Inaticabtagene Autoleucel (Inati-cel; CNCT19) Treatment for Newly Diagnosed B-cell ALL Patients in CR1

Clinical Study on Inaticabtagene Autoleucel (Inati-cel; CNCT19) Injection for Adolescents and Adults With B-Cell Acute Lymphoblastic Leukemia in First Complete Remission (CR1)

This investigator-initiated, prospective, single-arm, open-label, single-center phase II study aims to evaluate the long-term survival benefit and safety of a commercial CD19 CAR-T product in newly diagnosed Philadelphia chromosome-positive or negative (Ph-positive or Ph-negative) B-cell ALL patients who achieve CR1 after induction chemotherapy. A total of 20 patients will be enrolled in the study. The primary endpoints include disease-free survival (DFS) and overall survival (OS) rates after a median follow-up of 2 years, minimal residual disease (MRD) negativity rate, and the proportion of patients undergoing subsequent hematopoietic stem cell transplantation (HSCT). The frequency and severity of adverse events (AEs) and serious adverse events (SAEs) occurring after infusion will also be recorded.

Inclusion Criteria:

1. Age ≥14 years and ≤70 years at screening, with no restrictions on gender.

2. ECOG performance status of 0 to 1.

3. Newly diagnosed B-ALL within 12 months and achieving CR1 after standard induction chemotherapy. This includes B-ALL patients with <5% bone marrow blasts, no blasts in peripheral blood, and no extramedullary leukemia. Diagnosis and chemotherapy regimen follow the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2021 Edition).

4. At the time of B-ALL diagnosis, leukemia cells in bone marrow or peripheral blood confirmed as CD19-positive via flow cytometry.

5. Adequate organ function meeting the following criteria:

   1. Aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN).
   2. Alanine aminotransferase (ALT) ≤3× ULN.
   3. Total bilirubin ≤2× ULN (for patients with Gilbert's syndrome, total bilirubin ≤3.0× ULN and direct bilirubin ≤1.5× ULN).
   4. Serum creatinine ≤1.5× ULN, or creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula).
   5. International Normalized Ratio (INR) ≤1.5× ULN and activated partial thromboplastin time (APTT) ≤1.5× ULN.
   6. Minimum pulmonary reserve defined as ≤Grade 1 dyspnea and oxygen saturation >91% on room air.

6. No intent or eligibility for hematopoietic stem cell transplantation.

7. Meets the leukapheresis standards of the study center, with no contraindications for apheresis.

8. Women of childbearing potential must have a negative blood/urine pregnancy test during the Inati-cel screening period and before preconditioning (results within three days prior to preconditioning). All male and female patients of childbearing potential must agree to use effective contraception throughout the study and for at least two years following study treatment. A female is considered of childbearing potential if biologically capable of having children and engaging in regular sexual activity. Women are considered not of childbearing potential if they meet at least one of the following:

   1. History of hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.
   2. Medically confirmed ovarian failure.
   3. Postmenopausal (absence of menstruation for at least 12 consecutive months).

Exclusion Criteria:

1. Diagnosis of Burkitt lymphoma/leukemia, heterozygous or double-hit leukemia, or chronic myeloid leukemia in blast crisis.

2. Presence of ≥5% blasts in the bone marrow or peripheral blood, or evidence of extramedullary leukemia before screening or preconditioning.

3. Prior treatment with CAR-T cell therapy or hematopoietic stem cell transplantation (HSCT) before screening or preconditioning.

4. Genetic syndromes associated with bone marrow failure, including Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other known bone marrow failure syndromes.

5. Presence of any of the following conditions:

   1. Positive for HBsAg and/or HBeAg.
   2. Positive for HBe-Ab and/or HBc-Ab with HBV-DNA levels above the detectable threshold.
   3. Positive for HCV-Ab.
   4. Positive for TP-Ab.
   5. EBV-DNA or CMV-DNA levels above the detectable threshold.
   6. Positive for HIV antibodies.

6. Diagnosis of other malignancies within the past 5 years, unless the tumor was curatively treated, with a follow-up period exceeding 5 years, and a low risk of recurrence as assessed by the investigator.

7. Presence of any of the following cardiac conditions:

   1. Left ventricular ejection fraction (LVEF) ≤45%.
   2. Congestive heart failure classified as NYHA class III or IV.
   3. Severe arrhythmias requiring treatment or clinically significant conduction abnormalities on ECG, including QTc ≥480 ms (QTcB = QT/RR^1/2).
   4. Uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg) or pulmonary hypertension despite standard treatment.
   5. Unstable angina.
   6. Myocardial infarction or coronary artery bypass/stent surgery within the past 6 months.
   7. Clinically significant valvular disease.
   8. Other cardiac conditions deemed unsuitable for study enrollment by the investigator.

8. History of epilepsy, ischemic or hemorrhagic stroke, cerebellar disease, or other active central nervous system disorders.

9. Clinically significant pleural effusion at the time of screening.

10. History of deep vein thrombosis or pulmonary embolism within the past 6 months.

11. Known hypersensitivity to any components of the investigational products used in the trial.

12. Receipt of live vaccines within 6 weeks prior to screening.

13. Presence of active infections at the time of screening.

14. An expected survival of less than 3 months.

15. Participation in other interventional clinical studies involving investigational drugs:

    1. For investigational drugs not yet approved, the last dose administered less than 3 months before cell infusion.
    2. For approved drugs, the last dose administered less than 5 half-lives before cell infusion.

16. Any other conditions deemed unsuitable for study participation by the investigator.