CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Patients aged between 0 and 30 years diagnosed with malignant sarcoma, who at the end of conventional treatment still have detectable residual disease (based on imaging techniques) or in case of stable disease or minimal disease when there is an absence of clinical benefit from chemotherapy (poor tolerance due to adverse effects related to chemotherapy).
2. Lansky/Karnofsky index \> 60%.
3. Mild-moderate (\<4) organ functional impairment (hepatic, renal, respiratory), according to National Cancer Institute criteria (NCI CTCAE v5.0).
4. Left ventricular ejection fraction \>39%.
5. Adult subjects who voluntarily signed informed consent prior to the first study intervention.
6. Minor subjects whose representative/legal guardian voluntarily signed the informed consent prior to the first intervention of the study.
7. In the case of mature minors (12 - 17 years of age), in addition to the consent signed by the legal guardian, the minor's assent will be obtained.
8. Women of childbearing capacity must have a negative pregnancy test at the time of inclusion and must agree to use highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, oral contraceptive combined with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence or partner with vasectomy) during their participation in the study and within 30 days of the last visit.
9. Presence of a compatible haploidentical donor (father or mother or sibling).

Exclusion Criteria:

1. Patients with a history of poor therapeutic compliance.
2. Patients who, after a psycho-social evaluation, are censored as unsuitable for the procedure.

   * Socio-familial situation that makes proper participation in the study impossible.
   * Patients with emotional or psychological problems secondary to the disease, such as post-traumatic stress disorder, phobias, delirium, psychosis, requiring specialist support.
   * Evaluation of the involvement of family members in the patient's health.
   * Impossibility to understand information about the trial.
3. Severe functional organ impairment (hepatic, renal, respiratory) (4), according to the criteria of the National Cancer Institute (NCI CTCAE 5.0).
4. Contraindications, interactions, precautions for use and dose reductions indicated in the corresponding data sheets must be considered.
5. Subjects who have been administered other investigational drugs in the 90 days prior to inclusion.

主要终点：Safety of allogeneic haploidentical adult differentiated Natural Killer cell infusion · Safety of infusion of allogeneic haploidentical adult differentiated Natural Killers cells in combination with inteleukin-2 after chemotherapy and radiotherapy. Each patient will be monitored for the detection of possible adverse effects. The Common Terminology Criteria for Adverse Events V5.0 will be followed and the proportion of patients with toxicity will be determined according to the degree of toxicity. The intensity of toxic effects that cannot be classified according to the criteria for toxicity of the aforementioned system will be classified as follows (MedDRA classification): (a) Mild (asymptomatic); b) Moderate (symptomatic but does not significantly interfere with function); c) Severe (causes significant interference with function); d) Life-threatening · Through study completion, an average of 7 years
次要终点：Disease progression；Infections (viral, fungal)；Expression levels of Natural Killer cell inhibitory/activating ligands

• Allogeneic Natural Killer cells · EXPERIMENTAL · Low doses (1x106/UI/m2) of subcutaneous interleukin-2 (IL-2) will be administered every 48h for a maximum of 6 doses, in conjunction with the NK cell infusion, to favor the expansion and antitumor effect of the NK cells.

This is an exploratory therapeutic study (according to the terminology of the "ICH Harmonised Tripartite Guideline Topic E8. General Considerations for Clinical Trials". EMEA, March 1998. CPMP/ICH/291/95), open-label, non-randomized, multicenter study. It is considered phase I/II since the safety and efficacy of the infusion of allogeneic haploidentical NK cells in combination with chemotherapy and/or radiotherapy in the treatment of pediatric, adolescent and young adult patients with refractory sarcoma will be sought.