Refractory OsteosarcomaPhase 1NCT06412458
IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma
A Phase 1 study testing IM83 CAR-T Cells in people with Refractory Osteosarcoma and Recurrent Osteosarcoma, run by Beijing Immunochina Medical Science & Technology Co., Ltd. at 1 site in China.
Trial summary
The purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Refractory Osteosarcoma, Recurrent Osteosarcoma
- What is being tested?
- IM83 CAR-T Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteChina
- Study dates
- 15 Jun 2024to 15 Jun 2026
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 16 years, both male and female;
- Subjects with a diagnosis of osteosarcoma of the extremity confirmed by pathohistologic examination;
- To enroll subjects with recurrent or refractory extremity osteosarcoma who have failed or are intolerant to first-line standard therapy and who are not candidates for radical surgery and/or localized therapy and who lack effective subsequent treatment.
- Notes:
- Standard treatment failure was defined as disease relapse or progression during or within 6 months of completion of treatment with first-line chemotherapeutic agents (including high-dose methotrexate, doxorubicin, cisplatin, isocyclophosphamide, etc.);
- Requirement of treatment intolerance: means that the subject is unable to continue the current effective systemic regimen due to the development of toxic side effects such as ≥ grade 3 vomiting, diarrhea, abdominal pain, myelosuppression, etc., and that refusal is not accepted for financial and personal reasons;
- The standard treatment received by the subject must be in accordance with the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Bone and Soft Tissue Tumors, 2023 Edition; 4. At least one measurable target lesion according to RECIST 1.1 criteria; 5. Subjects must provide a tumor tissue sample (paraffin block or number of unstained sections meeting the testing requirements specified by the Institute) within 2 years that meets the requirements to be tested by immunohistochemistry for GPC3 and CD40 and needs to be positive for GPC3 expression;; 6. Karnofsky functional status score ≥60; 7. Expected survival ≥ 12 weeks; 8. Laboratory tests should meet at least the indicators specified below:
- 1)Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; 2)Absolute lymphocyte cell count (LY) ≥ 0.6 x 10^9/L; 3)Lymphocytes make up ≥10% of white blood cells; 4)Platelets ≥75 x 10^9/L; 5)Hemoglobin ≥ 90 g/L; 6)Creatinine clearance ≥60 ml/min; 7)Serum bilirubin ≤ 1.5 times the upper limit of normal; if liver metastases are present, serum bilirubin ≤ 3.0 times the upper limit of normal; 8)Prolongation of prothrombinogen time ≤ 4s; 9)≤ 2.5 times the upper limit of normal for albumin transaminase (AST) and albumin transaminase (ALT); if liver metastases are present, ALT and/or AST ≤ 5.0 times the upper limit of normal; 9. Left ventricular ejection fraction was >50%; 10. Oxygen saturation >92% in the non-oxygenated state; 11. Women of childbearing potential who had a negative blood pregnancy test prior to the start of the trial and who agreed to use effective contraception for the duration of the trial up to the last follow-up visit; male subjects whose partners were of childbearing potential agreed to use effective contraception for the duration of the trial up to the last follow-up visit; 12. Vascular access is adequate for cell collection, and lines are available for subjects with existing central venous catheters; 13. I or my legal guardian/proxy agree to participate in this trial and sign the informed consent form.
Who cannot join
- Presence of brain metastases;
- Subjects who have previously received or are awaiting an organ transplant;
- Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in cases judged by the investigator to be not clinically significant);
- Autoimmune diseases requiring systemic immunosuppressive therapy, such as systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis, within 2 years prior to the start of screening;
- Use of any of the following medications or treatments during the designated time period prior to cell collection:
- Surgical treatment, interventional therapy, radiotherapy, ablation, and other localized treatments for the study disease within 4 weeks prior to cell collection;
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- Subjects who have had major surgery or significant trauma within 4 weeks prior to cell collection, or who are expected to require major surgery during the study period;
- Immunotherapy with anti-PD1, PD-L1, etc. within 4 weeks prior to cell collection;
- Therapeutic doses of corticosteroids have been used within 3 days prior to cell collection. However, topical and inhaled steroids are permitted;
- Other untreated malignant tumors within the previous 5 years or concurrently, except cervical cancer in situ, basal cell carcinoma of the skin, and ductal carcinoma in situ of the breast;
- Previously treated with targeted GPC3 therapy (can be enrolled if still positive for GPC3 expression upon testing);
