Refractory Malignant Solid NeoplasmPhase 1AmarettoNCT04981691
Anti-mesothelin CAR-T Cells With Advanced Refractory Solid Tumors
A Phase 1 study testing anti-MESO CAR T cells in people with Refractory Malignant Solid Neoplasm, run by Ruijin Hospital at 1 site in China.
Trial summary
The goal of this clinical trial is to study the safety, efficacy, and pharmacokinetics of mRNA-engineered anti-Mesothelin (MESO) Chimeric Antigen Receptor T-Cell (CAR-T cells) therapy in patients with mesothelin expression-positive, advanced solid tumors that have failed at least first-line or second-line therapy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Refractory Malignant Solid Neoplasm
- What is being tested?
- anti-MESO CAR T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2021to 9 Jul 2022
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and the willingness to provide written informed consent.
- Advanced pancreatic cancer, ovarian cancer, malignant mesothelioma, gastric cancer, bowel cancer, etc., diagnosed by histopathological or cytological examination, but not limited to subjects with various advanced solid tumors.
- IHC test showed Mesothelin positive expression at least 1+ in tumor tissue
- Age no less than 18 years.
- Life expectancy greater than 3 months.
- According to the RECIST (Response Evaluation Criteria in Solid Tumors) standard, there must be measurable lesions.
Show all 11Show fewer
- Evidence of metastatic disease and failure of at least 1 prior chemotherapy for metastatic disease. During the last treatment or after the treatment, the disease progressed and was confirmed (the investigator judged according to the RECIST 1.1 standard).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 during the screening period and before apheresis.
- Adequate liver/bone marrow function.
- Female subjects must meet the following conditions: infertility or fertility and use high-efficiency contraceptive measures.
- Male subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for 3 months following the last dose of the study cell infusion. Moreover, all men are absolutely prohibited from donating sperm within 1 year after receiving the last study treatment infusion.
Who cannot join
- Participated in any other trial in which receipt of an investigational study drug occurred within 28 days prior to entry into the study.
- Received any anticancer medication in the 2 weeks prior to receiving their first dose of study treatment, including but not limited to surgery, systemic chemotherapy, radiotherapy, intervention, etc.
- Uncontrolled thyroid dysfunction (serum thyroid hormone determination TT4, TT3, FT3, FT4, and serum thyroid-stimulating hormone TSH) are not suitable for enrolling in the study;
- Pregnant or breastfeeding female, or not willing to take contraception measures during the study.
- Any uncontrollable active infection, including but not limited to active tuberculosis; HBV infection (including HBsAg positive, or HBcAb positive and HBV DNA positive); HIV, syphilis, hepatitis C positive or suffering from other fatal viruses, Bacterial disease
- Administrated with steroids (5 mg/day or more dexamethasone, or equivalent hormone drugs) within the past two weeks;
Show all 18Show fewer
- Other uncontrolled diseases may cause abnormal death of the patient;
- Active autoimmune disease (including but not limited to: systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within the past 4 weeks.
- Previously allergic to immunotherapy, tocilizumab, cyclophosphamide, fludarabine, and other related drugs, previous history of severe allergies, to research product excipients (such as human serum albumin, DMSO, and dextran 40 ); people who have a history of penicillin allergy and have a positive skin test at the time of screening.
- Congestive heart failure, uncontrolled cardiac arrhythmia, etc.
- Uncontrollable massive ascites, that cannot be drained by standard methods;
- Intestinal obstruction or CT suggesting omental cake-like peritoneal metastasis, or repeated uncontrollable incomplete intestinal obstruction.
- Have received any genetic engineering modified T cell therapy (including CAR T, TCR T cell).
- Uncontrolled brain metastasis or mental illness.
- Suffered from other uncured malignant tumors within the past 3 years or at the same time.
- The blood oxygen saturation ≤95% at the time of screening and before apheresis.
- Can't be followed up or obey protocol.
