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Clinical Trial of Infusion of Activated NK Cells for the Treatment of Sarcomas (SANKOMA)

Primary Purpose

Malignant Sarcoma

Status
Recruiting
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Natural Killer (NK) cells (a new immunotherapy)
Sponsored by
Antonio Pérez Martínez
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Sarcoma

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. 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. Presence of a compatible haploidentical donor (father or mother or sibling). Exclusion Criteria: 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. Subjects who have been administered other investigational drugs in the 90 days prior to inclusion.

Sites / Locations

  • Hospital Universitario La PazRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic Natural Killer cells

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Disease progression
Disease progression rate after treatment with Natural Killer (NK) + Inteleukin-2 (IL-2) cells will be determined by imaging techniques.
Infections (viral, fungal)
Incidence of episodes of infections (viral, fungal) and hospital admissions associated with treatment.
Expression levels of Natural Killer cell inhibitory/activating ligands
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.

Full Information

First Posted
July 11, 2023
Last Updated
July 19, 2023
Sponsor
Antonio Pérez Martínez
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1. Study Identification

Unique Protocol Identification Number
NCT05952310
Brief Title
Clinical Trial of Infusion of Activated NK Cells for the Treatment of Sarcomas
Acronym
SANKOMA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2022 (Actual)
Primary Completion Date
October 24, 2029 (Anticipated)
Study Completion Date
October 24, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Antonio Pérez Martínez

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Masking Description
There is no masking in this study
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Natural Killer cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Natural Killer (NK) cells (a new immunotherapy)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety of allogeneic haploidentical adult differentiated Natural Killer cell infusion
Description
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
Time Frame
Through study completion, an average of 7 years
Secondary Outcome Measure Information:
Title
Disease progression
Description
Disease progression rate after treatment with Natural Killer (NK) + Inteleukin-2 (IL-2) cells will be determined by imaging techniques.
Time Frame
Five-year after treatment
Title
Infections (viral, fungal)
Description
Incidence of episodes of infections (viral, fungal) and hospital admissions associated with treatment.
Time Frame
Through study completion, an average of 7 years
Title
Expression levels of Natural Killer cell inhibitory/activating ligands
Description
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.
Time Frame
Through study completion, an average of 7 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Presence of a compatible haploidentical donor (father or mother or sibling). Exclusion Criteria: 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. Subjects who have been administered other investigational drugs in the 90 days prior to inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio Pérez Martínez, PI
Phone
917 27 75 76
Email
aperezmartinez@salud.madrid.org
Facility Information:
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Perez Martinez, PI
Phone
917 27 75 76
Email
aperezmartinez@salud.madrid.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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