A Dose-escalation Clinical Study of QH103 Cell Injection (CD19 CAR-γδT Cell Injection) in Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL).
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a single-arm, single-center, interventional, dose-escalation clinical study designed to evaluate the safety and tolerability of QH103 Cell Injection in the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia.
详细描述
To evaluate the safety and tolerability of QH103 Cell Injection in the treatment of relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia, and to evaluate dose-limiting toxicity and maximum tolerated dose.
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
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥14 years, gender is not limited;
- •Patients with clinically diagnosed relapsed/refractory B-ALL (except those presenting with extramedullary disease only), including any of the following:
- •Failure to obtain CR after 2 cycles of standard chemotherapy;
- •First induction of CR, but duration of CR is ≤12 months;
- •Relapsed/refractory B-ALL that has failed to respond to the first or multiple salvage treatments;
- •Relapse after hematopoietic stem cell transplantation, including hematological relapse and positive micro residual disease (MRD).
- •Cytological or histological confirmation of tumor cell immunophenotyping as CD19 positive;
- •Bone marrow with a ratio of ≥5% primitive/naïve lymphocytes (morphology);
- •Expected survival time of more than 3 months;
- •Eastern Cooperative Oncology Group (ECOG) score of 0-2;
- •Vital organ function meets the following requirements: left ventricular ejection fraction ≥50% on echocardiography; serum creatinine≤1.5 × upper limit of normal range (ULN); glutamine aminotransferase, aspartate aminotransferase ≤3 times ULN, total bilirubin ≤1.5 times ULN;
- •Pregnancy tests for women of childbearing age should be negative, and both men and women should agree to use effective contraception during treatment and for the following 1 year.
- •Toxicity of prior antitumor therapy ≤ grade 1 (according to CTCAE version 5.0) or acceptable inclusion/exclusion criteria level.
- •No significant hereditary disease;
- •Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;
- •Sign the trial informed consent form.
排除标准
- •with uncontrolled active central nervous system leukemia (CNSL) or a history of epilepsy, cerebrovascular disease
- •Pregnant or lactating women, or those who do not consent to the use of the drug during and within 1 year after treatment;
- •Other malignant tumors not in remission;
- •with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy;
- •Patients who have received immune cell therapy within 6 months prior to enrollment and donor lymphocyte infusion within 6 weeks prior to enrollment.
- •Patients with confirmed positive serum anti-FMC63 and DSA reactions;
- •Patients who have participated in other clinical trials within 4 weeks prior to enrollment;
- •Uncontrolled infectious or other serious diseases, including but not limited to infections (Human Immunodeficiency Virus, acute or chronic active hepatitis B or hepatitis C), congestive heart failure, unstable angina pectoris cardiac arrhythmias, or conditions that the attending physician considers to be an unpredictable risk;
- •Uncontrollable plasma fluid, such as large pleural effusions or ascites;
- •History of stroke or intracranial hemorrhage within 3 months prior to enrollment;
- •Major surgery or trauma within 28 days prior to enrollment, or major side effects from which you have not recovered;
- •History of allergy to any of the ingredients in the cellular product;
- •Inability to understand or unwillingness to sign the informed consent form;
- •Other reasons deemed by the investigator to be unsuitable for the clinical trial.
研究组 & 干预措施
Patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells
干预措施: QH103 Cell Injection (Biological)
Patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells
干预措施: Fludarabine (Drug)
Patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: First infusion date of QH103 cells to 28 days end cell infusion
DLT was defined as QH103 Cells-related events with onset within first 28 days following infusion: The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting \> 2 weeks; Any QH103 cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Incidence of Adverse Events (AEs)
时间窗: 12 months
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after QH103 infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0
Maximum tolerated dose (MTD)
时间窗: 28 days
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
次要结局
- Progression Free Survival (PFS)(12 months)
- Overall Survival (OS）(12 months)
- Pharmacokinetics: Persistence of the QH103 cells(28 days)
- Pharmacodynamics: Peak level of cytokines in serum(28 days)
- Overall Response Rate(ORR)(12 months)
研究者
Xiaoyu Zhu
Director of Hematology Department
Anhui Provincial Hospital