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

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

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.

Inclusion Criteria:

• 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:

  1. Aspartate aminotransferase (AST) ≤3 times the upper limit of normal (ULN);
  2. Alanine aminotransferase (ALT) ≤3 times ULN;
  3. Total bilirubin ≤2 times ULN (for patients with Gilbert's syndrome, total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN);
  4. Serum creatinine ≤1.5 times ULN, or creatinine clearance ≥60 mL/min (using the Cockcroft-Gault formula);
  5. International Normalized Ratio (INR) ≤1.5 times ULN and activated partial thromboplastin time (APTT) ≤1.5 times ULN;
  6. Left ventricular ejection fraction (LVEF) ≥50%;
  7. 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).

Exclusion Criteria:

• 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:

  1. HBsAg and/or HBeAg positive;
  2. HBe-Ab and/or HBc-Ab positive with HBV-DNA levels above the lower limit of quantification;
  3. HCV-Ab positive;
  4. TP-Ab positive;
  5. HIV antibody positive;
  6. 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:

  1. NYHA Class III or IV congestive heart failure;
  2. Severe arrhythmia requiring treatment;
  3. Uncontrolled hypertension or pulmonary hypertension despite standard therapy;
  4. Unstable angina;
  5. Myocardial infarction, bypass surgery, or stent placement within six months before cell retransfusion;
  6. Clinically significant valvular disease;
  7. 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.