Acute lymphoblastic leukemia (ALL) Acute myeloid leukemia (AML) Allogeneic stem cell transplantation
Conditions
Interventions
Patients will receive one infusion of 5-10x10e6 ex vivo IL-15-activated donor NK cells per kg body weight (maximum dose: 200x10e6) at 4-12 weeks after transplantation.
Sponsors
Leiden University Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: - Aged between 1-18 years at the time of hematopietic stem cell tranplantation (HSCT) - Undergoing HSCT for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) according to existing indications - Receiving a stem cell graft from a mismatched family or volunteer unrelated donor - Life expectancy>3 months - Availability of a stem cell donor willing to donate white blood cells by means of a non-mobilized leukapheresis procedure
Exclusion criteria
Exclusion criteria: - Progressive uncontrollable malignant disease after HSCT but before or at the day of NK cell infusion, defined as overt leukemia relapse, i.e., ¡Ý 25% blasts in the marrow and/or 5% circulating blasts in the peripheral blood or progressive extra-medullary disease - Lack of evidence for donor myeloid engraftment at the day of infusion (1 mg/kg/day for any indication at the day of infusion - Any medical condition, which in the opinion of the treating physician, would interfere with the adequate evaluation of the patient (e.g. end-stage irreversible multi-system organ failure) - Cord blood stem cell donor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| In addition to the standard evaluation following HSCT of children treated for leukemia, the following investigations will be performed in the context of the investigational NK cell infusion: - To determine the number of patients for whom an investigational medicinal product (IMP), meeting all release criteria, can be generated. The protocol is considered feasible if: > 50 % of transplanted patients can be included > 66 % of included patients can be infused with the IMP. - Registration of post infusion status of the patient, fever, nausea, chills, rash, erythema, and all serious adverse events, potentially linked to infusion. The IMP is considered safe and well-tolerated if no more than 2 out of 12 patients develop severe adverse reactions that are likely due to the NK cell infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| - The anti-leukemic/cytolytic reactivity and cytokine producing potential, e.g. IFN-ã, of NK cells ex vivo prior to and after NK infusion (intra-individual control) - Immune reconstitution after NK cell infusion. Apart from detailed investigation of T- and B-lymphocyte recovery, the focus will be on analysis of the surface expression patterns of activating and inhibitory receptors on NK cell subpopulations. The latter will also be investigated on NK cells present in the donor HSCT graft (if not CD34+ enriched), donor leukapheresis material and the IMP. Patients who will not be included in this study for logistic reasons as well as matched historic controls will be used for the functional and phenotypical studies indicated above - The incidence of disseminated (viral) infections in children undergoing NK cell infusions post-HSCT compared to aforementioned controls - The occurrence and severity of acute and chronic GvHD in NK cell recipients compared to aforementioned controls - The incidence of relapses of leukemia in children undergoing NK cell infusions post HSCT compared to controls. - Survival in children undergoing NK cell infusions post-HSCT compared to controls. - The relevance of mismatching KIR ligands (HLA types) and KIR genotype/phenotype of donor/recipient pairs for observed biological effects | — |
Contacts
Public ContactM.W. Schilham
Pediatric Immunology Laboratory Department of Pediatrics Leiden University Medical Center Albinusdreef 2
Outcome results
None listed