NCT07676006尚未招募1 期
A Clinical Study to Investigate the Safety and Efficacy of Off-the-Shelf iNKT Cell Injection Targeting CD33/CD70 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia
Grit Biotechnology1 个研究点 分布在 1 个国家目标入组 36 人开始时间: 2027年5月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Proportion of participants experiencing dose limiting toxicity
研究概览
简要总结
This is a single-arm, open-label, dose-escalation, prospective exploratory clinical study intended to evaluate the safety, efficacy and cellular pharmacokinetics of GT737 cells in adult patients with relapsed/refractory acute myeloid leukemia (AML).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Voluntarily participate in this clinical study, fully understand the study content, sign the informed consent form, and be willing to comply with all study procedures and complete all follow-up visits.
- •2. Aged between 18 and 75 years old (inclusive), with no restriction on gender.
- •3. Confirmed diagnosis of relapsed/refractory acute myeloid leukemia (AML) per the 2016 WHO Classification, with the specific definitions as follows:
- •Confirmed AML with bone marrow blasts ≥5% at screening, and meeting any one of the following criteria:
- •Relapsed disease: Relapse after achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following standard induction chemotherapy;
- •Refractory disease: a) Failure to achieve CR/CRi after 2 cycles of induction chemotherapy; b) Relapse within 12 months of first remission with no response to subsequent re-treatment; c) Relapse after autologous or allogeneic hematopoietic stem cell transplantation; d) Failure to achieve CR/CRi after at least two lines of salvage therapy.
- •4. Confirmed positive expression of CD33 or CD70 via flow cytometry and/or immunohistochemistry.
- •5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •6. Estimated survival of more than 12 weeks.
- •7. Toxicities resulting from prior therapies must be stabilized and recovered to Grade ≤1 (alopecia and other toxicities with no significant clinical impact are excluded).
- •8. Adequate hepatic, renal, pulmonary and cardiac function, meeting the following specific criteria:
- •o Estimated creatinine clearance (calculated via the Cockcroft-Gault formula) ≥60 mL/min;
- •o Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤2.5 times the upper limit of normal (ULN);
- •o Total bilirubin ≤1.5 mg/dL (participants with Gilbert's syndrome excluded from this criterion);
- •o Cardiac ejection fraction ≥50%, no evidence of pleural effusion on echocardiogram (ECHO), and no clinically significant abnormalities on electrocardiogram (ECG);
- •o Absence of clinically significant pleural effusion;
- •o Baseline oxygen saturation >92% while breathing room air.
- •9. Females of childbearing potential: Serum or urine pregnancy test negative at screening (subjects with surgical sterilization or menopause for ≥2 years are not considered of childbearing potential). Must agree to use highly effective and reliable contraception for 1 year after receiving study treatment, and refrain from oocyte donation.
- •10. Male participants: If sexually active with females of childbearing potential, must agree to use highly effective and reliable contraception for 1 year after receiving study treatment, and refrain from sperm donation.
排除标准
- •1. Prior history of central nervous system (CNS) leukemia; or intracranial magnetic resonance imaging (MRI)/PET-CT at screening suggestive of CNS leukemia; or malignant cells identified in cerebrospinal fluid (CSF).
- •2. Other untreated malignant neoplasms diagnosed within the past 5 years or concurrent malignancies (Exceptions: adequately treated cervical carcinoma in situ, localized cutaneous squamous cell carcinoma, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, urothelial carcinoma ≤T1; participants with prostate cancer under active surveillance are eligible).
- •3. Prior receipt of CD33- or CD70-targeted cellular therapies including CAR-T, NK or iNKT cells (Excluding subjects previously treated with GT737 who qualify for re-treatment).
- •4. Systemic corticosteroids administered within 7 days prior to cell infusion (Exceptions: inhaled corticosteroids and subjects with prior allogeneic transplantation history).
- •5. History of hypersensitivity to any component of investigational products to be used in this study, including but not limited to GT737 cell infusion product, cyclophosphamide and fludarabine.
- •6. Uncontrolled suspected or confirmed fungal, bacterial, viral or other infections, or infections requiring intravenous (IV) antimicrobial therapy (Excluding prophylactic antimicrobial treatment).
- •7. Positive test results for any of the following: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, cytomegalovirus IgM (CMV-IgM), Epstein-Barr virus IgM (EBV-IgM).
- •8. Active hepatitis B (positive HBV-DNA) and/or active hepatitis C (positive HCV RNA).
