An Open-label, Multi-center Phase Ib/II Study of CN201 in Subjects With Precursor B-cell Acute Lymphoblastic Leukemia

This is an interventional treatment trial for Acute Lymphoblastic Leukemia Read More

Inclusion Criteria:

1. Subjects aged ≥18 years old on the day of signing the ICF.

2. Subjects with B-ALL (including pro B-, pre B-, common ALL) who have more than 5% blasts in the bone marrow will be enrolled into different cohorts according to the following criteria:

   1. Subjects with Ph-negative B-ALL with any of the following could be enrolled in Phase I and Cohort 1 in Phase II:

      • Refractory to primary induction therapy or salvage therapy
      • Relapse with first remission duration ≤12 months
      • Second or later relapse
      • Relapse after allogeneic HSCT
   2. Subjects with Ph-positive B-ALL who have progressed after or are intolerant to their second (or more) tyrosine kinase inhibitors (TKIs).
3. Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
4. At least 3 months expected survival.

5. Adequate organ function, further defined as:

   Liver Function Total bilirubin ≤1.5 × upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤3 × ULN Aspartate aminotransferase (AST) ≤3 × ULN Renal Function Serum/plasma creatinine, or Creatinine clearance ≤1.5 × ULN or

   • 50 mL/min (calculated by Cockcroft-Gault formula)
6. Female subjects must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception method from Screening until 90 (±7 days) days after the last dose of CN201.
7. Subjects must be able to understand and sign the paper ICF before any study-specific procedure is conducted.

Exclusion Criteria:

1. Subjects with Burkitt's leukemia.
2. Subjects who have received prior treatment with anti-CD19 therapy within 3 months prior to the first dose of CN201.
3. Subjects who have received allogeneic HSCT within 12 weeks prior to the first dose of CN201.
4. Subjects who have received autologous HSCT within 6 weeks prior to the first dose of CN201.
5. Subjects who have received radiotherapy or chemotherapy within 2 weeks, prior to the first dose of CN201 (except for intrathecal chemotherapy and dexamethasone).
6. Subjects who have received immunotherapy within 3 weeks prior to the first dose of CN201.
7. Subjects who have received other investigational agents (not yet approved by any regulatory agency) within 3 weeks prior to the first dose of CN201.
8. Subjects who have received prior treatment with CAR-T within 3 months prior to the first dose of CN201.
9. Subjects with major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks prior to the first dose of CN201, or elective surgery during the study.

10. Subjects who use of live attenuated vaccine within 4 weeks prior to the first dose of CN201

    • Exception: Use of an approved COVID-19 vaccine is allowed, but the last dose of COVID-19 vaccine must be administered at least 2 weeks prior to the first dose of CN201.
    • For active subjects enrolled in this study, COVID-19 vaccination is allowed after 8 weeks treatment have been completed and the safety data have been obtained, to allows conclusions regarding the safety of the CN201.
11. Subjects with adverse reactions prior to anti-tumor therapy that have not recovered to Grade ≤ 1 assessed by NCI-CTCAE Version 5.0 (except for toxicities such as alopecia judged by the Investigator as no safety risk).
12. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
13. Subjects with clinically symptomatic metastases to the central nervous system (CNS) or meninges, or other evidence of uncontrolled metastases to the CNS or meninges, judged by the Investigator. History CNS leukemia that is controlled with intrathecal therapy is allowed.
14. Subjects with active infection and in current need of, or likely to need, intravenous anti infective therapy.
15. Subjects with a history of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody.
16. Subjects with chronic infection with hepatitis B, defined as having a positive hepatitis B surface antigen (HBsAg) test and/or detectable level of HBV DNA at Screening, or hepatitis C infection, defined as having a positive HCV antibody test.
17. Subjects with current or previous interstitial lung disease.
18. Subjects with concomitant secondary malignancies (except adequately treated non melanomatous skin cancers, ductal carcinoma in situ, superficial bladder cancer, prostate cancer, or in situ cervical cancers) are excluded unless a complete remission is achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.

19. Subjects with a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

    • Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, or QTc interval ≥480 ms.
    • Acute coronary syndrome, congestive heart failure, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to the first dose of CN201.
    • New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) <50%.
20. Subjects with uncontrollable third space effusion, as judged by the Investigator.
21. Subjects with active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) or history of autoimmune disease with potential CNS involvement.
22. Any active acute Graft-versus-Host Disease (GvHD), Grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment.
23. Any systemic therapy against GvHD within 2 weeks before start of CN201.
24. Subjects who have previously received immunotherapy and experienced Grade ≥3 immune-related adverse events (irAEs).
25. Subjects with known alcohol or drug dependence.
26. Subjects with mental disorders or other conditions that pose high noncompliance risks in the opinion of the Investigator.
27. Subjects with any other condition or circumstance that would, in the opinion of the Investigator, make the subject unsuitable for participation in this clinical study.