- Those who have previously received other cellular therapy or genetically modified cellular therapy, such as TCR-T therapy, CAR-T therapy, etc;
- Prior or clinically significant CNS disorders at screening, such as epilepsy, seizures, cerebrovascular disease (ischemia/hemorrhage/infarction), cerebral edema, reversible posterior leukoencephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, or psychiatric disorders;
- Presence of chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and clinically significant pulmonary function test abnormalities;
- Subjects assessed by the investigator as having a significant amount of plasmapheresis (e.g., pleural effusion, peritoneal effusion, pericardial effusion) that cannot be controlled with treatment;
- Medication-uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >90 mmHg) or the presence of clinically significant (e.g., active) cardiovascular disease, such as cerebrovascular accident, myocardial infarction, unstable angina pectoris, or severe cardiac arrhythmia that is uncontrolled with medication or that has a potential impact on the study treatment in the 6 months prior to the date of signing of the informed consent;
- Subjects who are positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and have a peripheral blood HBV-DNA test higher than the lower limit of detection (HBsAg-positive but with a peripheral blood HBV-DNA test lower than the lower limit of detection according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B, Version 2022, at least at least 4 weeks of antiviral therapy is required prior to the first administration of the investigational drug, and during the course of the study Ongoing antiviral therapy for 6-12 months with monitoring of HBV DNA, HBsAg, and ALT levels every 1-3 months); Hepatitis C virus (HCV) antibody positive and peripheral blood HCV-RNA test above the lower limit of detection; HIV antibody positive; syphilis antibody positive;
- Active EBV and cytomegalovirus, defined as subjects with IgM antibody-positive or IgM antibody-negative EBV serum but higher-than-normal EBV-DNA; and cytomegalovirus (CMV) serum IgM antibody-positive or IgM antibody-negative cytomegalovirus but higher-than-normal CMV-DNA;
- Abnormalities of cardiac function include: long QTc syndrome or QTc interval >480 ms; complete left bundle branch block, degree II/III AV block; severe, uncontrolled arrhythmia requiring pharmacologic therapy; history of chronic congestive heart failure with NYHA class ≥3 (refer to Appendix 3) cardiac ejection fraction less than 50% in the 6 months prior to screening; CTCAE ≥3 grade heart valve disease; myocardial infarction, cardiac angioplasty or stenting, unstable angina, history of severe pericardial disease, or other clinically significant cardiac disease within 6 months prior to screening;
- Subjects requiring anticoagulation therapy;
- Subjects requiring long-term antiplatelet therapy;
- History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to initiation of screening;
- Infections (fungal, bacterial, viral, or other) that require intravenous antimicrobial control or are uncontrollable, for simple urinary tract infections, and for bacterial pharyngitis, may be enrolled if the investigator evaluates that they can be controlled by curative treatment;
- The presence of any factors affecting compliance with the protocol, or the unwillingness or inability of the subject to comply with the procedures required in the study protocol, as judged by the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Clinical Study to Evaluate the Safety and Efficacy of IM83 CAR-T Cells for the Treatment of Relapsed or Refractory Osteosarcoma
The purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma
Read the detailed description
This study is planned to enroll 9-18 patients with relapsed or refractory osteosarcoma in a modified "3+3" design for dose escalation, with three dose groups of 5×10^8 cells, 1×10^9 cells, and 2×10^9 cells.3-6 subjects are planned to be enrolled in each dose group to assess their safety. Each dose group is planned to enroll 3-6 subjects to assess safety, and if the incidence of horizontal dose-limiting toxicity (DLT) is ≤1/6 within 28 days after transfusion in a dose group, the transfusion of cells from the next dose group can be initiated.
This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.
- Conditions
- Refractory Osteosarcoma, Recurrent Osteosarcoma
- Being tested
- IM83 CAR-T Cells
- Keywords
- IM83 CAR-T, Relapsed or refractory osteosarcoma
- Medical subject headings
- Osteosarcoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IM83 CAR-T CellsBiological
IM83 CAR-T Cells, 5×10^8 cells, 1×10^9 cells, and 2×10^9 cells, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 30 mg/m^2 (D-5~D- 3), determined by tumor burden at baseline. Drug: Fludarabine Recommendation: 30 mg/m^2 (D-5~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 300 mg/ m^2 (D-5~D-3), determined by tumor burden at baseline.
