Inaticabtagene Autoleucel (Inati-cel; CNCT19) Treatment for MRD-Positive B-ALL Patients in CR1

Официальное название

A Clinical Study of Inaticabtagene Autoleucel (Inati-cel; CNCT19) Treatment for B-Cell Acute Lymphoblastic Leukemia(B-ALL) Patients in First Complete Remission (CR1)，Minimal Residual Disease(MRD) Positive

Обзор

This investigator-initiated, prospective, single-arm, open-label, single-center clinical study aims to evaluate the efficacy and safety of Inaticabtagene autoleucel (Inati-cel;CNCT19)CD19 CAR-T theraphy in adults B-ALL that are in first complete remission(CR1) with minimal residual disease (MRD) positivity. This trial will enroll 20 participants for leukapheresis and treatment with lymphodepleting chemotherapy followed by Inati-cel CAR T cell infusion. Patients will be assessed for MRD negativity rate(at months 1, 2, 3, and 6 after CAR-T transfusion), duration of MRD negativity, overall survival(OS), relapse-free survival(RFS), pharmacokinetics(PK) characteristics, incidence of adverse events(AEs), exploratory biomarker research at 1,2,3,6,9,12,15,18,21 and 24- months post Inati-cel infusion.

Вмешательства

• Биопрепарат single dose of Inaticabtagene autoleucel
  Inaticabtagene autoleucel will be transfusioned intravenously at the recommended dose of 0.5×10\^8 (ranging 0.2-0.6×10\^8) viable CAR-T cells. If the quantity of CAR-T cells of the patient is sufficient, after the patient receives the first CAR-T transfusion 5\~6 months，they will receive a second CAR-T cell transfusion. The aim of the second transfusion is to prolong the duration of CAR-T in the patient's body and prolong the patient's DOR. The dose and procedures of the second transfusion are

Первичные конечные точки

• MRD negativity rate [Срок оценки: up to 24 months]

Вторичные конечные точки (6)

• Duration of MRD negativity [Срок оценки: till the end of the study, up to 5 years]
• Relapse-free survival (RFS) [Срок оценки: till the end of the study, up to 5 years]
• Overall survival (OS) [Срок оценки: till the end of the study, up to 5 years]
• incidence of adverse events [Срок оценки: up to 24 months]
• Pharmacokinetics characteristics of Inati-cel [Срок оценки: till the end of the study, up to 5 years]
• exploratory biomarker research [Срок оценки: till the end of the study, up to 5 years]

Критерии участия

Критерии включения

• Age between ≥16 and ≤70 years at screening, no gender restrictions
• ECOG score of 0-1 at screening
• Newly diagnosed Ph-negative B-ALL, MRD positive(bone marrow MRD ≥0.01% by flow cytometry) in CR1 (with <5% blasts in bone marrow, no blasts in peripheral blood, no extramedullary disease)after induction chemotherapy or consolidation chemotherapy.
• Newly diagnosed Ph-positive B-ALL, MRD positive(bone marrow MRD ≥0.01% by flow cytometry or BCR-ABL1 >0.01% detected by qPCR) in CR1 (with <5% blasts in bone marrow, no blasts in peripheral blood, no extramedullary disease) .
• At diagnosis of B-ALL,CD19 expression of leukemic cells is positive by flow cytometry in bone marrow or peripheral blood.
• Appropirate organ function, meeting the following criteria:

• Aspartate aminotransferase (AST) ≤3 times the upper limit of normal (ULN);
• Alanine aminotransferase (ALT) ≤3 times ULN;
• Total bilirubin ≤2 times ULN (for patients with Gilbert's syndrome, total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN);
• Serum creatinine ≤1.5 times ULN, or creatinine clearance ≥60 mL/min (using the Cockcroft-Gault formula);
• International Normalized Ratio (INR) ≤1.5 times ULN and activated partial thromboplastin time (APTT) ≤1.5 times ULN;
• Left ventricular ejection fraction (LVEF) ≥50%;
• Minimum pulmonary reserve, with oxygen saturation >91% on room air;
• Meets leukapheresis standard of the study center, with no contraindications for blood cell separation;
• Voluntarily agrees to participate in this study and signs on the informed consent form(ICF).

Критерии исключения

• Received CAR-T cell therapy before screening;
• Inherited bone marrow failure syndrome(IBMFS) or any other known bone marrow failure syndromes;
• Active systemic autoimmune diseases requiring treatment;
• Any of the following conditions:

• HBsAg and/or HBeAg positive;
• HBe-Ab and/or HBc-Ab positive with HBV-DNA levels above the lower limit of quantification;
• HCV-Ab positive;
• TP-Ab positive;
• HIV antibody positive;
• EBV-DNA or CMV-DNA levels above the lower limit of quantification;
• Active infection at screening.
• Any other malignancy within the past five years before screening, excluding cases where the patient has been disease-free for more than 5 years after curative treatment or has a low risk of relapse as assessed by the investigator;
• Any of the following cardiac conditions:

• NYHA Class III or IV congestive heart failure;
• Severe arrhythmia requiring treatment;
• Uncontrolled hypertension or pulmonary hypertension despite standard therapy;
• Unstable angina;
• Myocardial infarction, bypass surgery, or stent placement within six months before cell retransfusion;
• Clinically significant valvular disease;
• Other cardiac conditions deemed unsuitable by the investigator;
• History of epilepsy, cerebellar disease, or other active central nervous system disorders;
• Uncontrolled diabetes;
• History of symptomatic deep vein thrombosis or pulmonary embolism within six months before screening that is not well controlled;
• History of hypersensitivity to any component of the investigational product.
• Received a live vaccine within six weeks before screening;
• Life expectancy of less than three months;
• Participation in another interventional clinical trial and receiving investigational drugs within three months (for unapproved drugs) or within five half-lives (for approved drugs) before cell infusion, or plans to participate in another clinical trial or receive anti-cancer therapy outside the study protocol during the study period;
• Other conditions deemed unsuitable for participation in this clinical trial by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT06718244 · (2024) Ruijin Ethics No.447

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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