- The investigator believes that it is not appropriate to participate in the trial.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Oncology, Ruijin Hospital
Shanghai, 200025
Jun Zhang, MD & Ph. D, +86-13818332497, junzhang10977@sjtu.edu.cn
Jun Zhang, MD & Ph. D
About this study
Official title: An Open, Single-center, Exploratory Clinical Trial to Evaluate the Safety and Efficacy of mRNA CAR-mesothelin T Cells in Patients With Advanced Refractory Solid Tumors
The goal of this clinical trial is to study the safety, efficacy, and pharmacokinetics of mRNA-engineered anti-Mesothelin (MESO) Chimeric Antigen Receptor T-Cell (CAR-T cells) therapy in patients with mesothelin expression-positive, advanced solid tumors that have failed at least first-line or second-line therapy.
Read the detailed description
This phase I study is being conducted to establish safety, pharmacokinetics, and preliminary efficacy of intravenous (IV) mRNA electroporated fully-humanized anti-MESO re-directed autologous T cell administration in patients with chemotherapy-refractory metastatic solid tumors.
The study will adopt the "3+3" dose escalation design exploring two doses of 1×109 and 3×109. The administration is planned to infuse 3 times a week for 2 consecutive weeks.
- The subjects will receive a total dose of 1x109 RNA transduced anti-MESO CAR-T cells in the first week, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days by intravenous infusion. If there is no obvious dose-limiting toxicity (DLT) after the first week of infusion, three times consecutive infusions of 1x109 anti-MESO CAR-T cells each time is planned in the second week. Each subject needs to be observed for at least 2 weeks (14 days) after completing the last infusion. Lymphodepleting chemotherapy will not be repeated prior to additional infusions of anti-MESO CAR-T cells.
- Conditions
- Refractory Malignant Solid Neoplasm
- Being tested
- anti-MESO CAR T cells
- Keywords
- Mesothelin, Refractory Solid Tumors, Chimeric Antigen Receptor T-Cell, Phase I clinical trial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-MESO CAR T cellsBiological
Autologous genetically modified anti-MESO CAR T cells
| Study group | Role | What they receive |
|---|---|---|
| anti-MESO CAR-T cells | Experimental | The subjects in this arm will receive Cyclophosphamide 300mg/m2/d and Fludarabine 30mg/m2/d from day-4 to day-2. Subjects will be treated with six administrations of anti-MESO CAR-T cells three times weekly (Monday-Wednesday-Friday) for two weeks. In the first week, total 1×109 or 3×109 will be infused, the second week is to plan three times consecutive infusions of 1x109 or 3×109 anti-MESO CAR-T cells each time.
Subjects will be enrolled serially. For subject safety, the preceding subject must have completed therapy and be 28 days from their last infusion before the next subject can be treated.
Interventions:
* Drug: anti-MESO CAR-T cells
* Drug: Fludarabine
* Drug: Cyclophosphamide Receives: Biological: anti-MESO CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
TEAEs
Incidence of Treatment Emergent Adverse Event
Measured: 4 weeks after the last infusion
TRAEs
Incidence of Treatment Related Adverse Events
Measured: 4 weeks after the last infusion
SIAEs and SAEs
Incidence of AEs of Special Interest and Serious Adverse Events
Measured: 4 weeks after the last infusion
DLTs
Incidence of dose-limiting toxicities
Measured: 4 weeks after the last infusion
Secondary outcomes (14)
TEAEs,TRAEs, SIAEs and SAEs
Incidence of Treatment Emergent Adverse Event, Treatment Related adverse events, AEs of special interest and serious adverse events
Measured: 12 weeks after the last infusion
ORR by IR
Objective response rate based on investigator's evaluation
Measured: 12 weeks after the last infusion
ORR by IRC
ORR based on independent review committee evaluation
Measured: 12 weeks after the last infusion
DCR by IR
Disease control rate based on the investigator's evaluation
Measured: 12 weeks after the last infusion
DCR by IRC
DCR based on IRC evaluation
Measured: 12 weeks after the last infusion
DOR by IR
Duration of Remission based on the investigator's evaluation
Measured: 12 weeks after the last infusion
TTR by IR
Time to remission based on the investigator's evaluation
Measured: 12 weeks after the last infusion
PFS by IR
Progression-free survival (PFS) based on the investigator's evaluation
Measured: 24 weeks after the last infusion
PFS by IRC
PFS based on IRC evaluation
Measured: 24 weeks after the last infusion
OS
Overall survival
Measured: 52 weeks after the last infusion
QOL
According to the EUROPEAN Organization for Research and Treatment of Cancer, Eortc, Quality of Life QuestionNare-Core 3, QOQ-C30), ERTC QLQ-C30, evaluated subject's quality of life.
