Pediatric CancerPhase 1NCT04400851
Sintilimab in the Treatment of Advanced and Refractory Pediatric Malignant Tumors
A Phase 1 study testing Sintilimab in people with Pediatric Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
This is a single center, single arm, open-label and phase I clinical study. The standard 3 + 3 group design was performed. Patients were enrolled by the design of phase I study standard. Sintilimab was divided into three dose levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Pediatric Cancer
- What is being tested?
- Sintilimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 11 Aug 2020to 10 Dec 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: 1-18 years old;
- ECOG PS score: 0-1;
- Pediatric malignant tumors confirmed by histopathology include Hodgkin's lymphoma, mediastinal large B-cell lymphoma, NK / T-cell lymphoma, nasopharyngeal carcinoma, malignant melanoma, neuroblastoma, hepatoblastoma, sarcoma, brain tumor, etc;
- Late stage patients who failed to receive standard treatment;
- There must be at least one measurable lesion defined by RECIST or who standard;
- Estimated survival time ≥ 6 months;
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- Heart function:
- LVEF ≥ 50% by color Doppler echocardiography;
- EKG showed no myocardial ischemia;
- There was no history of arrhythmia requiring drug intervention before admission;
- Patients must fully recover from the acute toxicity of all previous anticancer chemotherapy;
- Myelosuppression chemotherapy: at least 21 days after the last myelosuppression chemotherapy (42 days if nitrosourea was used in the earlier stage);
- Experimental drug or anti-cancer therapy other than chemotherapy: it can not be used within the first 28 days before the planned start of the use of sintilimab, and must be clearly recovered from the clinically significant toxicity of the therapy;
- Immunotherapy: at least 42 days after completion of any type of immunotherapy (excluding steroids), including immunocheckpoint inhibitors and tumor vaccines;
- X-ray therapy (XRT): at least 14 days after local palliative XRT (small oral area); in case of other substantial bone marrow (BM) irradiation, including pre radioiodinated m-iodobenzidine (131I-MIBG) treatment, at least 42 days must be ended;
- Stem cell infusion without total body irradiation (TBI): there is no evidence of active graft-versus-host disease. At least 56 days must elapse after transplantation or stem cell infusion;
- Patients who have previously received CTLA-4 antibody must meet the following conditions to be admitted to the group
- More than 12 weeks after the last administration; b）No history of serious immune related adverse events (CTCAE V4.03 G3 or G4);
- For patients with known no BM involvement:
- Neutrophil absolute count (ANC) ≥ One ×109/L；
- Platelet count ≥ one hundred ×109/L；
- Hemoglobin ≥ 90 g / L;
- Liver and kidney function should meet the following standards:
- Bilirubin (combined + unconjugated sum) ≤ Two point five * upper limit of normal value (ULN) (corresponding to age), patients who have been confirmed as Gilbert's syndrome can be judged according to the researchers;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ Two point five ×ULN；
- Estimated glomerular filtration rate ≥ 30 ml / min/ one point seven three M2 or serum creatinine (CR) ≤ One point five ×ULN；
- During the period of participating in the study, be able to follow the outpatient treatment, laboratory monitoring and necessary clinical visits;
- The parents / guardians of the child or adolescent subjects have the ability to understand, agree and sign the study informed consent form (ICF) and the applicable child consent form before initiating any program related procedures; the subjects have the ability to express their consent (when applicable) with the consent of the parents / guardians.
Who cannot join
- Received anti-PD-1 or anti-PD-L1 monoclonal antibody or related pathway targeted drugs;
- Known to be allergic to PD-1 monoclonal antibody or any of its adjuvants; known to have a history of allergic diseases or severe allergic constitution;
- Patients with other malignant tumor diseases other than those treated by the Institute, except for patients who has been cured and with no recurrence within 3 years before the study was selected, completely removed basal cell and squamous cell skin cancer, completely removed any type of carcinoma in situ;
- Active central nervous system metastasis (whether or not treated), including symptomatic brain metastasis or meningeal metastasis or spinal cord compression, etc.; except: asymptomatic brain metastasis (no progress within at least 4 weeks after radiotherapy and / or no neurological symptoms or signs after surgical resection, no need for dexamethasone or mannitol treatment).
- Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
- The toxicity of previous treatment is still more than grade 1 (CTCAE V4.03 Standard), except hair loss and neurotoxicity;
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- Having a history of mental disorders;
- Those who have a history of drug use or drug abuse upon inquiry;
- History of idiopathic pulmonary fibrosis or pneumonia;
- The complications that need to be treated with immunosuppressive drugs, or the complications that need to be treated with systemic or local corticosteroids according to the dose with immunosuppressive effect (prednisone > 10 mg / day or equivalent dose of similar drugs).
