Malignant SarcomaSANKOMANCT05952310
Clinical Trial of Infusion of Activated NK Cells for the Treatment of Sarcomas
A study testing Natural Killer (NK) cells (a new immunotherapy) in people with Malignant Sarcoma, run by Antonio Pérez Martínez at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Malignant Sarcoma
- What is being tested?
- Natural Killer (NK) cells (a new immunotherapy)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSpain
- Study dates
- 24 Oct 2022to 24 Oct 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
Antonio Perez Martinez, PI, 917 27 75 76, aperezmartinez@salud.madrid.org
About this study
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
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.
Read the 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.
- Conditions
- Malignant Sarcoma
- Being tested
- Natural Killer (NK) cells (a new immunotherapy)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Natural Killer (NK) cells (a new immunotherapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through study completion, an average of 7 years
Secondary outcomes (3)
Disease progression
Disease progression rate after treatment with Natural Killer (NK) + Inteleukin-2 (IL-2) cells will be determined by imaging techniques.
Measured: Five-year after treatment
Infections (viral, fungal)
Incidence of episodes of infections (viral, fungal) and hospital admissions associated with treatment.
Measured: Through study completion, an average of 7 years
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.
Measured: Through study completion, an average of 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2023
- Study start24 Oct 2022
- Primary completion24 Oct 2029 (estimated)
- Study completion24 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Antonio Pérez Martínez
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Antonio Pérez Martínez, Instituto de Investigación Hospital Universitario La Paz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05952310
- Sponsor's protocol ID
- SANKOMA_2016
- Acronym
- SANKOMA
- Status last verified
- Jul 2023
- First submitted
- 11 Jul 2023
- Last updated
- 21 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05952310
- Acronym / sponsor ID
- SANKOMA / SANKOMA_2016
- Conditions
- Malignant Sarcoma
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Antonio Pérez MartínezUniversity, hospital or other
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- 24 Oct 2029 (estimated)
- Study completion
- 24 Oct 2029 (estimated)
- First posted
- 19 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Natural Killer cells | Experimental | Other: Natural Killer (NK) cells (a new immunotherapy)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. |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (9 listed)
- Patients with a history of poor therapeutic compliance.
- Patients who, after a psycho-social evaluation, are censored as unsuitable for the procedure.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Allogeneic Natural Killer cells |
Primary outcome
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
3 secondary outcomes
Disease progression
Time frame: Five-year after treatment
Infections (viral, fungal)
Time frame: Through study completion, an average of 7 years
Expression levels of Natural Killer cell inhibitory/activating ligands
Time frame: Through study completion, an average of 7 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Natural Killer (NK) cells (a new immunotherapy) in people with Malignant Sarcoma, run by Antonio Pérez Martínez at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Antonio Pérez Martínez, PI (917 27 75 76, aperezmartinez@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of allogeneic haploidentical adult differentiated Natural Killer cell infusion (time frame: Through study completion, an average of 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2023.