Measured: 12 weeks after the last infusion
Cmax
the highest concentration (Cmax) of anti-human MESO T cells in the peripheral blood after CAR T cell infusion
Measured: 4 weeks after the last infusion
AUC
the area under the curve of 28 days of anti-human MESO T cells in the peripheral blood after CAR T cell infusion
Measured: 4 weeks after the last infusion
HACA
Positive rate of Human Anti-CAR Antibodies after CAR T cell infusion
Measured: 4 weeks after the last infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2021
- Study start1 Oct 2021 (estimated)
- Primary completion9 Jan 2022 (estimated)
- Study completion9 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by Ruijin 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Responsible party
- Principal investigator, Jun Zhang, Ruijin Hospital
- Investigators
- Jun Zhang, MD, PhD, Principal investigator, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04981691
- Sponsor's protocol ID
- Amaretto
- Acronym
- Amaretto
- Status last verified
- Sep 2021
- First submitted
- 7 Jul 2021
- Last updated
- 17 Sep 2021
- 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 17 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Single-center, Exploratory Clinical Trial to Evaluate the Safety and Efficacy of mRNA CAR-mesothelin T Cells in Patients With Advanced Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT04981691
- Acronym / sponsor ID
- Amaretto / Amaretto
- Conditions
- Refractory Malignant Solid Neoplasm
- Keywords
- Mesothelin, Refractory Solid Tumors, Chimeric Antigen Receptor T-Cell, Phase I clinical trial
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Study start
- 1 Oct 2021 (estimated)
- Primary completion
- 9 Jan 2022 (estimated)
- Study completion
- 9 Jul 2022 (estimated)
- First posted
- 29 Jul 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.
The goal of this clinical trial is to study the safety, efficacy, and pharmacokinetics of mRNA-engineered anti-Mesothelin (MESO) Chimeric Antigen Receptor T-Cell (CAR-T cells) therapy in patients with mesothelin expression-positive, advanced solid tumors that have failed at least first-line or second-line therapy.
Detailed description
This phase I study is being conducted to establish safety, pharmacokinetics, and preliminary efficacy of intravenous (IV) mRNA electroporated fully-humanized anti-MESO re-directed autologous T cell administration in patients with chemotherapy-refractory metastatic solid tumors.
The study will adopt the "3+3" dose escalation design exploring two doses of 1×109 and 3×109. The administration is planned to infuse 3 times a week for 2 consecutive weeks.
- The subjects will receive a total dose of 1x109 RNA transduced anti-MESO CAR-T cells in the first week, following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days by intravenous infusion. If there is no obvious dose-limiting toxicity (DLT) after the first week of infusion, three times consecutive infusions of 1x109 anti-MESO CAR-T cells each time is planned in the second week. Each subject needs to be observed for at least 2 weeks (14 days) after completing the last infusion. Lymphodepleting chemotherapy will not be repeated prior to additional infusions of anti-MESO CAR-T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-MESO CAR-T cells | Experimental | Biological: anti-MESO CAR T cellsThe subjects in this arm will receive Cyclophosphamide 300mg/m2/d and Fludarabine 30mg/m2/d from day-4 to day-2. Subjects will be treated with six administrations of anti-MESO CAR-T cells three times weekly (Monday-Wednesday-Friday) for two weeks. In the first week, total 1×109 or 3×109 will be infused, the second week is to plan three times consecutive infusions of 1x109 or 3×109 anti-MESO CAR-T cells each time. Subjects will be enrolled serially. For subject safety, the preceding subject must have completed therapy and be 28 days from their last infusion before the next subject can be treated. Interventions: * Drug: anti-MESO CAR-T cells * Drug: Fludarabine * Drug: Cyclophosphamide |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Ability to understand and the willingness to provide written informed consent.
