A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)

A Phase Ib/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of CNCT19 in Children and Adolescent(Pediatric) Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)

This is a multi-center, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 treatment in Children and Adolescent (pediatric) patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-cell ALL).

This trial is a multi-center, open label, single-arm, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 in Children and Adolescent(aged 3~18 years old) patients (pediatric) with r/r B-cell ALL.

The phase Ib part of the trial is to evaluate the safety, optimal dose of CNCT19, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Children and Adolescent patients with r/r B-cell ALL.

The phase II part of the trial is to evaluate the efficacy and safety of CNCT19 in in the treatment of Children and Adolescent patients with r/r B-cell ALL.

The study includes screening, pre-treatment (Cell Product manufacture & lymphodepletion), CNCT19 infusion , safety and efficacy follow-up, and survival follow-up. All subjects who have received CNCT19 infusion will be followed for up to 2 years.

Key Inclusion Criteria:

1. Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian)
2. Age 3 to 18. Weight ≥10kg
3. Relapsed or refractory acute lymphoblastic leukemia (ALL).
4. Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening.
5. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
6. Karnofsky (age ≥ 16 years) performance status ≥ 70 or Lansky (age < 16 years) performance status ≥ 50 at screening
7. Organ function requirements: All patients must have adequate renal and liver functions

Key Exclusion Criteria:

1. Active Central Nervous System (CNS) involvement by malignancy.

2. Isolated extra-medullary disease relapse.

3. Patients with Burkitt's lymphoma/leukemia, mixed phenotypic acute leukemia and Chronic Myelogenous Leukemia in Blast Crisis

4. History of concomitant genetic syndrome

5. Patients with acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks before screening.

6. Active systemic autoimmune disease

7. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive).

8. Patients with active infections at screening.

9. Patients who received specified chemotherapy before CNCT19 infusion

10. Radiotherapy before CNCT19 infusion:

    Non-CNS site of radiation completed < 4 weeks prior to CNCT19 Infusion; CNS directed radiation completed < 8 weeks prior to CNCT19 infusion.

11. Donor lymphocyte infusion (DLI) must be stopped > 6 week prior to CNCT19 infusion.

12. Has had treatment with any prior CAR-T therapy.

13. Life expectancy < 3 months.