Clinical Trial of Infusion of Activated NK Cells for the Treatment of Sarcomas

NCT05952310 | Recruiting

• 1 other identifier: SANKOMA_2016
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Disease progression

  Five-year after treatment

• Infections (viral, fungal)

  Through study completion, an average of 7 years

• Expression levels of Natural Killer cell inhibitory/activating ligands

  Through study completion, an average of 7 years

Study Arms (1)

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.

Other: Natural Killer (NK) cells (a new immunotherapy)

Interventions

Natural Killer (NK) cells (a new immunotherapy) OTHER

It is proposed to infuse allogeneic NK cells from a haploidentical donor, after administration of lymphoablative chemotherapy and/or radiotherapy, as a treatment in patients with sarcomas, who have completed conventional treatment but maintain detectable residual disease. The administration of low doses of radiotherapy is aimed at stressing residual tumor cells by increasing the expression of NK cell activating receptor ligands. The administration of prior chemotherapy aims at immunosuppressing the patient, allowing immunotherapy with allogeneic NK cells from haploidentical donor as well as autologous NK cell recovery to lead the immune reconstitution after chemotherapy, prolonging the antitumor effect. In conjunction with NK cell infusion, low doses (1x106/UI/m2) of interleukin 2 (IL-2) will be administered subcutaneously every 48h for a maximum of 6 doses, to favor the expansion and antitumor effect of NK cells.

Allogeneic Natural Killer cells

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• Lansky/Karnofsky index \> 60%.
• Mild-moderate (\<4) organ functional impairment (hepatic, renal, respiratory), according to National Cancer Institute criteria (NCI CTCAE v5.0).
• Left ventricular ejection fraction \>39%.
• Adult subjects who voluntarily signed informed consent prior to the first study intervention.
• Minor subjects whose representative/legal guardian voluntarily signed the informed consent prior to the first intervention of the study.
• 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.
• Presence of a compatible haploidentical donor (father or mother or sibling).

You may not qualify if:

• Patients with a history of poor therapeutic compliance.
• 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.
• Severe functional organ impairment (hepatic, renal, respiratory) (4), according to the criteria of the National Cancer Institute (NCI CTCAE 5.0).
• Contraindications, interactions, precautions for use and dose reductions indicated in the corresponding data sheets must be considered.

Sponsors & Collaborators

• Antonio Pérez Martínez: lead

Study Sites (1)

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

MeSH Terms

Interventions

Cell Count

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Central Study Contacts

Antonio Pérez Martínez, PI

CONTACT

917 27 75 76; aperezmartinez@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: There is no masking in this study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of Pediatric Hemato-Oncology and Hematopoietic Transplantation Service

Model Details: This is an exploratory, open-label, non-randomized, multicenter therapeutic study. It is considered phase I/II since it will seek safety and efficacy of the infusion of allogeneic haploidentical Natural Killer (NK) cells in combination with chemotherapy and/or radiotherapy in the treatment of pediatric, adolescent and young adult patients with refractory sarcoma.

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: July 19, 2023
• Study Start: October 24, 2022
• Primary Completion (Estimated): October 24, 2029
• Study Completion (Estimated): October 24, 2029
• Last Updated: July 21, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)