- Advanced pancreatic cancer, ovarian cancer, malignant mesothelioma, gastric cancer, bowel cancer, etc., diagnosed by histopathological or cytological examination, but not limited to subjects with various advanced solid tumors.
- IHC test showed Mesothelin positive expression at least 1+ in tumor tissue
- Age no less than 18 years.
- Life expectancy greater than 3 months.
Key exclusion criteria (18 listed)
- Participated in any other trial in which receipt of an investigational study drug occurred within 28 days prior to entry into the study.
- Received any anticancer medication in the 2 weeks prior to receiving their first dose of study treatment, including but not limited to surgery, systemic chemotherapy, radiotherapy, intervention, etc.
- Uncontrolled thyroid dysfunction (serum thyroid hormone determination TT4, TT3, FT3, FT4, and serum thyroid-stimulating hormone TSH) are not suitable for enrolling in the study;
- Pregnant or breastfeeding female, or not willing to take contraception measures during the study.
- Any uncontrollable active infection, including but not limited to active tuberculosis; HBV infection (including HBsAg positive, or HBcAb positive and HBV DNA positive); HIV, syphilis, hepatitis C positive or suffering from other fatal viruses, Bacterial disease
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 |
|---|---|---|
| anti-MESO CAR T cellsAutologous genetically modified anti-MESO CAR T cells | Biological | anti-MESO CAR-T cells |
Primary outcome
TEAEs
Time frame: 4 weeks after the last infusion
Incidence of Treatment Emergent Adverse Event
TRAEs
Time frame: 4 weeks after the last infusion
Incidence of Treatment Related Adverse Events
SIAEs and SAEs
Time frame: 4 weeks after the last infusion
Incidence of AEs of Special Interest and Serious Adverse Events
DLTs
Time frame: 4 weeks after the last infusion
Incidence of dose-limiting toxicities
14 secondary outcomes
TEAEs,TRAEs, SIAEs and SAEs
Time frame: 12 weeks after the last infusion
ORR by IR
Time frame: 12 weeks after the last infusion
ORR by IRC
Time frame: 12 weeks after the last infusion
DCR by IR
Time frame: 12 weeks after the last infusion
DCR by IRC
Time frame: 12 weeks after the last infusion
DOR by IR
Time frame: 12 weeks after the last infusion
TTR by IR
Time frame: 12 weeks after the last infusion
PFS by IR
Time frame: 24 weeks after the last infusion
PFS by IRC
Time frame: 24 weeks after the last infusion
OS
Time frame: 52 weeks after the last infusion
QOL
Time frame: 12 weeks after the last infusion
Cmax
Time frame: 4 weeks after the last infusion
AUC
Time frame: 4 weeks after the last infusion
HACA
Time frame: 4 weeks after the last infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2021.
- Individual participant dataSharing planned: No
Related trials for Refractory Malignant Solid Neoplasm
RecruitingPhase 1/2
A Study of Ifinatamab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01D/LIGHTBEAM-U01)
Malignant Neoplasm
RecruitingObservational study
Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
Malignant Solid Tumors, Other Neoplasms Solid Tumors
Active, not recruitingPhase 2
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm
Active, not recruitingPhase 2
Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Jun Zhang, MD, PhD principal investigator
Ruijin 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 anti-MESO CAR T cells in people with Refractory Malignant Solid Neoplasm, run by Ruijin 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 11 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: status not confirmed, as of the sponsor's last update on 17 Sep 2021. 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 Jun Zhang, MD, PhD (0086-13818332497, junzhang10977@sjtu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TEAEs (time frame: 4 weeks after the last infusion). The study lists 4 primary outcomes in all. 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 17 Sep 2021.