- Have a history of autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., except for: type I diabetes, hypothyroidism that can be controlled only through hormone replacement therapy, skin diseases that do not need systemic treatment (such as vitiligo, psoriasis), controlled celiac disease, or Disease that does not recur without external stimulus;
- Patients with active TB infection before or now;
- Active infection requiring systemic treatment;
- Uncontrolled hypertension (systolic ≥ 140 mmHg and / or diastolic ≥ 90 MmHg) or pulmonary hypertension or unstable angina pectoris; myocardial infarction or bypass or stent operation within 6 months before administration; history of chronic heart failure meeting NYHA level 3-4; valvular disease of clinical significance; serious arrhythmia requiring treatment (excluding atrial fibrillation and paroxysmal supraventricular tachycardia), including QTc interval male ≥ 450ms , female ≥ 470ms (calculated by friderica formula), cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months before administration, etc;
- Serious medical diseases, including but not limited to: uncontrolled diabetes, active peptic ulcer, active bleeding, etc;
- Anti HIV, TP AB and HCV AB were positive, HBV AG was positive and HBV DNA copy number was higher than the upper limit of normal value of detection unit;
- Thyroid function was abnormal (FT3, FT4, T3, T4);
- Major surgery is expected within 28 days before administration or during treatment;
- Live vaccine or attenuated vaccine is expected to be given 4 weeks before administration, during treatment or within 5 months after the last administration;
- Participate in another clinical trial and receive the trial drug treatment within 30 days before administration;
- According to the judgment of the investigator, patients who are not suitable for the trial due to other reasons.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Yizhuo Zhang
Guangzhou
Yizhuo Zhang, 020-87342459, zhangyzh@sysucc.org.cn
About this study
Official title: Sintilimab in the Treatment of Advanced and Refractory Pediatric Malignant Tumors-A Phase I Study
This is a single center, single arm, open-label and phase I clinical study. The standard 3 + 3 group design was performed. Patients were enrolled by the design of phase I study standard. Sintilimab was divided into three dose levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. Dose escalation was carried out from the first level of sintilimab. The study is to evaluate the safety, including dose limited toxicity (DLT) in the treatment of advanced, recurrent, and refractory childhood cancer.
Read the detailed description
Malignant tumors are the second leading cause of death in China after accidental casualties, which is consistent with developed countries in Europe and America.
Sintilimab is a human monoclonal antibody against PD-1 receptor which was developed in China. It can block the binding of PD-1 of T-lymphocyte and PD-L1 on the surface of tumor cells, release the immunosuppression of tumor cells on immune cells, making immune cells play the role of anti-tumor cell immunity again and kill tumor cells. In the past, the development of immunocheckpoint drugs mainly focused on adult cancer. Immunocheckpoint inhibition has achieved many successes in the adult population, including metastatic melanoma, non-small cell lung cancer, Hodgkin's lymphoma, bladder cancer and head and neck cancer.
In the past, the development of immunocheckpoint drugs mainly focused on adult cancer. Immunocheckpoint inhibition has achieved many successes in adult population. However, some results of the clinical trials of immunocheckpoint inhibitors in children are also promising especially in Hodgkin's lymphoma.
The investigators aimed to determine the maximum tolerable dose and effectiveness in pediatric malignant tumors, so as to lay the foundation for the future phase II / III clinical research.
- Conditions
- Pediatric Cancer
- Being tested
- Sintilimab
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SintilimabDrug
Patients were enrolled by the design of phase I study standard. Sintilimab was divided into three dosage levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. The first level of sintilimab was followed by dose escalation
| Study group | Role | What they receive |
|---|---|---|
| Sintilimab in advanced childhood cancer patients | Experimental | Not described Receives: Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerable dose (MTD)
Determine the appropriate dose of maximum tolerable dose (MTD) of sintilimab for further clinical study in this patient population
Measured: From date of enrollment until the end of 1 cycle of treatment, assessed up to 3 weeks
Secondary outcomes (2)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Hematology and non-hematology toxicity (NCI CTCAE v5.0 )
Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
Objective presponse rate (ORR)
complete release and partial release
Measured: From the date of the treatment to the first evaluation (After 2 cycles of treatment assessed up to 6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start11 Aug 2020
- Primary completion10 Oct 2021 (estimated)
- Study completion10 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pediatric CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Responsible party
- Principal investigator, Yizhuo Zhang, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04400851
- Sponsor's protocol ID
- SunYat-sen-Sintilimab
- Status last verified
- Sep 2020
- First submitted
- 19 May 2020
- Last updated
- 3 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Que Y, Wang J, Sun F, Wang S, Zhu J, Huang J, Zhao Z, Zhang L, Liu J, Xu J, Zhen Z, Sun X, Lu S, Zhang Y. Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study. Signal Transduct Target Ther. 2023 Oct 13;8(1):392. doi: 10.1038/s41392-023-01636-9.
