2023-509212-29-01招募中2 期
CARLA-M19 : “Prospective non-randomized phase I/II study investigating the safety of CD19 CAR-T cells in patients with refractory/relapsed AML expressing CD19.”
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of patients deceased without progression at one month after CAR T-cell infusion. Non-progression mortality (NPM). NPM is defined as death occurred in patients without evidence of AML progression. Absence of response, progression or relapse of AML define progression status
研究概览
简要总结
To investigate the safety and tolerability of the administration of academically produced CD19 CAR-T cells.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- •Creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL/min
- •Serum ALT/AST ≤ 2.5 upper limit of normal (ULN).
- •Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s syndrome
- •Cardiac ejection fraction ≥ 45 %.
- •No clinically significant electrocardiogram (ECG) findings
- •No clinically significant pleural effusion
- •Baseline oxygen saturation > 92 % on room air
- •Female patients of childbearing potential must: a. have a negative pregnancy test (blood) at screening visit. b. either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the CAR-T cell infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled. c. Agree to abstain from breast feeding during the study participation and for 1 year after the CAR-T cell infusion. Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after the CAR-T cell infusion, even if he has undergone a successful vasectomy.
- •Patient with AML that expresses CD19 by Flow-cytometry
- •Patients with R/R AML defined as: • Primary refractory: absence of remission after two courses of induction chemotherapy, • Secondary refractory: absence of remission after salvage treatment in relapsing patients, • Post-transplant relapse in patients having had allo-HCT
- •Eastern Cooperative Oncology Group (ECOG) performance status of < 2
- •Estimated life expectancy of > 2 months
- •Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) involvement
- •Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia).
- •Platelet count ≥ 30000/uL.
- •Absolute lymphocyte count ≥ 200/uL
排除标准
- •Patient unable to sign the informed consent
- •Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid (CSF) malignant cells or brain metastases
- •History or presence of non-malignant CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- •Patient placed under guardianship or curatoship
- •Females either pregnant/breast-feeding or planning to become pregnant
- •Absence of medical insurance cover
- •Patient with R/R AML that does not expresses CD19
- •History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease-free and without anticancer therapy for at least 3 years
- •Prior CD19 targeted therapy
- •Prior CAR therapy or other genetically modified T cell therapy
- •Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management
- •History of human immunodeficiency virus (HIV) or HTLV1
- •Infection or acute or chronic active hepatitis C infection
- •Infection or acute or chronic active hepatitis (Hep) B. Subjects with history of Hep B or Hep C infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines
结局指标
主要结局
Number of patients deceased without progression at one month after CAR T-cell infusion. Non-progression mortality (NPM). NPM is defined as death occurred in patients without evidence of AML progression. Absence of response, progression or relapse of AML define progression status
Number of patients deceased without progression at one month after CAR T-cell infusion. Non-progression mortality (NPM). NPM is defined as death occurred in patients without evidence of AML progression. Absence of response, progression or relapse of AML define progression status
次要结局
- Number of patients with manufacturing failure and out of specification (OOS) deviation
- Duration of CAR-T cell persistence in blood after infusion evaluated by flow-cytometry and PCR
- Number of patients with overall response at one-month
- Response duration, and number of patients alive at 3, 6 and 12 months
- Number of patients alive without relapse at 3, 6 and 12 months
- Number of deaths without progression at 3, 6 and 12 months
- Number of patients with complete remission (CR) at 1 and 3 months
研究者
Professor Ibrahim YAKOUB-AGHA
Scientific
Centre Hospitalier Universitaire De Lille
研究点 (1)
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