Solid TumorPhase 1NCT04944888
GSL Synthetase Inhibitor in Combination With Immune Checkpoint Inhibitor in Previously Treated Blood and Solid Tumor
A Phase 1 study testing Eliglustat and Immune checkpoint inhibitor in people with Solid Tumor and Hematologic Malignancy, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Immune checkpoint blockade has made great but unsatisfied success in treating cancers. One important reason is the hijacked HLA (Human Leukocyte Antigen) antigen presentation. Eliglustat could inhibit glycosphingolipids synthesis and restore HLA-I antigen presentation and transform the immunogenicity of tumor cells. Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Solid Tumor, Hematologic Malignancy
- What is being tested?
- Eliglustat and Immune checkpoint inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2021to 30 Nov 2023
- 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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age from 16 to 75 years with estimated life expectancy >3 months.
- Histopathological confirmed advanced or metastatic systematically pretreated solid tumors and relapsed/refractory hematological malignancies.
- Have at least one measurable target lesion for solid tumors.
- Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 3 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
- Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
- Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.
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- Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
- Previous treatment with anti-PD-1/PD-L1 antibodies or cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors are allowed.
- Ability to understand and sign a written informed consent document.
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.
Who cannot join
- Patients are unwilling to comply with the requirements of the protocol.
- The patient has documented prior esophageal varices or liver infarction or current liver enzymes (alanine transaminase, aspartate aminotransferase) or total bilirubin >3 times the upper limit of normal.
- The patient is known to have any of the following: cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, current treatment with Class IA or Class III antiarrhythmic medicinal products, interstitial lung disease of any grade or severely impaired pulmonary function.
- Uncontrolled intercurrent illness, including ongoing or active systemic infection or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
- The patients is taking a CYP2D6 inhibitor and/or concomitantly with a strong or moderate CYP3A inhibitor.
- Active, known or suspected autoimmune diseases.
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- Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
- Patients are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- History of severe hypersensitive reactions to other monoclonal antibodies.
- History of allergy or intolerance to study drug components.
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
- History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
- Vaccination within 30 days of study enrollment.
- Active bleeding or known hemorrhagic tendency.
- Subjects with unhealed surgical wounds for more than 30 days.
- Being participating any other trials or withdraw within 4 weeks.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase ⅠStudy of GSL Synthetase Inhibitor in Combination With Immune Checkpoint Inhibitor in Treating Patients With Advanced Relapsed or Refractory Hematological Malignancies and Previously Treated Solid Tumors
Immune checkpoint blockade has made great but unsatisfied success in treating cancers. One important reason is the hijacked HLA (Human Leukocyte Antigen) antigen presentation. Eliglustat could inhibit glycosphingolipids synthesis and restore HLA-I antigen presentation and transform the immunogenicity of tumor cells. Therefore,GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer.
Read the detailed description
Immune checkpoint blockade has led to great strides in the management of various cancers, however, durable response could be seen in approximately 20% of treated patients with most solid tumors and hematological malignancies. One important reason is that tumor cells often escape from immune surveillance by downregulating one or multiple molecules critical in HLA antigen presentation. As a consequence, options that could restore HLA antigen presentation may augment immune checkpoint inhibitor-mediated immune responses.
Abnormal expression of glycosphingolipid (GSL) synthetase is a basic and specific characteristic of most tumors and tumor microenvironment, such as Globo H Ceramide, which is overexpressed in multiple epithelial-derived tumors. Several studies also reported that GSL synthetase was overexpressed in chemotherapy-resistant tumors. Eliglustat is an orally GlcCer synthase inhibitor, which is approved for treating Type-1 Gaucher disease. However, one most recent study reveals that it could inhibit glycosphingolipids synthesis and restore HLA antigen presentation, and transforming the immunogenicity of tumor cells. Therefore, GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer.
The primary objective of this study is to assess the safety and feasibility of GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor in patients with relapsed or refractory hematological malignancies and solid tumors. The secondary objectives include assessing antitumor activity, pharmacokinetics and pharmacodynamics. The exploratory objectives are to evaluate the pathological, immunological or clinical predictive biomarkers for efficacy and toxicity, transformation of tumor microenvironment and dynamic changes of immune cells in peripheral blood.
