Trial Title:
IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma
NCT ID:
NCT06412458
Condition:
Refractory Osteosarcoma
Recurrent Osteosarcoma
Conditions: Official terms:
Osteosarcoma
Conditions: Keywords:
IM83 CAR-T
Relapsed or refractory osteosarcoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
IM83 CAR-T Cells
Description:
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.
Arm group label:
IM83 CAR-T Cells
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
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 16 years, both male and female;
2. Subjects with a diagnosis of osteosarcoma of the extremity confirmed by
pathohistologic examination;
3. 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:
1. 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.);
2. 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;
3. 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.
Exclusion Criteria:
1. Presence of brain metastases;
2. Subjects who have previously received or are awaiting an organ transplant;
3. Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in
cases judged by the investigator to be not clinically significant);
4. 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;
5. Use of any of the following medications or treatments during the designated time
period prior to cell collection:
1. Surgical treatment, interventional therapy, radiotherapy, ablation, and other
localized treatments for the study disease within 4 weeks prior to cell
collection;
2. 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;
3. Immunotherapy with anti-PD1, PD-L1, etc. within 4 weeks prior to cell
collection;
4. Therapeutic doses of corticosteroids have been used within 3 days prior to cell
collection. However, topical and inhaled steroids are permitted;
6. 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;
7. Previously treated with targeted GPC3 therapy (can be enrolled if still positive for
GPC3 expression upon testing);
8. Those who have previously received other cellular therapy or genetically modified
cellular therapy, such as TCR-T therapy, CAR-T therapy, etc;
9. 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;
10. Presence of chronic obstructive pulmonary disease (COPD), interstitial lung disease
(ILD), and clinically significant pulmonary function test abnormalities;
11. 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;
12. 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;
13. 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;
14. 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;
15. 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;
16. Subjects requiring anticoagulation therapy;
17. Subjects requiring long-term antiplatelet therapy;
18. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months
prior to initiation of screening;
19. 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;
20. 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.
Gender:
All
Minimum age:
16 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Guangdong Provincial People's Hospital
Address:
City:
Guangdong
Zip:
519041
Country:
China
Start date:
June 15, 2024
Completion date:
June 15, 2026
Lead sponsor:
Agency:
Beijing Immunochina Medical Science & Technology Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
Guangdong Provincial People's Hospital
Agency class:
Other
Source:
Beijing Immunochina Medical Science & Technology Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06412458
