precursor B-cell acute lymphoblastic leukemia (B-ALL)
Conditions
Interventions
target dose 600µg/ time group:During the treatment period, subjects will receive an intravenous (IV) infusion of CN201 once a week (QW) in a 4-week treatment cycle.
target dose 1200µg/ time group:During the treatment period, subjects will receive an intravenous (IV) infusion of CN201 once a week (QW) in a 4-week treatment cycle.
target dose 2500µg/ time group:During the treatment period, subjects will receive an intravenous (IV) infusion of CN201 once a week (QW) in a 4-week treatment cycle.
target dose 5000µg/ time group:During the treatment period, subjects will receive an intravenous (IV) infusion of CN201 once a week (QW) in a 4-week treatment cycle.
Sponsors
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 at the time of signing the informed consent. 2. B-ALL patients with more than 5% of the original lymphocytes in the bone marrow meet one of the following conditions: (1) Ph-B-ALL subjects have any of the following conditions: 1) Complete remission was not achieved after initial induction therapy; 2) No complete remission was achieved after salvage therapy after recurrence; 3) Relapse within 12 months after the first remission; 4) Secondary or more recurrence; 5) Recurrence after hematopoietic stem cell transplantation. (2) B-ALL subjects with Ph+ : those who met the above criteria after treatment with at least two or more tyrosine kinase inhibitors (TKI); Or, there are T315I mutants. 3. ECOG physical strength score =50 mL/min (as calculated by Cockcroft-Gault formula); (3) Cardiopulmonary function: 1) Echocardiography: left ventricular ejection fraction (LVEF) >= 50%, centerless fluid; 12-lead electrocardiogram (ECG) results: No clinically significant ECG abnormality [atrial fibrillation of any grade, degree II type II atrioventricular block or degree III atrioventricular block, or QTcF > 470 msec (female) or > 450 msec (male); other uncontrolled symptomatic arrhythmias]; 2) Blood oxygen saturation > 92% (in non-oxygen state). 6. Fertile female subjects must not be pregnant, not breastfeeding, and agree to remain abstinent (abstain from heterosexual intercourse) or use a highly effective dual contraceptive method from screening until 90 (±7) days after the last dose of CN201. During that time, women are not allowed to donate their eggs. Dual contraception is defined as a condom and one of the following: (1) Hormonal contraception (including oral contraceptives, long-acting hormone implantation, hormone injection); (2) Vaginal ring or intrauterine device; (3) Documented surgical sterilization at least 6 months prior to screening (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy or bilateral oophorectomy for women and vasectomy for men [appropriate documentation of absence of sperm in semen after vasectomy is required], provided the male partner is the sole partner); (4) Women with no reproductive potential must be at least 12 months after menopause. Postmenopausal status will be confirmed by testing follicle-stimulating hormone (FSH) levels, 40 IU/L at screening in amenorrhea subjects. Women who do not have sex with the opposite sex are also eligible; (5) Periodic abstinence (e.g. calendar, ovulation, symptomatic fever, post-ovulation methods) and withdrawal are not very effective contraceptive methods. Complete abstinence during the study period and 90 days after the last study treatment is acceptable; (6) Female subjects in same-sex relationships were not required to use contraception. Male subjects must be willing to agree to remain abstinent (abstain from heterosexual intercourse) or use a highly effective contraceptive method and to refrain from sperm donation throughout the study period and for 90 days after the last administration of CN201. 7. Subject must be able to fully understa
Exclusion criteria
Exclusion criteria: 1. Subjects with Burkitts 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 have received live attenuated vaccine within the four weeks prior to the initial use of the experimental medicinal product are specified as follows: (1) 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. (2) 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, Parkinsons disease, cerebellar disease, organic brain syndrome, or psychosis. 13. Subjects with central nervous system (CNS) infiltration. Subjects with a history of central nervous system infiltration that has been controlled by intrathecal injection are admitted. 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 uncontrollable third space effusion, as judged by the investigator. 20. Subjects with active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) or history of autoimmune disease with potential CNS involvem
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall frequency and severity of adverse events (AE);Incidence of DLTs;Dose-limit toxicity (DLT);Phase II recommended dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK characteristics;Changes of pharmacokinetic markers after administration;The number and percentage of patients who developed drug-resistant antibodies (ADA);CR/ CR(CRi) rate of incomplete hematological recovery within 2 cycles of treatment with CN201;Rate of complete MRD response;Rate of red blood cell and platelet transfusion independence; | — |
Countries
China
Contacts
Public ContactWang Jianxiang
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Outcome results
None listed