or equal to 60ml/min. * Pulse oximetry greater than or equal to 92% on room air. * Direct bilirubin less than or equal to 3x Upper Limit of Normal (ULN). * Karnofsky performance score of greater than or equal to 50. * Has a suitable adult family member donor available for NK cell donation. * Ability to provide informed consent. Otherwise, a legally authorized representative (LAR) must be present throughout the consent process and is allowed to give consent on the patient's behalf. Inclusion Criteria: (NK cell Donor) * At least 21 years old at time of consent. * A family member with a greater than or equal to 3 of 6 HLA match to recipient * Ability to provide informed consent. Otherwise, a legally authorized representative must be present throughout the consent process and is allowed to give consent on the patient's behalf. Exclusion Criteria: (NK cell Recipient) * Currently has pleural or pericardial effusion. * Receiving more than the equivalent of prednisone 10 mg daily. * Lactating or pregnant. Negative serum or urine pregnancy test result must be within 7 days prior to enrolment. Exclusion Criteria: (NK cell Donor) * HIV positive. Negative results must be within 60 days prior to enrolment. * Lactating or pregnant. Negative serum or urine pregnancy test result must be within 7 days prior to enrolment.
References
Publications (3)
- BACKGROUNDFujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T, Eldridge P, Leung WH, Campana D. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009 May 1;69(9):4010-7. doi: 10.1158/0008-5472.CAN-08-3712. Epub 2009 Apr 21. PMID 19383914
- BACKGROUNDImai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005 Jul 1;106(1):376-83. doi: 10.1182/blood-2004-12-4797. Epub 2005 Mar 8. PMID 15755898
- BACKGROUNDFujisaki H, Kakuda H, Imai C, Mullighan CG, Campana D. Replicative potential of human natural killer cells. Br J Haematol. 2009 Jun;145(5):606-13. doi: 10.1111/j.1365-2141.2009.07667.x. Epub 2009 Mar 26. PMID 19344420