Clinical Trial of Infusion of Activated NK Cells for the Treatment of Sarcomas (SANKOMA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
|ClinicalTrials.gov Identifier: NCT05952310
Recruitment Status : Recruiting
First Posted : July 19, 2023
Last Update Posted : July 21, 2023
|Condition or disease
|Other: Natural Killer (NK) cells (a new immunotherapy)
Metastatic or relapsed sarcoma in children, adolescents and young adults has a 5-year survival rate of less than 20% and current therapies, consisting of radical surgery and neoadjuvant chemotherapy, are ineffective and new therapeutic strategies are needed.
Natural Killer (NK) cell therapy is a new immunotherapy in development for cancer treatment. We propose a phase I/II clinical trial with the aim of determining the safety and efficacy of infusion of activated and expanded NK cells (NKAE) from a haploidentical donor in children suffering from sarcoma refractory to conventional therapy. The study will be carried out at Hospital Universitario La Paz (Madrid), Hospital Universitario Virgen de la Arrixaca (Murcia) and Hospital Universitario Cruces (Bilbao).
The results of this study are expected to have a direct influence on the approach to metastasis and refractoriness in pediatric solid tumors in future medical therapies.
It is expected to recruit 10 patients who, having received conventional treatment and/or salvage, continue to present metastatic disease or progression. Each patient will receive:
- One cycle of lymphoablative chemotherapy: cyclophosphamide 60 mg/kg iv on day -6 and fludarabine 25 mg/m2/day iv on days -5 to -1.
- Irradiation (2Gy) localized to the tumor and/or its metastases, ideally within 48h prior to NK cell infusion.
- NK cells: Two infusions of cells separated by at least 4 days are established. The first infusion, day 0, will infuse up to 5x107/kg cells with NK and NKT immunophenotype (CD56+CD3- and CD3+). The first infusion will ideally be performed 24-48 h after completion of immunoablative chemotherapy. The second infusion, starting at day +4, up to 5x108/kg, provided that there has been no toxicity attributable to the infusion of the cell product in the previous cycle. In no case will more than 1x107/kg immunophenotype T cells (CD56-CD3+) be infused.
- Cytokine IL-2: Starting on day -1 IL-2 will be administered at a dose of 1x106 IU/m2 subcutaneously every 48 hours, a total of 6 doses.
|Study Type :
|Interventional (Clinical Trial)
|Estimated Enrollment :
|Single Group Assignment
|Intervention Model Description:
|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.
|None (Open Label)
|There is no masking in this study
|Multicenter, Open-label, Phase I/II Clinical Trial of Infusion of Activated NK Cells for the Treatment of Children, Adolescents and Young Adults With Sarcomas
|Actual Study Start Date :
|October 24, 2022
|Estimated Primary Completion Date :
|October 24, 2029
|Estimated Study Completion Date :
|October 24, 2029
Experimental: Allogeneic Natural Killer cells
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)
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.
- Safety of allogeneic haploidentical adult differentiated Natural Killer cell infusion [ Time Frame: Through study completion, an average of 7 years ]
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
- Disease progression [ Time Frame: Five-year after treatment ]Disease progression rate after treatment with Natural Killer (NK) + Inteleukin-2 (IL-2) cells will be determined by imaging techniques.
- Infections (viral, fungal) [ Time Frame: Through study completion, an average of 7 years ]Incidence of episodes of infections (viral, fungal) and hospital admissions associated with treatment.
- Expression levels of Natural Killer cell inhibitory/activating ligands [ Time Frame: Through study completion, an average of 7 years ]Expression levels of Natural Killer (NK) cell inhibitory/activating ligands in solid tumor samples and patient serum. These will be determined by immunohistochemistry and Polymerase Chain Reaction (PCR) techniques.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05952310
|Contact: Antonio Pérez Martínez, PI
|917 27 75 76
|Hospital Universitario La Paz
|Madrid, Spain, 28046
|Contact: Antonio Perez Martinez, PI 917 27 75 76 email@example.com