- Conditions
- Solid Tumor, Hematologic Malignancy
- Being tested
- Eliglustat, Immune checkpoint inhibitor
- Keywords
- GSL synthetase inhibitor, Immune checkpoint inhibitor, Solid tumor, Hematologic Malignancy
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EliglustatDrug
Eliglustat will be given to enrolled patients at dose of 84mg daily (dose 1) , and then at dose of 84mg twice daily (dose 2).
Immune checkpoint inhibitorDrug
immune checkpoint inhibitor (physician decided).
| Study group | Role | What they receive |
|---|---|---|
| Experimental Dose 1 | Experimental | Eliglustat 84mg will be administered once daily in patients who are CYP2D6 ultra-rapid metabolizers (URMs), extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs), in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 84mg will be daily administered every other week to 96 weeks.
Immune checkpoint inhibitor (physician decided) will be administered intravenously on day 5 or day 15 every 3 weeks. For patients who still benefit from the trial, immune checkpoint inhibitor will be administered every 3 week to 96 weeks. Receives: Drug: Eliglustat; Drug: Immune checkpoint inhibitor |
| Experimental Dose 2 | Experimental | Eliglustat 84mg will be administered twice daily in patients who are CYP2D6 ultra-rapid metabolizers (URMs), extensive metabolizers (EMs), or intermediate metabolizers (IMs), or in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 84mg will be administered twice daily every other week to 96 weeks.
Immune checkpoint inhibitor (physician decided) will be administered intravenously on day 5 or day 15 every 3 weeks. For patients who still benefit from the trial, immune checkpoint inhibitor will be administered every 3 week to 96 weeks. Receives: Drug: Eliglustat; Drug: Immune checkpoint inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects occuring treatment related adverse events
Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0
Measured: Up to 90 days after the last dose of study drugs.
Secondary outcomes (1)
The percentage of enrolled patients that respond to the treatment
Overall response rate is defined as the sum of partial responses and complete responses
Measured: Up to 120 days after the last dose of study drugs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study start1 Jul 2021
- Primary completion30 Nov 2023
- Study completion30 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Weidong Han, PhD, Principal investigator, Biotherapeutic Department, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04944888
- Sponsor's protocol ID
- CHN-PLAGH-BT-065
- Status last verified
- Dec 2023
- First submitted
- 23 Jun 2021
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- 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 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase ⅠStudy of GSL Synthetase Inhibitor in Combination With Immune Checkpoint Inhibitor in Treating Patients With Advanced Relapsed or Refractory Hematological Malignancies and Previously Treated Solid Tumors
- ClinicalTrials.gov ID
- NCT04944888
- Acronym / sponsor ID
- CHN-PLAGH-BT-065
- Conditions
- Solid Tumor, Hematologic Malignancy
- Keywords
- GSL synthetase inhibitor, Immune checkpoint inhibitor, Solid tumor, Hematologic Malignancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 30 Jun 2021 (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.
Immune checkpoint blockade has made great but unsatisfied success in treating cancers. One important reason is the hijacked HLA (Human Leukocyte Antigen) antigen presentation. Eliglustat could inhibit glycosphingolipids synthesis and restore HLA-I antigen presentation and transform the immunogenicity of tumor cells. Therefore,GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer.
Detailed description
Immune checkpoint blockade has led to great strides in the management of various cancers, however, durable response could be seen in approximately 20% of treated patients with most solid tumors and hematological malignancies. One important reason is that tumor cells often escape from immune surveillance by downregulating one or multiple molecules critical in HLA antigen presentation. As a consequence, options that could restore HLA antigen presentation may augment immune checkpoint inhibitor-mediated immune responses.