PubMed 37828033
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sintilimab in the Treatment of Advanced and Refractory Pediatric Malignant Tumors-A Phase I Study
- ClinicalTrials.gov ID
- NCT04400851
- Acronym / sponsor ID
- SunYat-sen-Sintilimab
- Conditions
- Pediatric Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Study start
- 11 Aug 2020 (actual)
- Primary completion
- 10 Oct 2021 (estimated)
- Study completion
- 10 Dec 2021 (estimated)
- First posted
- 26 May 2020 (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 a single center, single arm, open-label and phase I clinical study. The standard 3 + 3 group design was performed. Patients were enrolled by the design of phase I study standard. Sintilimab was divided into three dose levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. Dose escalation was carried out from the first level of sintilimab. The study is to evaluate the safety, including dose limited toxicity (DLT) in the treatment of advanced, recurrent, and refractory childhood cancer.
Detailed description
Malignant tumors are the second leading cause of death in China after accidental casualties, which is consistent with developed countries in Europe and America.
Sintilimab is a human monoclonal antibody against PD-1 receptor which was developed in China. It can block the binding of PD-1 of T-lymphocyte and PD-L1 on the surface of tumor cells, release the immunosuppression of tumor cells on immune cells, making immune cells play the role of anti-tumor cell immunity again and kill tumor cells. In the past, the development of immunocheckpoint drugs mainly focused on adult cancer. Immunocheckpoint inhibition has achieved many successes in the adult population, including metastatic melanoma, non-small cell lung cancer, Hodgkin's lymphoma, bladder cancer and head and neck cancer.
In the past, the development of immunocheckpoint drugs mainly focused on adult cancer. Immunocheckpoint inhibition has achieved many successes in adult population. However, some results of the clinical trials of immunocheckpoint inhibitors in children are also promising especially in Hodgkin's lymphoma.
The investigators aimed to determine the maximum tolerable dose and effectiveness in pediatric malignant tumors, so as to lay the foundation for the future phase II / III clinical research.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sintilimab in advanced childhood cancer patients | Experimental | Drug: Sintilimab |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Age: 1-18 years old;
- ECOG PS score: 0-1;
- Pediatric malignant tumors confirmed by histopathology include Hodgkin's lymphoma, mediastinal large B-cell lymphoma, NK / T-cell lymphoma, nasopharyngeal carcinoma, malignant melanoma, neuroblastoma, hepatoblastoma, sarcoma, brain tumor, etc;
- Late stage patients who failed to receive standard treatment;
- There must be at least one measurable lesion defined by RECIST or who standard;
Key exclusion criteria (21 listed)
- Received anti-PD-1 or anti-PD-L1 monoclonal antibody or related pathway targeted drugs;
- Known to be allergic to PD-1 monoclonal antibody or any of its adjuvants; known to have a history of allergic diseases or severe allergic constitution;
- Patients with other malignant tumor diseases other than those treated by the Institute, except for patients who has been cured and with no recurrence within 3 years before the study was selected, completely removed basal cell and squamous cell skin cancer, completely removed any type of carcinoma in situ;
- Active central nervous system metastasis (whether or not treated), including symptomatic brain metastasis or meningeal metastasis or spinal cord compression, etc.; except: asymptomatic brain metastasis (no progress within at least 4 weeks after radiotherapy and / or no neurological symptoms or signs after surgical resection, no need for dexamethasone or mannitol treatment).
- Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
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 |
|---|---|---|
| SintilimabPatients were enrolled by the design of phase I study standard. Sintilimab was divided into three dosage levels: 1 mg / kg, 3 mg / kg, and 10 mg / kg. The first level of sintilimab was followed by dose escalation | Drug | Sintilimab in advanced childhood cancer patients |
Primary outcome
Maximum tolerable dose (MTD)
Time frame: From date of enrollment until the end of 1 cycle of treatment, assessed up to 3 weeks
Determine the appropriate dose of maximum tolerable dose (MTD) of sintilimab for further clinical study in this patient population
2 secondary outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
Objective presponse rate (ORR)
Time frame: From the date of the treatment to the first evaluation (After 2 cycles of treatment assessed up to 6 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2020.
- Derived from this study: PubMed 37828033Que Y, Wang J, Sun F, Wang S, Zhu J, Huang J, Zhao Z, Zhang L, Liu J, Xu J, Zhen Z, Sun X, Lu S, Zhang Y. Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study. Signal Transduct Target Ther. 2023 Oct 13;8(1):392. doi: 10.1038/s41392-023-01636-9.
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Knowledge, Attitudes, Practice
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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sintilimab in people with Pediatric Cancer, run by Sun Yat-sen University at 1 site in China.
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 28 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 3 Sep 2020. 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 China. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yizhuo Zhang (020-87342459, zhangyzh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerable dose (MTD) (time frame: From date of enrollment until the end of 1 cycle of treatment, assessed up to 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04400851, which also lists 1 linked publication.
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 3 Sep 2020.