- •Participants positive for HBsAg/HBcAb must undergo HBV-DNA testing; those with negative HBV-DNA may be enrolled. Post-enrollment, prophylactic antiviral therapy shall be administered if clinically indicated per investigator assessment.
- •Subjects with negative HCV antibody are eligible for enrollment. Participants with positive HCV antibody must receive HCV RNA testing and may be enrolled only if HCV RNA is negative.
- •9. Presence of any indwelling line or drainage tube (Exceptions: dedicated central venous access catheters such as Port-a-Cath and Hickman catheter).
- •10. Current or prior central nervous system disorders including seizures, cerebral ischemic/hemorrhagic events, dementia, cerebellar disease, or any autoimmune disease involving the CNS.
- •11. Cardiac involvement secondary to acute myeloid leukemia.
- •12. Occurrence of any of the following within 6 months prior to signing the informed consent form:
- •Uncontrolled congestive heart failure (New York Heart Association Class III-IV), angina pectoris, myocardial infarction, cardiomyopathy;
- •Stroke (Excluding lacunar infarction), coronary or peripheral artery bypass graft surgery;
- •Clinically significant arrhythmias (e.g., ventricular arrhythmia), markedly prolonged QT interval (corrected QTc ≥500 ms by Bazett's formula, as judged by the investigator);
- •Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), uncontrolled diabetes mellitus;
- •Pulmonary embolism, diffuse pulmonary infiltrates, impaired pulmonary function;
- •Other medical conditions deemed unsuitable for study participation by the investigator.
- •13. Anticipated or potential need for emergency treatment within 6 weeks due to ongoing or imminent oncologic emergencies (e.g., tumor mass effect, tumor lysis syndrome).
- •14. Primary immunodeficiency disorders.
- •15. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment requiring systemic anticoagulation therapy.
- •16. Any medical condition that may interfere with the assessment of safety or efficacy of the study treatment.
- •17. Live attenuated vaccines or mRNA vaccines administered within 8 weeks prior to lymphodepleting conditioning; inactivated vaccines administered within 4 weeks prior to lymphodepleting conditioning.
- •18. Females of childbearing potential who are pregnant or breastfeeding (Subjects with surgical sterilization or menopause for ≥2 years are not regarded as of childbearing potential).
- •19. Male or female participants unwilling to use contraceptive measures from the time of informed consent through 6 months after completion of study treatment.
- •20. Participants judged by the investigator to be unlikely to complete all study visits and procedures (including follow-up) or unable to comply with study participation requirements.
- •21. History of autoimmune disease within the past 2 years causing end-organ damage or requiring systemic immunosuppressive agents/systemic disease-modifying therapy (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.).
研究组 & 干预措施
GT737 Injection treatment group
Experimental
GT737 Injection
干预措施: GT737 Injection (Biological)
结局指标
主要结局
Proportion of participants experiencing dose limiting toxicity
时间窗: 28 days
The proportion of participants with dose-limiting toxicity (DLT) occurring within 28 days after infusion
Adverse Events (AEs) occurring after infusion and their proportions
时间窗: 28 days
Adverse Events (AEs) occurring after infusion and their proportions
Severity of Adverse Events (AEs) after infusion
时间窗: 28 days
Assess the severity of Adverse Events (AEs) within 28 days after infusion
Compare the differences in safety and tolerability between different treatment subgroups (monotherapy and combination with sirolimus).
时间窗: 28 Days
Difference in the incidence and severity of DLT among different treatment subgroups (monotherapy and combination with sirolimus)
次要结局
- Pharmacokinetic parameters: Time to peak expansion （Tmax）after GT737 infusion(28 Days)
- Pharmacokinetic parameters: peak expansion（Cmax） after GT737 infusion(28 Days)
- Pharmacokinetic parameters: area under the curve (AUC) after GT737 infusion(28 Days)
- Pharmacokinetic parameters: survival duration after GT737 infusion(12 months after infusion)
- Pharmacokinetic parameters: differences in Time to peak expansion （Tmax）of GT737 cells across different treatment subgroups(28 Days)
- Pharmacokinetic parameters: differences in peak expansion（Cmax）of GT737 cells across different treatment subgroups(28 Days)
- Pharmacokinetic parameters: differences in area under the curve (AUC) of GT737 cells across different treatment subgroups(28 Days)
- Pharmacokinetic parameters: differences in survival duration of GT737 cells across different treatment subgroups(12 months after infusion)
研究者
研究点 (1)
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