Clinical trial · Interventional
NK Cells as Consolidation Therapy of Acute Myeloid Leukemia in Children/Adolescents
NK Cells Infusion as Consolidation Treatment of Acute Myeloid Leukemia in Children and Adolescents
NCT02763475CI-TRIAL-00047490completedPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- 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)
The main goal of this study is to evaluate the anti-relapse prophylactic activity of inoculating Natural Killer (NK) cells as consolidation therapy of acute myeloid leukemia in paediatric patients with cytologic remission. The patients included have intermediate risk of relapse and no indication for allogeneic hematopoietic stem cell transplantation. After the standard induction and consolidation chemotherapy treatment, patients will receive five days of fludarabine to try to kill any minimal residual disease and prevent NK cell rejection. Two different NK cells infusions will be performed within one week (day 0 and 7). Interleukin 2 (IL-2) will be administrated to increase the cytotoxic activity of NK cells.
Conditions
Conditions (3)
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 Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
| Myeloid Leukemia | Myeloid Leukemia | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Fludarabine | Drug | Fludarabine | ALIAS |
| IL-2 | Drug | — | UNRESOLVED |
| NK cell infusion | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Natural Killer (NK) Cells + Chemotherapy
- description
- Starting on day -6, 60mg/Kg cyclophosphamide by vein will be administrated. Day -5 to -1 fludarabine administrated by vein at 25 mg/m2. 24-48 hours after chemotherapy completion, NK cell infusion will be injected (day 0). On day 7 a second NK cell infusion will be administrated. First infusion consist of 5x10\^7/kg NK CD3-CD56+ NK cells. The second NK cell infusion will include up to 5x10\^8 CD3-CD56+ cells if no treatment related toxicity occurred. Subcutaneous IL-2 (1x10\^6 UI/m2) three times a week for two weeks will be administrated after first NK infusion.
- interventionNames
- Drug: cyclophosphamide
- Drug: Fludarabine
- Procedure: NK cell infusion
- Drug: IL-2
Primary outcomes (4)
- measure
- Relapse-free rate after allogeneic haploidentical NK cell infusion
- timeFrame
- Relapse-free rate at 1 month
- description
- Relapse-free rate according to the clinical guidelines. A bone narrow aspirate one month after NK cell infusion will be evaluated for cytomorphological criteria and minimal residue disease (cytometry or real time PCR). Relapse defined as myeloid blast bone marrow presence with the same diagnosis markers, new ones or mixed. From cytologic analysis 25% of blast or minimal residue disease by cytometry (0,01%) and/or molecular level (0,0001%) present at diagnosis with or without cytogenetic alterations.
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 21 Years
Show eligibility criteria text
Inclusion Criteria: 1. Patients aged between 0 and 21 years, diagnosed with AML in first cytological remission who have completed the induction and consolidation chemotherapy phases and no criteria for allogeneic hematopoietic stem cell transplantation (HSCT), ie patients who have responded well to induction lacking donor HLA identical relative and do not have high-risk cytogenetic abnormalities. 2. Karnofsky or Lansky Performance Scale (PS) \> 60% 3. Mild-moderate (\<4) organ functional impairment (liver, kidney, respiratory) according to the criteria of the National Cancer Institute (NCI CTCAE v4). 4. Left ventricular ejection fraction\> 39% 5. Adult subjects who have voluntarily signed informed consent before the first study intervention. 6. Minor subjects whose representative / legal guardian has voluntarily signed informed consent before the first study intervention. 7. For mature minors (12 to 17 years old), in addition to the consent signed by the legal guardian, the assent of the child will be obtained. 8. Women of childbearing potential must have a negative pregnancy test at the time inclusion and must agree to use highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, combined oral contraceptive with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence or partner with vasectomy) while participating in the study and 30 days after the last visit. 9. Presence of a haploidentical donor Exclusion Criteria: 1. Patients with a history of poor treatment compliance 2. Patients who after a psycho-social assessment are censored as unfit for procedure: * Socio-familiar situation that precludes proper participation in the study. * Patients with emotional or psychological problems secondary to the illness such as PTSD, phobias, delusions, psychosis, requiring assistance by specialists. * Evaluation of the involvement of the family in the patient's health. * Inability to understand the information about the trial. 3. Severe (4) organ functional impairment (liver, kidney, respiratory) according to the criteria of the National Cancer Institute (NCI CTCAE v4). 4. They should be considered contraindications, interactions, precautions for use and dose reductions indicated in the respective data sheets. 5. Subjects who have been administered other investigational drugs within 90 days prior to inclusion
References
Publications (3)
- BACKGROUNDBlomberg K, Granberg C, Hemmila I, Lovgren T. Europium-labelled target cells in an assay of natural killer cell activity. II. A novel non-radioactive method based on time-resolved fluorescence. significance and specificity of the method. J Immunol Methods. 1986 Aug 21;92(1):117-23. doi: 10.1016/0022-1759(86)90511-9. PMID 3745921
- DERIVEDGomez Garcia LM, Escudero A, Mestre C, Fuster Soler JL, Martinez AP, Vagace Valero JM, Vela M, Ruz B, Navarro A, Fernandez L, Fernandez A, Leivas A, Martinez-Lopez J, Ferreras C, De Paz R, Blanquer M, Galan V, Gonzalez B, Corral D, Sisinni L, Mirones I, Balas A, Vicario JL, Valle P, Borobia AM, Perez-Martinez A. Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL-Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2021 May;21(5):328-337.e1. doi: 10.1016/j.clml.2021.01.013. Epub 2021 Jan 25. PMID 33610500
- DERIVEDMunoz Builes M, Vela Cuenca M, Fuster Soler JL, Astigarraga I, Pascual Martinez A, Vagace Valero JM, Tong HY, Valentin Quiroga J, Fernandez Casanova L, Escudero Lopez A, Sisinni L, Blanquer M, Mirones Aguilar I, Gonzalez Martinez B, Borobia AM, Perez-Martinez A. Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic activated and expanded natural killer cells as consolidation therapy for paediatric acute myeloblastic leukaemia. BMJ Open. 2020 Jan 8;10(1):e029642. doi: 10.1136/bmjopen-2019-029642. PMID 31919123