| Study group | Role | What they receive |
|---|---|---|
| IM83 CAR-T Cells | Experimental | After preconditioning with chemotherapy, IM83 CAR-T Cells will be evaluated Receives: Biological: IM83 CAR-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment Related adverse events (AEs)
Incidence of Adverse Events and Abnormal Findings on Clinically Significant Laboratory Tests Associated with IM83 CAR-T Cell Therapy Within 28 Days of Infusion
Measured: Up to 28 days after CAR-T cell infusion
Secondary outcomes (8)
Objective response rate (ORR)
Objective remission rate (ORR) after infusion
Measured: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
Disease control rate (DCR)
Post-infusion disease control rate (DCR)
Measured: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
Duration of response (DOR)
Duration of disease remission (DoR) after infusion
Measured: At 28 days, 3 months and 6 months after CAR-T cell infusion
Progress free survival (PFS)
Progress free survival (PFS) after infusion
Measured: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
Overall Survival (OS)
Overall Survival (OS)
Measured: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
AUC (Area Under Curve) 0-D28
AUC 0-D28 of IM83 CAR-T cells in vivo (peripheral blood) after infusion
Measured: Up to 28 days after CAR-T cell infusion
AUC (Area Under Curve) 0-D90
AUC 0-D90 of IM83 CAR-T cells in vivo (peripheral blood) after infusion
Measured: Up to 90 days after CAR-T cell infusion
Cmax (Peak Concentration)
Peak Concentrationof IM83 CAR-T cells in vivo (peripheral blood) after infusion
Measured: Up to 28 days after CAR-T cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2024
- Study start15 Jun 2024 (estimated)
- Primary completion15 Jun 2025 (estimated)
- Study completion15 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory OsteosarcomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Immunochina Medical Science & Technology Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Guangdong Provincial People's Hospital
- Responsible party
- Sponsor
- Investigators
- Yu Zhang, PhD, Principal investigator, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06412458
- Sponsor's protocol ID
- IM83-002
- Status last verified
- May 2024
- First submitted
- 23 Apr 2024
- Last updated
- 14 May 2024
- 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 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Study to Evaluate the Safety and Efficacy of IM83 CAR-T Cells for the Treatment of Relapsed or Refractory Osteosarcoma
- ClinicalTrials.gov ID
- NCT06412458
- Acronym / sponsor ID
- IM83-002
- Conditions
- Refractory Osteosarcoma, Recurrent Osteosarcoma
- Keywords
- IM83 CAR-T, Relapsed or refractory osteosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Beijing Immunochina Medical Science & Technology Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Guangdong Provincial People's Hospital
- Study start
- 15 Jun 2024 (estimated)
- Primary completion
- 15 Jun 2025 (estimated)
- Study completion
- 15 Jun 2026 (estimated)
- First posted
- 14 May 2024 (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 purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma
Detailed description
This study is planned to enroll 9-18 patients with relapsed or refractory osteosarcoma in a modified "3+3" design for dose escalation, with three dose groups of 5×10^8 cells, 1×10^9 cells, and 2×10^9 cells.3-6 subjects are planned to be enrolled in each dose group to assess their safety. Each dose group is planned to enroll 3-6 subjects to assess safety, and if the incidence of horizontal dose-limiting toxicity (DLT) is ≤1/6 within 28 days after transfusion in a dose group, the transfusion of cells from the next dose group can be initiated.
This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IM83 CAR-T Cells | Experimental | Biological: IM83 CAR-T CellsAfter preconditioning with chemotherapy, IM83 CAR-T Cells will be evaluated |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 16 years, both male and female;
- Subjects with a diagnosis of osteosarcoma of the extremity confirmed by pathohistologic examination;
- To enroll subjects with recurrent or refractory extremity osteosarcoma who have failed or are intolerant to first-line standard therapy and who are not candidates for radical surgery and/or localized therapy and who lack effective subsequent treatment.
- Standard treatment failure was defined as disease relapse or progression during or within 6 months of completion of treatment with first-line chemotherapeutic agents (including high-dose methotrexate, doxorubicin, cisplatin, isocyclophosphamide, etc.);
- Requirement of treatment intolerance: means that the subject is unable to continue the current effective systemic regimen due to the development of toxic side effects such as ≥ grade 3 vomiting, diarrhea, abdominal pain, myelosuppression, etc., and that refusal is not accepted for financial and personal reasons;
Key exclusion criteria (24 listed)
- Presence of brain metastases;
- Subjects who have previously received or are awaiting an organ transplant;
- Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in cases judged by the investigator to be not clinically significant);
- Autoimmune diseases requiring systemic immunosuppressive therapy, such as systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis, within 2 years prior to the start of screening;
- Use of any of the following medications or treatments during the designated time period prior to cell collection:
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 |
|---|---|---|
| IM83 CAR-T CellsIM83 CAR-T Cells, 5×10^8 cells, 1×10^9 cells, and 2×10^9 cells, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 30 mg/m^2 (D-5~D- 3), determined by tumor burden at baseline. Drug: Fludarabine Recommendation: 30 mg/m^2 (D-5~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 300 mg/ m^2 (D-5~D-3), determined by tumor burden at baseline. | Biological | IM83 CAR-T Cells |
Primary outcome
Incidence of Treatment Related adverse events (AEs)
Time frame: Up to 28 days after CAR-T cell infusion
Incidence of Adverse Events and Abnormal Findings on Clinically Significant Laboratory Tests Associated with IM83 CAR-T Cell Therapy Within 28 Days of Infusion
8 secondary outcomes
Objective response rate (ORR)
Time frame: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
Disease control rate (DCR)
Time frame: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
Duration of response (DOR)
Time frame: At 28 days, 3 months and 6 months after CAR-T cell infusion
Progress free survival (PFS)
Time frame: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
Overall Survival (OS)
Time frame: At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion
AUC (Area Under Curve) 0-D28
Time frame: Up to 28 days after CAR-T cell infusion
AUC (Area Under Curve) 0-D90
Time frame: Up to 90 days after CAR-T cell infusion
Cmax (Peak Concentration)
Time frame: Up to 28 days after CAR-T cell infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- 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.
Yu Zhang, PhD principal investigator
Guangdong Provincial People's 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 IM83 CAR-T Cells in people with Refractory Osteosarcoma and Recurrent Osteosarcoma, run by Beijing Immunochina Medical Science & Technology Co., Ltd. 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 8 inclusion and 24 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 14 May 2024. 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 Yu Zhang, PhD (8620 83827812, luck_2001@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment Related adverse events (AEs) (time frame: Up to 28 days after CAR-T cell infusion). 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 14 May 2024.