Abnormal expression of glycosphingolipid (GSL) synthetase is a basic and specific characteristic of most tumors and tumor microenvironment, such as Globo H Ceramide, which is overexpressed in multiple epithelial-derived tumors. Several studies also reported that GSL synthetase was overexpressed in chemotherapy-resistant tumors. Eliglustat is an orally GlcCer synthase inhibitor, which is approved for treating Type-1 Gaucher disease. However, one most recent study reveals that it could inhibit glycosphingolipids synthesis and restore HLA antigen presentation, and transforming the immunogenicity of tumor cells. Therefore, GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer.
The primary objective of this study is to assess the safety and feasibility of GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor in patients with relapsed or refractory hematological malignancies and solid tumors. The secondary objectives include assessing antitumor activity, pharmacokinetics and pharmacodynamics. The exploratory objectives are to evaluate the pathological, immunological or clinical predictive biomarkers for efficacy and toxicity, transformation of tumor microenvironment and dynamic changes of immune cells in peripheral blood.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Dose 1 | Experimental | Drug: Eliglustat, Drug: Immune checkpoint inhibitorEliglustat 84mg will be administered once daily in patients who are CYP2D6 ultra-rapid metabolizers (URMs), extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs), in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 84mg will be daily administered every other week to 96 weeks. Immune checkpoint inhibitor (physician decided) will be administered intravenously on day 5 or day 15 every 3 weeks. For patients who still benefit from the trial, immune checkpoint inhibitor will be administered every 3 week to 96 weeks. |
| Experimental Dose 2 | Experimental | Drug: Eliglustat, Drug: Immune checkpoint inhibitorEliglustat 84mg will be administered twice daily in patients who are CYP2D6 ultra-rapid metabolizers (URMs), extensive metabolizers (EMs), or intermediate metabolizers (IMs), or in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 84mg will be administered twice daily every other week to 96 weeks. Immune checkpoint inhibitor (physician decided) will be administered intravenously on day 5 or day 15 every 3 weeks. For patients who still benefit from the trial, immune checkpoint inhibitor will be administered every 3 week to 96 weeks. |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age from 16 to 75 years with estimated life expectancy >3 months.
- Histopathological confirmed advanced or metastatic systematically pretreated solid tumors and relapsed/refractory hematological malignancies.
- Have at least one measurable target lesion for solid tumors.
- Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 3 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
- Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
Key exclusion criteria (18 listed)
- Patients are unwilling to comply with the requirements of the protocol.
- The patient has documented prior esophageal varices or liver infarction or current liver enzymes (alanine transaminase, aspartate aminotransferase) or total bilirubin >3 times the upper limit of normal.
- The patient is known to have any of the following: cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, current treatment with Class IA or Class III antiarrhythmic medicinal products, interstitial lung disease of any grade or severely impaired pulmonary function.
- Uncontrolled intercurrent illness, including ongoing or active systemic infection or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
- The patients is taking a CYP2D6 inhibitor and/or concomitantly with a strong or moderate CYP3A inhibitor.
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 |
|---|---|---|
| EliglustatEliglustat will be given to enrolled patients at dose of 84mg daily (dose 1) , and then at dose of 84mg twice daily (dose 2). | Drug | Experimental Dose 1, Experimental Dose 2 |
| Immune checkpoint inhibitorimmune checkpoint inhibitor (physician decided). | Drug | Experimental Dose 1, Experimental Dose 2 |
Primary outcome
Number of subjects occuring treatment related adverse events
Time frame: Up to 90 days after the last dose of study drugs.
Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0
1 secondary outcome
The percentage of enrolled patients that respond to the treatment
Time frame: Up to 120 days after the last dose of study drugs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 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. This study is not recruiting at the moment.
Weidong Han, PhD principal investigator
Biotherapeutic Department, Chinese PLA General Hospital
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 Eliglustat and Immune checkpoint inhibitor in people with Solid Tumor and Hematologic Malignancy, run by Chinese PLA General Hospital 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 10 inclusion and 18 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: finished, as of the sponsor's last update on 19 Dec 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects occuring treatment related adverse events (time frame: Up to 90 days after the last dose of study drugs.). 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 19 Dec 2023.